A Multi-center, Open-label, Randomized, Study to Assess the Onset of Platelet Aggregation Inhibition After a Single Subcutaneous Injection of ACT-246475 in Adults With Acute Myocardial Infarction
Phase: PHASE2
Conditions: Acute Myocardial Infarction
Sponsor: Viatris Innovation GmbH

Protocol: 
ID-076A202 
Official Title: 
A multi-center, open-label, randomized, study to assess the onset of platelet aggregation 
inhibition after a single subcutaneous injection of ACT-246475 in adults with acute myocardial 
infarction 
ClinicalTrials.gov Identifier:
NCT03487445 
Document date: 
19 July 2021

 
 
 
 
A C T- 2 4 6 4 7 5  
C or o n ar y arter y d ise ase 
Pr ot oc ol I D-0 7 6 A 2 0 2  
A m ulti -ce nter, o pe n -l a bel, r a n d o mize d , st u d y t o assess t he o nset of pl atelet 
a g gre g ati o n i n hi biti o n after a si n gle s u bc ut a ne o us i njecti o n of A C T - 2 4 6 4 7 5 i n a d ults 
wit h ac ute m y oc a r di al i nf arcti o n  
 
 
St u d y P has e:  
2 
E u dra C T N u m ber: 
2 0 1 8- 0 0 0 7 6 5- 3 6 
Stat us a n d versi o n: 
F i nal Versi o n  2 
Date:  
1 1 A pril 2 0 1 8 
D oc u me nt t y p e: 
A me n de d Gl o bal Pr ot oc ol 
I d orsia d oc u me nt n u m ber ( D oc N o.):  
D- 1 8. 0 7 8 
 
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, es peciall y u n p u blis he d data, is t he pr o pert y of t he s p o ns or of 
t his  st u d y, I d orsia P har mace uticals  Lt d.  It  is  t heref ore  pr o vi de d  t o  y o u  i n  c o nfi de nce  as  a n  i n vesti gat or, 
p ote nti al  i n vesti gat or,  or  c o ns ulta nt,  f or  re vie w  b y  y o u,  y o ur  pers o n nel,  a n d  a n  i n de pe n de nt  et hics 
c o m mittee or i nstit uti o nal re vi e w b oar d. It is u n derst o o d t hat t his i nf or mati o n will n ot be discl ose d t o ot hers 
wit h o ut  writte n  a ut h orizati o n  fr o m I d orsia P har mace uticals  Lt d,  e xce pt  t o  t he  e xte nt  necessar y  t o  o btai n 
i nf or me d c o nse nt fr o m t h ose p ers o ns t o w h o m t he st u d y treat me nt ma y be a d mi nistere d. 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 2 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
S P O N S O R C O N T A C T D E T AI L S 
S p o ns or  
 
I d orsia P har mace uticals Lt d  
He ge n hei mer matt we g 9 1  
C H - 4 1 2 3 Allsc h wil 
S witzerla n d  
 
+ 4 1 5 8 8 4 4 0 0 0 0  
Cli nical Trial P h ysicia n  
C o ntact details of t he Cli nical Trial P h ysi cia n ca n 
be f o u n d i n t he I n vesti gat or Site File 
Me dical E mer ge nc y H otli ne  
T oll tele p h o ne n u m ber: 
Site -s pecific  t oll  tele p h o ne  n u m bers  a n d  t oll-free 
n u m bers  f or  t he  M e dical E mer ge n c y H otli ne  ca n 
be f o u n d i n t he I n vesti gat or Site File  
 
S P O N S O R C O N T RI B U T O R S T O T H E P R O T O C O L 
Cli nical Trial Scie ntist  
 
Cli nical Trial Statisticia n  
 
Cli nical Trial P h ysicia n  
 
Cli nical Trial P har mac ol o gist  
 
Dr u g Safet y P h ysicia n  
 
 
 
C O N T R A C T R E S E A R C H O R G A NI Z A TI O N S I N F O R M A TI O N 
S o me  acti vities  will  be  dele gat e d  t o C o ntract Researc h  Or ga nizati o ns . A  list  of 
site-s pecific c o ntact details ca n be f o u n d i n t he I n v esti gat or Site File. 
 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 4 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
I N V E S TI G A T O R SI G N A T U R E P A G E 
S t u d y title 
A m ulti -ce nter, o pe n -la b el, ra n d o mize d, st u d y t o assess t he o nset of platelet a g gre gati o n 
i n hi biti o n  after a  si n gle  s u bc uta ne o us  i njecti o n  of  A C T -2 4 6 4 7 5  i n  a d ults  wit h  ac ute 
m y ocar dial i nfarcti o n  
 
I a gree t o t he ter ms a n d c o n diti o ns relati n g t o t his st u d y as d efi ne d i n t his pr ot oc ol a n d 
a n y  ot her  pr ot oc ol -r elate d  d oc u me nts.  I  f ull y  u n dersta n d  t hat  a n y  c ha n ges  i nstit ute d  b y 
t he  i n vesti gat or(s)  wit h o ut  pre vi o us  a gree me nt  wit h  t he  s p o ns or  w o ul d  c o nstit ute  a 
pr ot oc ol  de viati o n,  i n cl u di n g  a n y  a ncillar y  st u di es  or  pr oce d ures  perf or me d  o n  st u d y 
s u bjects ( ot her t ha n t h ose pr oce d ures necessar y f or t he well bei n g of t he s u bj ects). 
 
I  a gr ee t o c o n d uct t his st u d y i n  acc or da n ce  wit h t he  Declarati o n of  Helsi n ki pri nci ples, 
I nter nati o nal C o u ncil f or Har m o nisati o n (I C H) G o o d Cli nical Practice ( G C P) g ui deli nes, 
a n d a p plica ble re g ulati o ns a n d la ws. 
 
Pri nci p al 
I n vesti g at or 
C o u ntr y  
Site 
n u m ber  
T o w n  
D ate  
 
Si g n at ure  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 5 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
T A B L E O F C O N T E N T S 
S P O N S O R C O N T A C T D E T A I L S ...................................................................................... 2 
S P O N S O R C O N T RI B U T O R S T O T H E P R O T O C O L  ....................................................... 2 
C O N T R A C T R E S E A R C H O R G A NI Z A TI O N S I N F O R M A T I O N ................................... 2 
LI S T O F A B B R E VI A TI O N S A N D A C R O N Y M S  .......................................................... 1 1 
N O N -S U B S T A N TI A L G L O B A L A M E N D M E N T 1  ....................................................... 1 3 
P R O T O C O L S Y N O P SI S I D - 0 7 6 A 2 0 2 ............................................................................. 1 4 
1  
B A C K G R O U N D ......................................................................................................... 2 1  
1. 1  
Pre -h os pital treat me nt of ac ute m y ocar dial i nfarcti o n  ................................. 2 1 
1. 2  
St u d y treat me nt ( A C T - 2 4 6 4 7 5) .................................................................... 2 1 
1. 2. 1  
N o ncli nical data  ................................................................................ 2 2 
1. 2. 2  
Effects i n h u ma ns .............................................................................. 2 3  
1. 2. 2. 1  
St u d y A C - 0 7 5- 1 0 1 ................................................................. 2 3 
1. 2. 2. 2  
St u d y A C - 0 7 6- 1 0 1 ................................................................. 2 3 
1. 2. 2. 3  
St u d y A C - 0 7 6- 1 0 2 ................................................................. 2 4 
1. 3  
P ur p ose a n d rati o nale of t he st u d y ................................................................ 2 5  
1. 4  
S u m mar y of k n o w n a n d p ote ntial ris ks a n d be nefits .................................... 2 5  
1. 4. 1  
P ote ntial ris ks relate d t o st u d y treat me nt a d mi nistrati o n  .................. 2 5 
1. 4. 2  
I nterfere n ce wit h oral P 2 Y1 2 rece pt or a nta g o nists ............................ 2 6 
1. 4. 3  
I n cl usi o n of v ul nera bl e s u bjects ....................................................... 2 7 
1. 4. 4  
P ote ntial ris ks ass ociate d wit h st u d y -s pecific pr oce d ures ................ 2 7 
1. 4. 5  
P ote ntial be nefits  ............................................................................... 2 8 
1. 4. 6  
O verall be n efit ris k assess me nt  ......................................................... 2 8 
2  
S T U D Y O BJ E C TI V E S  ............................................................................................... 2 8 
2. 1  
Pri mar y o bjecti ve  .......................................................................................... 2 8 
2. 2  
Ot her o bjecti ves  ............................................................................................ 2 9 
3  
O V E R A L L S T U D Y D E SI G N  A N D P L A N  ............................................................... 2 9 
3. 1  
St u d y d esi g n  ................................................................................................. 2 9 
3. 1. 1  
St u d y p eri o ds .................................................................................... 2 9  
3. 1. 2  
St u d y d urati o n ................................................................................... 3 0  
3. 2  
St u d y d esi g n rati o nale .................................................................................. 3 0  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 6 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
3. 3  
St u d y c o m mittees  ......................................................................................... 3 1 
4  
S U BJ E C T P O P U L A TI O N  .......................................................................................... 3 1 
4. 1  
S u bject p o p ulati o n descri pti o n ..................................................................... 3 1  
4. 2  
Rati o nale f or t he sel ecti o n of t he st u d y p o p ulati o n ...................................... 3 1  
4. 3  
I n cl usi o n criteria ........................................................................................... 3 2 
4. 4  
E x cl usi o n criteria  .......................................................................................... 3 2 
5  
T R E A T M E N T S  .......................................................................................................... 3 3 
5. 1  
St u d y treat me nt  ............................................................................................. 3 3 
5. 1. 1  
I n v esti gati o nal treat me nt ( A C T- 2 4 6 4 7 5): Des cri pti o n a n d 
rati o nale ............................................................................................ 3 3 
5. 1. 2  
St u d y treat me nt s u p pl y ..................................................................... 3 4  
5. 1. 2. 1  
St u d y treat me nt pac ka gi n g a n d l a beli n g  ................................ 3 4 
5. 1. 2. 2  
St u d y treat me nt distri b uti o n a n d st ora ge ................................ 3 4  
5. 1. 2. 3  
St u d y treat me nt ret ur n a n d destr ucti o n .................................. 3 5  
5. 1. 3  
St u d y treat me nt assi g n m e nt a n d dis pe nsi n g ..................................... 3 5  
5. 1. 3. 1  
St u d y treat me nt assi g n m e nt  .................................................... 3 5 
5. 1. 3. 2  
St u d y treat me nt dis pe nsi n g .................................................... 3 5  
5. 1. 4  
St u d y treat me nt pre parati o n a n d a d mi nistrati o n  ............................... 3 6 
5. 1. 5  
Bli n di n g ............................................................................................ 3 7  
5. 1. 6  
U n bli n di n g ........................................................................................ 3 7  
5. 1. 7  
St u d y treat me nt acc o u nta bilit y a n d c o m plia nce wit h st u d y 
treat me nt ........................................................................................... 3 7 
5. 1. 7. 1  
St u d y treat me nt acc o u nta bilit y  ............................................... 3 7 
5. 1. 7. 2  
St u d y treat me nt c o m plia nce  ................................................... 3 7 
5. 1. 8  
St u d y treat me nt d ose a dj ust me nts a n d i nterr u pti o ns ........................ 3 7  
5. 1. 9  
Pre mat ure disc o nti n uati o n of st u d y treat me nt  .................................. 3 7 
5. 1. 1 0  
St u d y- s pecific criteria f or i nterr u pti o n / pre mat ure 
disc o nti n uati o n of st u d y treat me nt .................................................... 3 8  
5. 2  
Pre vi o us a n d c o nc o mita nt t hera p y ................................................................ 3 8  
5. 2. 1  
Defi niti o ns  ........................................................................................ 3 8 
5. 2. 2  
Re p orti n g of pre vi o us/c o nc o mita nt t hera p y ..................................... 3 8  
5. 2. 3  
All o we d c o nc o mita nt t hera p y ........................................................... 3 8  
5. 2. 4  
F or bi d de n c o nc o mita nt t hera p y ........................................................ 3 9  
6  
S T U D Y E N D P OI N T S  ................................................................................................ 3 9 
6. 1  
Efficac y e n d p oi nts ........................................................................................ 3 9  
6. 2  
P har mac o ki netic a n d p h ar mac o d y na mic e n d p oi nts ..................................... 3 9  
6. 2. 1  
P har mac o d y na mic e n d p oi nts  ............................................................ 3 9 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 7 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
6. 2. 2  
P har mac o ki netic e n d p oi nts ............................................................... 3 9  
6. 3  
Safet y e n d p oi nts  ........................................................................................... 3 9 
7  
VI SI T S C H E D U L E A N D S T U D Y A S S E S S M E N T S  ................................................ 4 0 
7. 1  
St u d y visits  ................................................................................................... 4 0 
7. 1. 1  
Scree ni n g/re -scree ni n g ...................................................................... 4 0 
7. 1. 2  
U nsc he d ule d visits ............................................................................ 4 0  
7. 2  
St u d y assess me nts  ......................................................................................... 4 2 
7. 2. 1  
De m o gra p hics / bas eli ne c haracteristics  ........................................... 4 2 
7. 2. 2  
Efficac y assess me nts  ......................................................................... 4 3 
7. 2. 3  
P har mac o ki netic a n d p h ar mac o d y na mic assess me nts  ...................... 4 3 
7. 2. 3. 1  
P har mac o ki netic ass ess me nts  ................................................. 4 3 
7. 2. 3. 2  
P har mac o d y na mic assess me nts  .............................................. 4 3 
7. 2. 4  
Safet y assess me nts  ............................................................................ 4 4 
7. 2. 4. 1  
P h ysical e x a mi nati o n  .............................................................. 4 4 
7. 2. 4. 2  
Vital si g ns  ............................................................................... 4 5 
7. 2. 4. 3  
Wei g ht a n d hei g ht .................................................................. 4 5  
7. 2. 5  
La b orat or y assess me nts  .................................................................... 4 5 
7. 2. 5. 1  
T y pe of la b orat or y .................................................................. 4 5  
7. 2. 5. 2  
La b orat or y tests  ...................................................................... 4 6 
8  
S T U D Y C O M P L E TI O N A N D  P O S T -S T U D Y T R E A T M E N T/ M E DI C A L 
C A R E  .......................................................................................................................... 4 6 
8. 1  
St u d y c o m pleti o n  .......................................................................................... 4 6 
8. 2  
Pre mat ure wit h dra wal fr o m st u d y  ................................................................ 4 6 
8. 3  
Pre mat ure ter mi nati o n or s us pe nsi o n of t he st u d y ........................................ 4 7  
8. 4  
Me dical care of s u bj ects after st u d y c o m pleti o n / wit h dra wal fr o m 
st u d y .............................................................................................................. 4 7 
9  
S A F E T Y D E FI NI TI O N S A N D R E P O R TI N G R E Q UI R E M E N T S  ........................... 4 8 
9. 1  
A d verse e ve nts  .............................................................................................. 4 8 
9. 1. 1  
Defi niti o n of a d vers e e v e nts ............................................................. 4 8  
9. 1. 2  
Defi niti o ns of seri o us a d verse e v e nts ............................................... 4 8  
9. 1. 3  
Defi niti o n of s us pecte d u ne x pecte d seri o us a d vers e reacti o n .......... 4 9  
9. 1. 4  
Defi niti o n of treat me nt -e mer ge nt a d verse e v e nt  .............................. 4 9 
9. 1. 5  
I nte nsit y of a d vers e e ve nts  ................................................................ 4 9 
9. 1. 6  
Relati o ns hi p t o st u d y treat me nt  ........................................................ 5 0 
9. 1. 7  
Relati o ns hi p t o pr ot oc ol- ma n date d pr oce d ure .................................. 5 0  
9. 2  
Ti me peri o d a n d fre q ue n c y f or A E/ S A E ass ess me nt a n d f oll o w- u p ............ 5 0  
9. 2. 1  
F oll o w- u p of a d v erse e ve nts ............................................................. 5 0  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 8 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
9. 2. 2  
F ol l o w- u p of seri o us a d v erse e v e nts ................................................. 5 0 
9. 3  
Re p orti n g pr o ce d ures .................................................................................... 5 0  
9. 3. 1  
Re p orti n g of a d vers e e ve nts .............................................................. 5 0  
9. 3. 2  
A d diti o nal re p orti n g pr oce d ures f or seri o us a d v ers e e ve nts ............. 5 1  
9. 3. 3  
A d diti o nal re p orti n g pr oce d ures f or s us pecte d u n e x pecte d 
seri o us a d vers e reacti o ns .................................................................. 5 2 
9. 4  
Re p orti n g of st u d y treat me nt o ver d ose, mis use, a b use a n d err ors ............... 5 2  
9. 5  
St u d y s afet y m o nit ori n g  ................................................................................ 5 2 
1 0  S T A TI S TI C A L M E T H O D S  ....................................................................................... 5 2 
1 0. 1  
A nal ysis sets  ................................................................................................. 5 2 
1 0. 1. 1  
Scree ne d a nal ysis se t ........................................................................ 5 2 
1 0. 1. 2  
Ra n d o mize d a nal ysis set  ................................................................... 5 2 
1 0. 1. 3  
F ull a nal ysis set  ................................................................................. 5 3 
1 0. 1. 4  
M o difie d F ull a nal ysis set ................................................................. 5 3  
1 0. 1. 5  
Per -pr ot oc ol a n al ysis set  ................................................................... 5 3 
1 0. 1. 6  
Safet y s et  ........................................................................................... 5 3 
1 0. 1. 7  
Ot her a nal ysis sets  ............................................................................ 5 3 
1 0. 1. 7. 1  
P har mac o ki netic a n al ysis set  .................................................. 5 3 
1 0. 1. 8  
Usa ge of t he a nal ysis sets  ................................................................. 5 3 
1 0. 2  
Varia bles  ....................................................................................................... 5 4 
1 0. 2. 1  
Pri mar y efficac y v aria ble(s)  .............................................................. 5 4 
1 0. 2. 2  
Ke y sec o n d ar y efficac y v aria bles  ..................................................... 5 4 
1 0. 2. 3  
P har mac o ki netic a n d p h ar mac o d y na mic v aria bles  ........................... 5 4 
1 0. 2. 3. 1  
P har mac o ki netic varia bles  ...................................................... 5 4 
1 0. 2. 3. 2  
P har mac o d y na mic v aria ble s ................................................... 5 5 
1 0. 2. 4  
Safet y v aria bl es  ................................................................................. 5 5 
1 0. 2. 4. 1  
A d verse e ve nts  ....................................................................... 5 5 
1 0. 2. 4. 2  
A d verse e ve nt of s pecific i nterest: He m orr h a ge  .................... 5 5 
1 0. 2. 4. 3  
La b orat or y d ata  ....................................................................... 5 5 
1 0. 2. 4. 4  
Vital si g ns  ............................................................................... 5 6 
1 0. 3  
Descri pti o n of statistical a nal ys e s ................................................................. 5 6 
1 0. 3. 1  
O verall testi n g strate g y  ..................................................................... 5 6 
1 0. 3. 2  
A nal ysis of effi cac y v ari a ble(s)  ........................................................ 5 6 
1 0. 3. 3  
A nal ysis of t h e p har mac o d y na mic v aria bles  .................................... 5 6 
1 0. 3. 3. 1  
H y p ot hes es a n d statistical m o del  ........................................... 5 6 
1 0. 3. 3. 2  
Ha n dli n g of missi n g data  ........................................................ 5 7 
1 0. 3. 3. 3  
Mai n a nal ysis  .......................................................................... 5 7 
1 0. 3. 3. 4  
S u p p orti ve/se nsiti vit y a n al yses .............................................. 5 8  
1 0. 3. 4  
A nal ysis of t h e p har mac o ki netic varia bles ....................................... 5 8  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 9 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
1 0. 3. 5  
A nal ysis of t h e safet y v aria ble(s)  ...................................................... 5 8 
1 0. 3. 5. 1  
A d verse e ve nts  ....................................................................... 5 8 
1 0. 3. 5. 2  
La b orat or y d ata  ....................................................................... 5 9 
1 0. 3. 5. 3  
Vital si g ns a n d w ei g ht  ............................................................ 5 9 
1 0. 3. 5. 4  
Safet y m o nit ori n g of maj or blee di n g a n d deat h ..................... 5 9  
1 0. 4  
I nteri m a nal yses ............................................................................................ 5 9 
1 0. 5  
Sa m ple size  ................................................................................................... 5 9 
1 1  D A T A H A N D LI N G  .................................................................................................... 6 0 
1 1. 1  
Data c ollecti o n  .............................................................................................. 6 0 
1 1. 2  
Mai nte na nce of data c o nfi de ntialit y  ............................................................. 6 0 
1 1. 3  
Data base m a na ge m e nt a n d q ualit y c o ntr ol  ................................................... 6 1 
1 2  P R O C E D U R E S A N D G O O D C LI NI C A L P R A C TI C E  ............................................. 6 2 
1 2. 1  
Et hics a n d G o o d Cli nical Practice  ................................................................ 6 2 
1 2. 2  
I n d e pe n de nt Et hics C o m mittee / I nstit uti o nal Re vie w B oar d ...................... 6 2 
1 2. 3  
I nf or me d c o ns e nt .......................................................................................... 6 2 
1 2. 4  
C o m pe nsati o n t o s u bjects a n d i n vesti gat ors ................................................. 6 3  
1 2. 5  
Pr ot oc ol a d here n ce/c o m plia nce  .................................................................... 6 4 
1 2. 6  
Pr ot oc ol a me n d me nts ................................................................................... 6 4  
1 2. 7  
Esse ntial d oc u me nts a n d rete nti o n of d oc u me nts ......................................... 6 4  
1 2. 8  
M o nit ori n g .................................................................................................... 6 5  
1 2. 9  
I n v esti gat or Site File ..................................................................................... 6 6 
1 2. 1 0  
A u dit ............................................................................................................. 6 7  
1 2. 1 1  
I ns p ecti o ns .................................................................................................... 6 7 
1 2. 1 2  
Re p orti n g of st u d y res ults a n d p u blicati o n ................................................... 6 7  
1 3  R E F E R E N C E S  ............................................................................................................ 6 9 
1 4  A P P E N DI C E S  ............................................................................................................. 7 3 
 
 
 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 1 0 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
 
LI S T O F T A B L E S 
 
Ta ble 1  
Pre parati o n of st u d y treat me nt f or s.c. a d mi nistrati o n .............................. 3 7  
Ta ble 2  
Visit a n d assess me nt sc h e d ule ................................................................... 4 1  
Ta ble 3  
Usa ge of a nal ysis datasets  ......................................................................... 5 4 
Ta ble 4  
Ass u m pti o ns f or t he res p o nse rate u n d er t he n ull a n d alter nati ve 
h y p ot hes es a n d sa m ple si ze ....................................................................... 6 0  
LI S T O F FI G U R E S 
 
Fi g ure 1  
St u d y d esi g n  .............................................................................................. 3 0 
 
LI S T O F A P P E N DI C E S 
 
A p pe n di x 1  
TI MI ris k sc or e .......................................................................................... 7 3  
A p pe n di x 2  
Killi p class f or MIs  .................................................................................... 7 4 
 
 
 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 1 1 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
LI S T O F A B B R E VI A TI O N S A N D A C R O N Y M S 
A C S   
Ac ute c or o n ar y s y n dr o m e  
A D P   
A de n osi ne di p h os p hate  
A E   
A d verse e ve nt  
A E SI   
A d verse e ve nt of s pecific i nterest  
A MI   
Ac ute m y ocar dial i nfarcti o n  
C A D   
C or o nar y art er y diseas e  
C F R   
C o de of Fe d eral Re g ul ati o ns ( U S)  
CI   
C o nfi de nce i nter v al  
C ma x   
Ma xi m u m plas ma c o nce ntrati o n  
C R A   
Cli nical Researc h Ass o ciate  
C R O   
C o ntract Researc h Or ga nizati o n  
C S R   
Cli nical st u d y re p ort  
C V   
C oefficie nt of v ariati o n  
C Y P   
C yt o c hr o me P 4 5 0  
E C G   
Electr ocar di o gra m  
e C R F  
Electr o nic case re p ort f or m  
e G F R   
Esti mate d gl o mer ular filtrati o n rate  
E O S   
E n d -of -St u d y  
E S C   
E ur o pea n S ociet y of C ar di ol o g y  
F A S   
F ull a nal ysis set  
G C P   
G o o d Cli nical Practice  
i. v.  
I ntr a ve n o us 
I B  
I n v esti gat or’s Br oc h ure 
I C F  
I nf or me d c o ns e nt f or m 
I C H  
I nter nati o nal C o u ncil f or Har m o nisati o n 
I E C  
I n d e pe n de nt Et hics C o m mittee 
I P A  
I n hi biti o n of platelet a g gre gati o n 
I R B  
I nstit uti o nal Re vie w B oar d 
I S E C  
I n d e pe n de nt Safet y E ve nt C o m mittee 
I S F  
I n v esti gat or Site File 
L T A   
Li g ht tra ns missi o n a g gre g o metr y  
Me d D R A   
Me dical Dicti o nar y f or R e g ul at or y Acti vities  
m F A S   
M o difie d F ull a nal ysis set  
MI   
M y ocar dial i nfarcti o n  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 1 2 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
M R P 2   
M ulti dr u g resista nce pr ot ei n 2  
M T D   
Ma xi m u m t olerate d d ose  
N S T E MI   
N o n -S T -se g me nt ele v ati o n m y ocar dial i nfarcti o n 
O A T P   
Or ga nic a ni o n -tra ns p orti n g p ol y pe pti de 
P -A M   
Acti ve meta b olite of pras u grel  
P CI   
Perc uta ne o us c or o nar y i nter ve nti o n  
P D   
P har mac o d y na mic(s)  
PI   
Pri nci pal I n v esti gat or  
P K   
P har mac o ki netic(s)  
P P S   
Per -pr ot oc ol a n al ysis set  
P R U   
P 2 Y 1 2 reacti o n u nits 
R SI   
Refere n ce s afet y i nf or m ati o n  
s.c.  
S u bc uta ne o us(l y)  
s.l.  
S u bli n g ual  
S A D   
Si n gle -as ce n di n g d ose  
S A E   
Seri o us a d verse  e ve nt  
S A F   
Safet y a nal ysis set  
S A P   
Statistical a nal ysis pla n  
S D   
Sta n dar d de viati o n  
S E   
Sta n dar d err or  
SI V   
Site i nitiati o n visit  
S T   
Ste nt t hr o m b osis  
S T E MI   
S T -se g m e nt ele vati o n m y o car dial i nfarcti o n 
S U S A R   
S us pecte d u ne x pecte d seri o us a d verse reacti o n 
t½   
Ter mi nal  half -life 
T E A E   
Treat me nt -e mer ge nt a d v erse e v e nt  
T E A E SI   
Treat me nt -e mer ge nt a d v erse e v e nts of s pecific i nterest  
TI MI   
T hr o m b ol ysis i n m y o car dial i nfarcti o n  
tma x   
Ti me t o reac h ma xi m u m plas ma c o nce ntrati o n  
 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 1 3 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
N O N -S U B S T A N TI A L G L O B A L  A M E N D M E N T 1  
 
A me n d me nt r ati o n ale 
T his a me n d me nt a p plies t o gl o bal pr ot oc ol I D- 0 7 6 A 2 0 2 Versi o n 1 date d 1 3 Marc h 2 0 1 8 . 
T he res ulti n g a me n de d gl o bal pr ot oc ol is Versi o n 2 date d 1 1 A pril 2 0 1 8. 
T he reas o n s f or t his a me n d me nt are t o pr o vi de t h e f oll o wi n g clarificati o n: 
•  T he  la b orat or y  ass ess me nt “Acti vate d  Cl otti n g  Ti me ” is  a  p oi nt- of-care  test  w hi c h 
ca n n ot  be  perf or m e d  ce ntrall y a n d  will  be  perf or me d at  eac h  site  l ocall y.  I n 
S ecti o n 7. 2. 5. 1, it was i n dicate d t hat all st u d y-s pecific assess me nts will be perf or me d 
ce ntrall y, t his s ecti o n is a me n de d t o clarif y t h at t h e “A cti vate d Cl otti n g Ti me ” will be 
perf or me d l o call y.  
C h a n ges t o t he pr ot oc ol  
T w o versi o ns of t h e a m e n de d pr ot oc ol will be pre pare d: 1) a cl ea n v ersi o n a n d 2) a W or d 
c o m paris o n  d oc u me nt,  s h o wi n g  d eleti o ns  a n d  i nserti o ns  i n  c o m paris o n  t o  t he  pre vi o us 
pr ot oc ol versi o n. 
A me n de d pr ot oc ol secti o ns 
T he  secti o ns  of  t he  pr ot oc ol  affecte d  b y  t his  a me n d me nt  are  liste d  bel o w.  W here 
a p plica ble, t he sa me c ha n ges ha ve als o b ee n m a de  t o t he  c orres p o n di n g  secti o ns of t he 
pr ot oc ol s y n o psis: 
7. 2. 5. 1  
T y pe of l a b or at or y 
7. 2. 5. 2  
L a b or at or y tests 
 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 1 4 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
P R O T O C O L S Y N O P SI S I D- 0 7 6 A 2 0 2 
TI T L E  
A  m ulti -ce nter,  o p e n -la bel,  ra n d o mize d  st u d y  t o  assess t he 
o nset  of  platelet  a g gre gati o n  i n hi biti o n  after  a  si n gl e 
s u bc uta ne o us  i njecti o n  of  A C T-2 4 6 4 7 5  i n  a d ults  wit h  ac ute 
m y ocar dial i nfarcti o n . 
O B J E C TI V E S  
Pri m ar y o bjecti ve  
T he pri mar y o bjecti ve of t he st u d y is t o assess t he i n hi biti o n of 
platelet 
a g gre gati o n  (I P A)  3 0  mi n utes  after  a  si n gle 
s u bc uta ne o us  (s.c.) i njecti o n  of  A C T-2 4 6 4 7 5  i n  s u bjects  wit h 
ac ute  m y ocar dial  i nfarcti o n  ( A MI ) recei vi n g  c o n ve nti o nal 
a ntit hr o m b otic treat me nt  (e. g.,  as piri n,  oral  P 2 Y1 2 rece pt or 
a nta g o nists, a ntic oa g ula nts). 
Ot h er o bjecti v es  
T he ot her o bjecti ves of t his st u d y are: 
•  T o  assess  t he p har m ac o ki netics  ( P K ) of  A C T -2 4 6 4 7 5  i n 
s u bjects wit h A MI. 
•  T o i n vesti gate s afet y a n d t olera bilit y of A C T - 2 4 6 4 7 5. 
D E SI G N  
T his  is  a  pr os p ecti ve,  m ulti -ce nter,  o pe n -la bel,  ra n d o mize d, 
parallel -gr o u p,  P hase  2,  e x pl orat or y  st u d y  of  a  si n gle  s.c. 
a d mi nistrati o n of A C T -2 4 6 4 7 5, at t w o differe nt d ose le vels, i n 
s u bjects  wit h  A MI  (S T -se g me nt  el e vati o n MI   [S T E MI ]  or 
n o n- S T E MI  [N S T E MI] ) sc he d ule d f or i n v asi ve strate g y. 
A p pr o xi matel y  4 2  a d ult  s u bjects  wit h  c o nfir m e d  dia g n osis  of 
A MI ( S T E MI or N S T E MI) , a n d ti me fr o m o nset of s y m pt o ms 
of m ore t ha n 3 0 mi n a n d less t ha n 6 h o urs , will be ra n d o mize d 
t o recei ve A C T-2 4 6 4 7 5 at t he d ose of eit her 8 m g or 1 6  m g, i n 
a 1: 1 rati o, i njecte d s.c. i n t he t hi g h i n a d diti o n t o c o n ve nti o nal 
sta n dar d- of-care  treat me nt.  I njecti o n  of  A C T -2 4 6 4 7 5  will  be 
perf or me d as s o o n as p ossi ble after ra n d o mizati o n. 
T he st u d y c o m prises t he f oll o wi n g c o ns ec uti ve peri o ds: 
Scree ni n g  peri o d:  Starts w he n  t he  s u bject  gi ves i nf or me d 
c o nse nt (orall y  or i n writi n g as des cri be d i n Secti o n  1. 4. 3 ) a n d 
e n ds wit h s u bject’s ra n d o mizati o n. 
Tre at me nt  peri o d:  Starts  wit h  s u bject ’s  ra n d o mizati o n a n d 
e n ds after t he E n d -o f-St u d y  ( E O S) ass ess me nts,  a p pr o xi matel y 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 1 5 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
4 8 h after t he a d mi nistrati o n of a si n gle st u d y treat me nt d ose . 
P L A N N E D D U R A TI O N  
A p pr o xi matel y 4  m o nt hs  fr o m  first  s u bject,  first  visit  t o  last 
s u bject, last visit. 
SI T E S 
/ C O U N T RI E S  
A p pr o xi matel y 3 – 8  sites i n 1 – 2  c o u ntries are pl a n ne d.  
I N C L U SI O N C RI T E RI A 
1)  Inf or me d  c o nse nt  o btai ne d  pri or  t o  a n y  st u d y -ma n date d 
pr oce d ure. 
2)  Males 
a ge d  fr o m  1 8  t o  8 5  a n d  p ost me n o pa usal  fe males 
a ge d  u p  t o  8 5  years .  P ost me n o pa usal  is  defi ne d  as 
1 2 c o nsec uti ve  m o nt hs  wit h 
n o  me nses  wit h o ut  a n 
alter nati ve me dical ca us e . 
3)  O nset  of  s y m pt o ms  of A MI  of  m ore  t ha n  3 0  mi n  a n d  less 
t ha n 6 h o urs pri or t o ra n d o mizati o n. 
4)  S u bjects prese nti n g  a  t y p e  I  A MI  i n cl u di n g  S T E MI  or 
N S T E MI d efi ne d as f oll o w: 
a)  S T E MI:  ne w  pers iste nt  S T-se g m e nt  ele vati o n  ≥  1  m m 
( 1 m V) i n t w o or m ore c o nti g u o us E C G lea ds, or 
b)  N S T E MI:  E C G  c h a n ges  c o m pati ble  wit h  m y o car dial 
isc he mia  wit h o ut  persiste nt  S T-se g me nt  ele v ati o n  a n d 
ele vate d  tr o p o ni n  defi n e d  as  a  tr o p o ni n  T  or  I le vel 
≥ 1. 5 ×  t he u p per li mit of n or mal. 
5)  Esti mate d b o d y  w ei g ht ≥ 4 0 k g ( 88 l bs). 
E X C L U SI O N C RI T E RI A  
C o n diti o ns ass oci ate d wit h t he q u alif yi n g A MI:  
1)  Car di o ge nic s h oc k or s e vere he m o d y n a mic i nsta bilit y (e. g., 
Killi p class 3 – 4).  
2)  Car di o p ul m o nar y res uscitati o n.  
3)  L oa di n g d ose  of a n y oral P 2 Y 1 2 rece pt or a nt a g o nist pri or t o 
ra n d o mizati o n. 
Blee di n g ris ks:  
4)  Acti ve i nter n al blee di n g, or blee di n g diat h esis or c o n diti o ns 
ass ociate d  wit h  hi g h  ris k  of  blee di n g  (e. g.,  cl otti n g 
dist ur ba nces, gastr oi ntesti nal blee d, he m o pt ysis). 
5)  K n o w n cli nicall y i m p orta nt a ne mia.  
6)  Oral  a ntic o a g ulati o n  t hera p y  wit hi n  7  da ys  pri or  t o 
ra n d o mizati o n. 
7)  Pla n ne d  fi bri n ol ytic  t h era p y  or  a n y  fi bri n ol yti c  t hera p y 
a d mi nistere d wit hi n 2 4  h pri or t o ra n d o mizati o n.  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 1 6 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
8)  K n o w n  
platelet  
dis or ders  
(e. g.,  
t hr o m b oast he nia, 
t hr o m b oc yt o pe ni a, v o n Wille bra n d disease). 
C o n diti o ns t h at m a y eit her p ut t he s u bject at ris k or 
i nfl ue nce t he res ults of t he st u d y: 
9)  E n d -sta ge re nal fail ure re q uiri n g dial ysis. 
1 0)  A n y  cli nicall y  si g nifi ca nt  fi n di n gs  o n  a  p h ysical  e x a m,  or 
la b orat or y  tests  t hat  i n t he  i n vesti gat or’s  j u d g m e nt  w o ul d 
precl u de  safe  or  relia ble  partici pati o n  of  a  s u bject  i n  t he 
st u d y. 
1 1)  C o nc o mita nt diseases (e. g., a d v a nce d li ver cirr h osis, me ntal 
ill ness,  ne ur o de ge nerati ve  disease,  ter mi nal  mali g na n c y …) 
or  c o n diti o ns  (e. g.,  i na bilit y  t o  c o m m u nicate  well  wit h t he 
i n vesti gat or i n t h e l ocal l a n g u a ge) t hat, i n t he o pi ni o n of t he 
i n vesti gat or, m a y p ut t he s u bject at ris k, pre ve nt t he s u bject 
fr o m  c o m pl yi n g  wit h  st u d y  re q uire m e nts  or  ma y  be  a 
c o nf o u n der f or t he st u d y i nter pretati o n. 
1 2)  Cli nicall y  re le v a nt  s ki n  disease  t hat  pre ve nts  s.c.  i njecti o n 
i n t he t hi g h, acc or di n g t o t he i n vesti gat or’s j u d g m e nt. 
1 3)  K n o w n  use  of  i n hi bit ors  of  O A T P 1 B 1  or  O A T P 1 B 3  (e. g., 
rit o na vir,  clarit hr o m yci n,  er yt hr o m yci n,  c ycl os p ori ne, 
ge mfi br ozil) at scree ni n g.  
1 4)  K n o w n  h y perse nsi ti vit y  t o  A C T-2 4 6 4 7 5,  a n y  of  its 
e x ci pie nts, or dr u gs of t h e P 2 Y 1 2 class. 
1 5)  Pre vi o us  e x p os ure  t o  a n  i n vesti gati o nal  dr u g  wit hi n 
3  m o nt hs pri or t o scree ni n g.  
S T U D Y T R E A T M E N T S  
I n vesti g ati o n al tre at me nt 
St u d y  treat me nt  f or  s. c.  a d mi nistrati o n  will  be  a vaila ble  as 
seale d glass vials i n 1 stre n gt h: 2 0 m g. T h e vials c o ntai n 2 2 m g 
of  l y o p hilize d  
A C T -2 4 6 4 7 5 A  ( h y dr oc hl ori de  salt  
of 
A C T -2 4 6 4 7 5)  t o  be  rec o nstit ute d  wit h  1  m L  of  water  f or 
i njecti o n.  F urt her  dil uti o n  wit h  1  m L  Na Cl  0. 9 %  will  be 
perf or me d  f or  pre p arati o n of  t he  d ose  of  8  m g.  T he  s.c. 
f or m ulati o n c o ntai ns ma n nit ol as a n i nacti ve i n gre die nt. 
St u d y treat me nt will be gi ve n as a si n gl e d ose of A C T - 2 4 6 4 7 5 
( 8  or  1 6  m g)  i n  a  v ol u me  of  0. 8  m L,  a d mi nistere d  s.c.  i n  t he 
t hi g h at site b y q ualifie d pers o n nel (e. g., n urse, p h ysicia n). 
C O N C O MI T A N T 
T H E R A P Y  
All o w e d c o nc o mit a nt t h er a p y 
Sta n dar d treat me nt of A MI is all o we d i ncl u di n g a ntic oa g ula nts 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 1 7 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
a n d oral P 2 Y 1 2 rece pt or a nta g o nists. 
W he n  i nitiati o n  of  a n  oral  P 2 Y1 2 rece pt or  a nta g o nist  is 
c o nsi dere d  f or  a  s u bject,  it 
m ust 
be 
i nitiate d  after 
a d mi nistrati o n  of  A C T - 2 4 6 4 7 5. I n  a bse nce  of  cli nical  data 
re gar di n g  a d mi nistrati o n  of  a n  irre versi ble  P 2 Y1 2  a nta g o nist 
f oll o wi n g t he a d mi nistrati o n of A C T-2 4 6 4 7 5, it is re q ueste d t o 
use a re v ersi ble oral P 2 Y 1 2 rece pt or a nta g o nist (e. g., tica grel or). 
F or bi d de n c o nc o mit a nt t her a p y  
T he  f oll o wi n g  me di cati o ns  are  pr o hi bite d  fr o m  s cree ni n g  a n d 
u p t o t he last P K bl o o d c ollecti o n: 
•  Fi bri n ol ytic t hera p y (e. g., stre pt o ki nase, alte plas e …). 
•  O A T P 1 B 1  a n d  O A T P 1 B 3  i n hi bit ors  (e. g.,  ataza na vir, 
rit o na vir, 
l o pi na vir,  
si me pre vir,  
clarit hr o m yci n, 
er yt hr o m yci n,  
c ycl os p ori ne,  
eltr o m b o pa g,  
la pati ni b, 
ge mfi br ozil, rifa m pi n) . 
•  Gl yc o pr otei n II b/IIIa i n hi bit ors. 
•  O ral 
irre versi ble P 2 Y 1 2 a nta g o nists  (cl o pi d o grel  or 
pras u grel) . 
•  Ca n grel or . 
E N D P OI N T S  
Pri m ar y e n d p oi nt  
T he pri mar y  e n d p oi nt  is  t he  res p o nse t o  t he  treat me nt  defi ne d 
f or  eac h  s u bject  as  a P 2 Y 1 2 reacti o n  u nits val ue <  1 0 0  at  t h e 
3 0 mi n  p ost -d ose  ti me  p oi nt,  as  meas ure d  vi a  Verif y N o w ® . 
T his c orres p o n ds t o a n I PA i n d uce d b y A D P > 8 0 %.  
S af et y e n d p oi nts  
T he  safet y  e n d p oi nts  will  be  assesse d  u p  t o  E O S,  i.e.,  o ver 
4 8 h o urs p ost treat me nt a d mi nistrati o n : 
•  Treat me nt -e mer ge nt a d verse  e v e nts  ( A Es )1 a n d  seri o us 
a d verse e ve nts.  
•  A E of s pecifi c i nterest ( A E SI): He m orr h a ge . 
•  C ha n ge  i n  vital  si g ns  (s yst olic  a n d  diast olic  arterial  bl o o d 
press ure  a n d  p ulse  rate)  fr o m  baseli ne  t o  all  assesse d  ti me 
                                                 
1 A treat me nt -e mer g e nt A E is a n y A E te m p orall y ass o ciate d wit h t he a d mi nistrati o n  of st u d y treat me nt ( u ntil 4 8 h o urs 
after st u d y treat me nt a d mi nistrati o n ) w h et h er or n ot c o nsi d ere d b y t h e i n vesti gat or as relate d t o st u d y tre at me nt. 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 1 8 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
p oi nts d uri n g t he st u d y.  
•  C ha n ge fr o m bas eli ne f or cli nical la b orat or y tests.  
•  Treat me nt -e mer ge nt mar ke d la b orat or y a b n or malities.  
P h ar m a c o ki netic e n d p oi nts  
P K  e n dp oi nts  i ncl u de  m a xi m u m  plas ma  c o nce ntrati o n   ( Cma x ) 
a n d ti me t o reac h C ma x  (tma x ). 
A S S E S S M E N T S  
Refer t o t he sc h e d ule of assess me nts i n  Ta ble 2 . 
S T A TI S TI C A L 
M E T H O D O L O G Y  
A n al ysis sets  
T he Scree ne d  a nal ysis  set  i ncl u des  all  s u bj ects  w h o  are 
scree n e d a n d h a ve a s u bj ect i de ntificati o n n u m ber. 
T he Ra n d o mize d  a nal ysis  set  i ncl u des  all  s u bjects  w h o  ha ve 
bee n assi g ne d t o a st u d y treat me nt.  
T he F ull  a nal ysis  set  ( F A S)  i ncl u des  all  ra n d o mize d  s u bjects 
w h o ha ve bee n a d mi nistere d t he st u d y treat me nt.  
T he m o difie d F A S  ( m F A S) i ncl u des all s u bjects fr o m t he F A S 
w h o ha ve a n assess m e nt of t he pri mar y e n d p oi nt.  
T he  Per -pr ot oc ol  set  i ncl u des  all  s u bjects fr o m  F A S w h o 
c o m plie d  wit h  pr ot oc ol  s ufficie ntl y  t o  all o w  a de q u ate 
esti mati o n  of  t he  treat me nt  effects  (criteri a  f or  s ufficie nt 
c o m plia nce will be detail e d i n t he statistical a nal ysis  pla n).  
T he  Safet y  a nal ysis set ( S A F) i ncl u des  all  s u bjects  w h o 
recei v e d at least o ne d ose of st u d y treat me nt.  
T he P K a nal ysis set  i ncl u des all s u bjects  i n t he SA F  w h o h a ve 
at  least o ne P K  sa m ple  c ollecte d  after  a d mi nistrati o n  of  st u d y 
treat me nt.  
M ai n  a n al ysis  
T he  pri mar y  a n al ysis  will  be  c o n d ucte d  usi n g  t h e  m F A S  a n d 
will c o nsi der t he treat me nt act uall y recei ve d ( w hic h ma y differ 
fr o m t he assi g ne d o ne). 
T he  a n al ysis  of  t he  pri mar y  e n d p oi nt  will  be  perf or me d f or 
eac h of t he t w o treat me nt d oses i n de pe n de ntl y, i.e., c o nsi deri n g 
2  n ull h y p ot heses (pr o p orti o n of p atie nts ac hie vi n g a res p o ns e 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 1 9 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
is less or e q ual t o 5 0 % ) at 0. 0 2 5 t y pe I err or eac h.  
T he st u d y will be declare d p ositi ve wit h re gar d t o t he pri mar y 
o bjecti ve,  if  at  least  1  of  t he  2  n ull  h y p ot h eses is rejecte d at 
0. 0 2 5 t y pe I err or le vel. 
S u bjects wit h o ut pri mar y e n d p oi nt assess me nt will be re place d.  
A  o ne -si de d  z-test  will  be  c o m p ute d  a n d  t he  9 5 % c o nfi de nce 
i nter val of t he pr o p orti o n of res p o n ders will be pr o vi de d.  
S u m mar y  of  res p o nse,  i n  ter ms  of  n u m ber  ( %)  of  res p o n di n g 
s u bjects, will be pr o vi de d. 
S a m ple size  
T he  sa m ple  size  is  bas e d  o n  t h e  st u d y  pri mar y  o bjecti ve  of 
assessi n g  I P A  3 0  mi n  after  A C T -2 4 6 4 7 5  a d mi nistrati o n,  as 
assesse d  b y  t h e  pr o p orti o n  of  s u bjects  ac hie vi n g  a  res p o nse 
(i.e., P 2 Y 1 2 reacti o n  u nits  [P R U ] <  1 0 0  at  3 0  mi n  p ost  st u d y 
dr u g a d mi nistrati o n).  T h e  sa m ple  size  s h o ul d  be  s ufficie nt  t o 
all o w t he rejecti o n at least o ne of t he n ull h y p ot hes es. 
T he st u d y s h o ul d i ncl u d e 2 1 s u bjects e val ua bl e f or t he pri mar y 
p har mac o d y n a mic  e n d p oi nt i n eac h ar m c o nsi d eri n g: 
•  a n  o verall  t w o -si de d  t y pe  I  err or  of  0. 0 5,  a dj uste d  f or 
m ulti plicit y  usi n g  t he  B o nferr o ni  met h o d  f or  eac h  of  t he 
2 n ull  h y p ot heses  (t esti n g  eac h  d os e  at  a n  al p h a  le vel  of 
0. 0 2 5), 
•  a p o wer of 9 0 %, a n d 
•  t he  f oll o wi n g  ass u m pti o ns  f or  t he  res p o ns e  rate  u n der  t h e 
n ull  a n d  alter nati ve  h y p ot heses  as  re p orte d  i n  t he  ta ble 
bel o w. 
 
P r o p orti o n of 
res p o n ders 
u n der H 0 
P r o p orti o n of 
res p o n ders 
u n der H 1 
N u m ber of 
s u bjects 
(t ot al) 
N u m ber of 
s u bjects 
( per ar m) 
5 0 % 
8 5 %  
4 2 
2 1 
 
 
 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 2 0 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
S T U D Y C O M MI T T E E S  
T he I n de pe n d e nt  Safet y  E ve nt  C o m mittee  (I S E C) i n v ol ve d  i n 
t he  I D-0 7 6 A 2 0 1  st u d y  will  als o  re vie w  safet y  data  fr o m  t his 
st u d y. It c o nsists of t w o  i n de pe n de nt cli nical e x perts w h o will 
re vie w  safet y  data  i n d e p e n de ntl y  fr o m  t he  s p o ns or  d uri n g  t h e 
stu d y. T he I S E C has o v erall res p o nsi bilit y f or s afe g u ar di n g t he 
i nterests  of  s u bjects  b y  m o nit ori n g  safet y  data  o btai ne d  i n  t he 
st u d y  a n d  ma ki n g  a p pr o priate  rec o m me n dati o ns  base d  o n  t he 
re p orte d  data.  T h e I S E C will  be  f ull y  o perati o nal  pri or  t o 
e nr oll me nt of t he first s u bject i nt o t he st u d y. 
T he  I S E C will  s pecificall y  f oc us  o n  st u d y -dr u g -r elate d 
cli nicall y  rele va nt  maj or  blee di n g  e ve nts,  acc or di n g  t o  t he 
t hr o m b ol ysis i n m y ocar dial i nfarcti o n ( TI MI) defi niti o n . 
 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 2 1 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
P R O T O C O L 
1  
B A C K G R O U N D 
1. 1  Pre- h os pit al tre at me nt of a c ute m y oc ar di al i nf arcti o n  
Des pite  mar ke d  i m pr o ve me nt  of  i n -h os pital  ma na ge me nt  of  patie nts  wit h  ac ute 
m y ocar dial  i nf arcti o n  ( A MI)  i n  t he  past  d eca d es,  t here  is  still  a  me di cal  nee d  f or  a n 
earlier treat me nt o pti o n t o re d u ce hi g h platelet reacti vit y o n ce a s ec o n d ar y e ve nt occ urs 
[Na bel  2 0 1 2]. I n  patie nts  wit h  s us pecte d  ac ut e  c or o nar y  s y n dr o me ( A C S),  the  me dia n 
ti me t o me dical i nter ve nti o n i n ec o n o micall y a d va nce d c o u ntries, eit her i n a n a m b ula nce 
or at t he e mer ge nc y de part me nt, is still bet wee n 2 a n d 4 h after o nset of s y m pt o ms , wit h 
patie nt decisi o n ti me c o ntri b uti n g si g nifica ntl y t o t he pre -h os pital dela y  i n  see ki n g  care 
[Gar ofal o  2 0 1 2, T u bar o 2 0 1 1]. 
Patie nts  e x perie nci n g  a n  A MI  h a ve  hi g hl y  reacti ve platelets,  w hic h  are  i ns ufficie ntl y 
i n hi bite d, e ve n w he n t he y ar e recei vi n g d u al a nti platelet t hera p y wit h acet ylsalic ylic aci d 
a n d cl o pi d o grel [G ur bel 2 0 0 3, Matetz k y  2 0 0 4, W a n g  2 0 1 0]. A rece nt o bser vati o nal st u d y 
s h o we d t hat t he maj orit y of patie nts pres e nti n g wit h S T -se g me nt ele v ati o n MI  (S T E MI ) 
d ue  t o  c or o nar y  ste nt  t hr o m b osis  a n d u n der g oi n g  pri mar y  p erc uta n e o us  c or o nar y 
i nter ve nti o n ( P CI),  ha d  hi g h  plat elet  reacti vit y  wh et her  t h e y  were  o n  mai nte na nce 
a nti platelet  t hera p y  w hil e  de vel o pi n g  ste nt  t hr o m b osis  or  l oa de d  wit h  P 2 Y 1 2 i n hi bit or 
(cl o pi d o grel, pras u grel or tica grel or) s h ortl y b ef ore i m me diate P CI [ G o dsc hal k 2 0 1 7]. 
T he earlier o ne i nter ve n es o n t he o n g oi n g platel et -ric h t hr o m b us res p o nsi ble f or A MI, t he 
hi g her  t he  c ha n ce  t o  a v oi d  earl y  deat h  a n d  irre versi ble  m y o car dial  da ma ge. T he 
ma xi m u m  p ote ntial  f or  m y ocar dial re perf usi o n  a n d  sal va ge  i n  patie nts  wit h S T E MI  is 
wit hi n  t he  first  1  t o 3 h o urs  after  s y m pt o m  o nset  (s o -calle d “g ol de n  ti me ”) 
[ Sa v o nitt o 2 0 1 7].  He nce,  s h orte ni n g  t he  ti me  t o  treat me nt  wit h  a n  a ntit hr o m b otic  a ge nt 
c o ul d  be  of  t hera p e utic  be nefit.  T he  E ur o pea n  S ociet y  of  Car di ol o g y  ( E S C)  g ui deli nes 
rec o m me n d  tica gr el or  a n d  pras u grel  as  a  first-li ne  a nti platelet  t hera p y  o n  t o p  of 
acet ylsalic ylic aci d i n A MI; h o w e ver, e vi de nce of t heir be nefit i n t he pre -h os pital setti n g 
is lac ki n g [Be y g ui 2 0 1 5, I b a nez 2 0 1 7]. 
A C T - 2 4 6 4 7 5,  a  s u bc uta ne o usl y (s.c.) a d mi nistere d   P 2 Y1 2 rece pt or  a nta g o nist  is  bei n g 
de vel o pe d f or self- i njecti o n i n patie nts wit h s us pecte d A MI. 
1. 2  St u d y tre at me nt  ( A C T- 2 4 6 4 7 5) 
A C T -2 4 6 4 7 5 is a ne w , p ote nt, re versi ble, a n d hi g hl y s electi ve P 2 Y1 2 rece pt or a nta g o nist 
wit h ra pi d o nset a n d a s h ort d urati o n of acti o n, s uita ble f or s.c. a d mi nistrati o n. Efficac y 
a n d  saf et y  st u dies  wit h  A C T -2 4 6 4 7 5  i n  a ni mal  t hr o m b osis  m o dels  s u g gest its  p ote ntial 
f or a n i m pr o ve d t hera p e utic wi n d o w i n cli nical use, as c o m pare d wit h c urre ntl y a vaila bl e 
oral a ge nts.  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 2 6 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
I n  t his  st u d y,  t he  hi g hest  d ose  pla n ne d  t o  be  use d  is  a  si n gle  d ose  of 1 6  m g,  w hic h  is 
t w o-f ol d  l o wer  t ha n  t he  hi g hest  d ose  a d mi nistere d  i n  t he A C - 0 7 6- 1 0 2  SA D  st u d y 
c o n d ucte d i n healt h y s u bjects. 
I n  st u dies A C - 0 7 6-1 0 1  a n d  A C - 0 7 6- 1 0 2, s.c.  ad mi nistrati o n  of A C T -2 4 6 4 7 5  has  bee n 
deter mi ne d  t o  b e  safe  a n d  well  t olerate d  at  differe nt  d os e  le v els ra n gi n g  fr o m  1 m g t o 
3 2 m g, a n d n o p artic ular safet y c o n cer n w as i de ntifie d.  
T his  st u d y  will  be  t he  first  A C T -2 4 6 4 7 5  st u d y  e nr olli n g  p atie nts  d uri n g  a n  ac ute MI 
e ve nt.  Acc or di n gl y,  t he  I n d e pe n d e nt Safet y  E v e nt C o m mittee  (I S E C) i n v ol ve d  i n  t he 
I D-0 7 6 A 2 0 1  st u d y (s u bj ects wit h sta ble C A D ) is  pla n ne d  t o re vie w  t he  data  fr o m  t his 
st u d y [ Secti o n 3. 3] . T his c o m mittee will ha v e o v erall res p o nsi bilit y f or safe g uar di n g t he 
i nterests  of  s u bjects  b y  m o nit ori n g  safet y  data ( wit h  s pecific  f oc us  o n  blee di n g  e v e nts) 
a n d ma ki n g a p pr o priate rec o m me n dati o ns b ase d o n t he re p orte d data, t h us e ns uri n g t hat 
t he st u d y is bei n g c o n d u cte d t o t he hi g hest sci e ntific a n d et hical sta n d ar ds. 
1. 4. 2  I nterf ere nce wit h or al P 2 Y 1 2 rece pt or a nt a g o nists 
C o- a d mi nistrati o n  of  t h e  or al,  irre versi ble  P 2 Y 1 2 rece pt or  a nta g o nists  cl o pi d o grel  a n d 
pras u grel  d uri n g  i nf usi o n  of  ca n grel or  is  pr o hi bite d  gi ve n t he p ote ntial  lac k  of 
cl o pi d o gr el- /  pras u gr el-me diate d I P A [Ke n gre x al ®  S m P C ].  Mec ha nisticall y,  t his  is  d u e 
t o t he s h ort h alf-life of t he acti ve meta b olites of cl o pi d o grel a n d pras u grel t hat, w hile still 
i n t he circ ulati o n, ca n n ot bi n d t o t he rece pt or w hic h is pre- occ u pie d b y ca n grel or. I nstea d, 
if  a d mi nistere d  i m me di atel y  aft er  st o p pi n g  t h e  ca n grel or  i nf usi o n,  cl o pi d o grel  a n d 
pras u grel  b ot h  e x hi bit  t heir  e x pecte d  P D  effects  [ Stei n h u bl 2 0 0 8, Sc h nei der  2 0 1 4, 
J u d ge 2 0 1 6, R olli ni  2 0 1 6]. 
I n vitr o st u dies  ha ve  bee n  c o n d u cte d  t o  ass ess  t he P D  i nteracti o n  p ote ntial  of 
A C T -2 4 6 4 7 5 wit h tica gr el or a n d t he acti ve meta b olite of pras u grel  ( P-A M ) [ B- 1 6. 0 6 4]. 
Here, a d diti ve  effects  were  deter mi ne d  w he n  A C T - 2 46 4 7 5  w as  a d d e d  t o  platelets 
pre -b o u n d t o tica grel or  or P -A M.  I nstea d, if P -A M was a d de d t o platelets pre -b o u n d t o 
A C T - 2 4 6 4 7 5 t he i n hi bit or y eff ects of P-A M o n pl atelet a g gre gati o n were re d uce d.  
Beca use  of  t he  c urr e nt  E S C  g ui deli nes [Val gi mi gli  2 0 1 8] rec o m me n di n g  a d mi nistrati o n 
of a l oa di n g d ose of oral P 2 Y 1 2 rece pt or a nta g o nist as earl y as p ossi ble after dia g n osis of 
a n A MI, it is e x pecte d t hat ma n y s u bjects p artici pati n g i n t he st u d y will recei ve a n oral 
P 2 Y 1 2 a nta g o nist.  
I n t he a bs e nce  of cli nical data  re gar di n g  a d mi nistrati o n  of t he irre versi ble  P 2 Y1 2 
a nta g o nist s  cl o pi d o gr el  or  pras u grel f oll o wi n g  a d mi nistrati o n of  A C T - 2 4 6 4 7 5, if  oral 
treat me nt  wit h  a  P 2 Y1 2 rece pt or  a nta g o nist  is t o  be  i nitiate d  i n s u bjects  partici pati n g  i n 
t his st u d y, a re v ersi ble P 2 Y1 2 rece pt or a nta g o nist (e. g., tica grel or) m ust be use d. 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 2 7 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
1. 4. 3  I ncl usi o n of v ul ner a ble s u bjects 
Eli gi ble  s u bjects  prese nt wit h  A MI ( S T E MI or  n o n- S T E MI  [ N S T E MI ]), w hic h  is  a 
life-t hreat e ni n g  c o n diti o n,  a n d t heref ore, f ulfill  I C H-G C P  defi niti o n  of  v ul nera ble 
s u bjects (“ pers o ns i n e mer ge nc y sit uati o ns”). 
T he mai n et hical ris k is t hat s u bject ’s writte n i nf or me d c o nse nt h as t o  be q uic kl y o btai ne d 
s o  t hat  t he  st u d y  treat me nt  ca n  b e  i nitiate d  as  s o o n  as  p ossi ble. I n  t his st u d y,  t he 
f oll o wi n g  pr ocess  will  b e  use d ( or  a n y  si milar  pr ocess  c o m plia nt  wit h  l o cal  re g ulati o n 
a n d t hat will be a p pr o ve d b y t he Et hics C o m mittee) : 
•  Recr uit me nt a n d ra n d o mizati o n , i n h os pital setti n gs, ca n b e perf or m e d b y e mer ge nc y 
me dical ser vices  pers o n n el (acc or di n g t o l ocal re g ulati o ns). 
•  Pre li mi nar y c o ns e nt ma y  be first o btai ne d ver ball y f oll o we d b y a si g ne d o ne as s o o n 
as p ossi ble ( de pe n di n g o n s u bject’s me dical c o n diti o n). 
•  All  eff orts  will  be ma de  t o  o btai n  t he  si g ne d  v ersi o n  of  t he  i nf or me d  c o nse nt f or m 
(I C F) pri or t o st u d y tr eat me nt a d mi nistrati o n.  
•  If s u bject’s c o n diti o n d oes n ot all o w o btai ni n g a si g ne d  I C F pri or t o st u d y treat me nt 
a d mi nistrati o n, s u bject’s c o nse nt will be o btai ne d orall y i n t h e pres e nce of a n i m partial 
wit ness . T he i m partial wit ness will si g n t he I C F b ef ore a n y st u d y-s pecific pr oce d ure is 
perf or me d a n d t h e s u bject ’s si g n at ure of t he I C F will be o btai ne d as s o o n as p ossi ble 
a n d n o later t ha n at ti me of disc har ge.  
T he me dical pers o n nel o btai ni n g t he preli mi nar y c o nse nt, will:  
•  E ns ure eac h patie nt is gi ve n f ull a n d a d e q uate o ral a n d writte n i nf or mati o n a b o ut t h e 
nat ure, p ur p os e, p ossi ble ris k a n d be nefit of t h e st u d y, 
•  E ns ure eac h p atie nt is n otifie d t hat t he y are free t o disc o nti n ue fr o m t he st u d y at a n y 
ti me, 
•  E ns ure t hat eac h patie nt is gi ve n t he o p p ort u nit y t o as k q uesti o ns. 
1. 4. 4  P ot e nti al ris ks ass oci ate d wit h st u d y -s pecific pr oce d ures 
T he r is ks ass ociate d wit h t he st u d y-s pecific pr o ce d ures are restrict e d t o t he sta n dar d ris ks 
ass ociate d wit h a n y bl o o d c ollecti o n. S uc h pr oce d ures are r o uti ne practice i n t he selecte d 
sites, a n d t heref ore , t he ris ks are c o nsi dered mi ni mal f or t he s u bjects . 
L at est E S C g ui deli nes [Val gi mi gli  2 0 1 8] rec o m me n d a d mi nistrati o n of a P 2 Y 1 2 recept or 
a nta g o nist as cl ose as p ossi ble t o dia g n osis  of A MI . All st u d y s u bj ects will recei ve acti ve 
st u d y dr u g ( A C T- 2 4 6 4 7 5) s o  t hat  n o ne  of  t he  s u bjects are  d e pri ve d of a  p ote ntiall y 
be neficial dr u g.  
A C T -2 4 6 4 7 5  will  be  a d mi nist ere d  o n  t o p  of  sta n dar d  of  care. Its P D  pr ofile  wit h  fast 
o nset of platelet i n hi biti o n, relate d t o its a d mi nistrati o n via s.c. r o ute, will all o w bri d gi n g 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 2 9 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
2. 2  Ot her o bje cti ves 
T he ot her o bjecti ves of t his st u d y are: 
•  T o assess t he P K of A C T - 2 4 6 4 7 5 i n s u bjects wit h A MI.  
•  T o i n vesti gate s afet y a n d t olera bilit y of A C T - 2 4 6 4 7 5. 
3  
O V E R A L L S T U D Y D E SI G N A N D P L A N 
3. 1  St u d y desi g n  
T his  is  a  pr os pecti ve, m ulti -ce nter, o pe n- l a bel,  ra n d o mize d,  parallel-gr o u p,  P hase  2, 
e x pl orat or y  st u d y of  a  si n gle  s.c.  a d mi nistrati o n  of  A C T -2 4 6 4 7 5,  at  t w o  differe nt  d ose 
le vels, i n s u bjects wit h A MI  ( S T E MI or N S T E MI) sc he d ule d f or i n vasi ve strate g y. 
A p pr o xi matel y 4 2 a d ult s u bjects wit h c o nfir me d dia g n osis of A MI ( S T E MI or N S T E MI ) 
a n d  ti me  fr o m  o nset  of  s y m pt o m s of  m ore  t ha n  3 0  mi n  a n d  less  t ha n  6  h o urs will be 
ra n d o mize d t o  recei ve  A C T- 2 4 6 4 7 5 eit her  at  t he  d ose  of 8 m g  or  1 6  m g , i n  a  1: 1  rati o 
i njecte d  s.c. i nt o t he  t hi g h i n  a dditi o n  t o  c o n ve nti o nal  sta n dar d -of -care  treat me nt . 
I njecti o n of A C T - 2 4 6 4 7 5 will be per f or me d as s o o n as p ossi ble after ra n d o mizati o n. 
S u bjects  ra n d o mize d  w h o ha ve  n ot  recei ve d  A C T - 2 4 6 4 7 5 or  w h o  d o  n ot  perf or m  t he 
3 0- mi n ute ti me p oi nt Verif y N o w ®  assess me nt will be re place d.  
T he st u d y will be c o n d ucte d at a p pr o xi matel y 3 – 8 sites i n 2 – 3 c o u ntries ( pla n ne d). 
3. 1. 1  St u d y peri o ds  
T he st u d y is c o n d ucte d d uri n g t he h os pitalizati o n of t he s u bject f or A MI a n d t he s u bjects 
will  re mai n h os pitalize d  d uri n g  t he  e ntire  st u d y  d urati o n.  T he  st u d y c o m prises   t he 
f oll o wi n g c o ns ec uti ve peri o ds: 
Scree ni n g p eri o d: Starts w he n t he s u bject gi ves i nf or me d c o nse nt ( orall y or i n writi n g, 
as descri be d i n S ecti o n 1. 4. 3) a n d e n ds wit h s u bject’s ra n d o mizati o n. 
Tre at me nt p eri o d: Starts wit h s u bject’s ra n d o mizati o n a n d e n ds after t he E n d - of-St u d y 
( E O S)  ass ess me nts, a p pr o xi matel y  4 8  h after t he  a d mi nistrati o n  of a  si n gl e st u d y 
treat me nt d ose.  
T he visit sc he d ule a n d pr ot oc ol -ma n date d pr oce d ures will be perf or me d acc or di n g t o t h e 
ta ble of assess me nts [Ta ble 2]  a n d are des cri be d i n S ecti o n 7.  
T he o ver all st u d y desi g n is de picte d i n  Fi g ure 1.  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 3 0 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
Fi g ure 1 
St u d y desi g n  
 
E O S: E n d -of -St u d y; P D: p h ar mac o d y n a mic; P K: p h ar mac o ki n etic ; S o C: sta n d ar d of care; X:  a d mi nistrati o n of A C T-
2 4 6 4 7 5 ( h 0) . 
 
3. 1. 2  St u d y d ur ati o n  
T he st u d y starts wit h t he first act of recr uit me nt (i.e., i nf or me d c o nse nt pr o vi de d b y  t h e 
first s u bject) a n d e n ds wit h t he c o m pleti o n of t he last s u bject ’s E O S assess me nts . 
T he  o verall  d urati o n of p artici pati o n i n t he st u d y  (i ncl u di n g scree ni n g peri o d) of a s u bject 
will be a p pr o xi matel y 2  da ys.  
3. 2  St u d y desi g n r ati o n al e 
T he d urati o n  of  t he tr eat me nt  peri o d  is  j ustifie d  b y  t he  pri mar y  o bjecti v e,  w hic h  is  t o 
c haracterize t he o ns et of I P A after a si n gle s.c. i nj ecti o n of A C T -2 4 6 4 7 5 at t w o differe nt 
d oses i n s u bjects wit h A MI. 
T he c h oice of t he sa m e t w o d oses (i.e., 8 a n d 1 6 m g) as i n t he o n g oi n g I D- 0 7 6 A 2 0 1 st u d y 
(see  Secti o n 5. 1. 1 f or  detaile d  rati o nale  o n  d ose  selecti o n),  will  pr o vi de  s u p p orti ve 
i nf or mati o n f or t he selecti o n of t he d ose t o be teste d i n t he P hase 3 pi v otal st u d y. 
T he I P A a nal ysis  will  be  p erf or m e d  wit h  t h e Verif y N o w ®  met h o d.  Res ults  fr o m 
Verif y N o w ®  are  well  c orrel ate d  wit h t h ose o btai ne d  wit h  t he li g ht  tra ns missi o n 
a g gre g o metr y  ( L T A ) met h o d 
[Vare n h orst 2 0 0 9,  Gre m mel  2 0 1 5].  T he Verif y N o w ®  
met h o d has bee n pr ef err e d as it is m ore  sta n d ar dize d t ha n t he L T A met h o d  a n d it is t he 
met h o d use d f or pri mar y P D a nal ysis i n t he o n g oi n g I D -0 7 6 A 2 0 1 st u d y i n s u bjects wit h 
sta ble  C A D. I n  a d diti o n,  t he  v ol u me  of  bl o o d  re q uire d  per  sa m ple  is  hi g her  f or  L T A 
( 6 m L)  t ha n  f or  t he V erif y N o w ®  met h o d  ( 3 m L) . Acc or di n gl y,  u si n g  t h e Verif y N o w ®  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 3 1 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
met h o d will re d uce t he a m o u nt of bl o o d c ollecte d f or st u d y p ur p os es i n a p o p ulati o n wit h 
ac ute isc he mic e ve nt.  
T he trial is c o n d ucte d  o pe n -la bel t o all o w t he i n vesti gat or  t o a da pt t he  sta n dar d  A MI 
treat me nts t o a n i n di vi d ual s u bject’s nee ds (e. g., a nti platelet a n d a ntic oa g ul a nt treat me nt). 
I n a d diti o n, t he pri mar y e n d p oi nt bei n g a p har mac ol o gical rea d o ut (P 2 Y 1 2 reacti o n u nits 
[P R U ] val ue  at  3 0  mi n)  wit h  n o  r o o m  f or  data  i nter pretati o n,  t he  o pe n -la bel  desi g n  is 
f ull y j ustifie d. Beca us e of t he li mite d sa m ple size a n d t he a bse nce of a place b o gr o u p , t h e 
prese ntati o n of t he s afet y data will be p urel y des cri pti ve.  
3. 3  St u d y c o m mittees 
T he I S E C i n v ol ve d i n t h e I D-0 7 6 A 2 0 1 st u d y will re vie w safet y data fr o m t his st u d y. It 
c o nsists of  t w o   i n de pe n de nt cli nical e x perts w h o will  re vie w  safet y  d ata  i n de pe n de ntl y 
fr o m t he s p o ns or d uri n g t he st u d y. T h e  I S E C has o verall res p o nsi bilit y f or safe g uar di n g 
t he  i nterests  of  s u bjects  b y  m o nit ori n g  s afet y  d ata  o btai ne d  i n  t he  st u d y  a n d  ma ki n g 
a p pr o priate  rec o m me n d ati o ns  base d  o n  t he  re p orte d  data.  T he I S E C will  be  f ull y 
o perati o nal pri or t o e nr oll me nt of t he first s u b ject i nt o t he st u d y. 
T he  I S E C will s pecificall y f oc us o n cli nicall y rel e va nt maj or blee di n g e v e nt s, acc or di n g 
t o t he t hr o m b ol ysis i n my o car dial i nfarcti o n ( TI MI) defi niti o n [ Me hra n 2 0 1 1]. 
T he  I S E C will be g o ver n e d b y a s pecific c hart er a n d r ec o m me n dati o ns ma de b y t he I S E C 
will be d oc u me nte d a n d arc hi ve d i n t he tri al master file. 
4  
S U B J E C T P O P U L A TI O N 
4. 1  S u bject p o p ul ati o n descri pti o n 
T his st u d y will e nr oll a d ult male s u bjects a ge d 1 8 t o 8 5 years  a n d p ost me n o pa usal fe mal e 
s u bjects a ge d u p t o 8 5 years , wit h c o nfir me d S T E MI or N S T E MI a n d o nset of s y m pt o ms  
fr o m 3 0 mi n t o 6 h o urs pri or t o ra n d o mizati o n. 
Eli gi ble s u bjects m ust b e a ble  a n d willi n g t o  gi v e i nf or me d  c o nse nt f or  partici pati o n i n 
t he cli nical st u d y. 
4. 2  R ati o n ale f or t he sele cti o n of t h e st u d y p o p ul ati o n 
I n t he ac ute p h ase of a n MI, a bs or pti o n of oral P 2 Y1 2 rece pt or a nta g o nists ca n be del a ye d 
[ Ale x o p o ul os 2 0 1 2, Par o di  2 0 1 3, M o ntalesc ot 2 0 1 4] . S u bject s e x perie nci n g a n A MI ma y 
als o  ha ve s y m pat hetic o ver -sti m ulati o n  a n d  c o nse q ue ntl y i m paire d  peri p heral  vasc ular 
circ ulati o n w hic h ma y  h a ve a n i m pact o n u pta k e of s.c. dr u gs [ B o nell o 2 0 1 5]. 
T he p o p ulati o n of t his st u d y is e x pecte d t o reflect t he ge neral p o p ulati o n of patie nts wit h 
A MI (S T E MI a n d N S T E MI ). It has bee n sel ecte d as it is cl ose t o t he tar get p o p ulati o n f or 
P hase  3  (s u bjects  w h o  will  self -i nject  A C T-2 4 6 4 7 5  w he n  t he y  e x perie nce  s y m pt o ms 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 3 2 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
s u g gesti ve  of  a n  A MI).  T he  res ults  fr o m  t his  st u d y t o get her  wit h  t he  o nes  fr o m  t he 
I D- 0 7 6 A 20 1 st u d y will s u p p ort t he selecti o n of t he A C T -2 4 6 4 7 5 d ose t o be use d i n t he 
P hase 3 st u d y. 
4. 3  I ncl usi o n criteri a 
F or i ncl usi o n i n t he st u d y, all of t he f oll o wi n g i ncl usi o n criteria m ust be f ulfille d. It is n ot 
per mitte d t o wai ve a n y of t he criteri a f or a n y s u bject:  
1)  I nf or me d c o ns e nt o btai ne d pri or t o a n y st u d y- m a n date d pr oce d ure. 
2)  Male s a ge d  fr o m  1 8  t o  8 5  years  a n d  p ost me n o pa usal  fe mal es  a ge d  u p  t o  8 5  years . 
P ost me n o pa usal  is  defi ne d  as  1 2  c o nsec uti ve  m o nt hs  wit h  n o  me nses  wit h o ut  a n 
alter nati ve me dical ca us e . 
3)  O nset  of  A MI  s y m pt o ms  of  m ore  t ha n  3 0  mi n a n d less  t ha n  6  h o urs pri or  t o 
ra n d o mizati o n. 
4)  Patie nts prese nti n g a t y p e I A MI i ncl u di n g S T E MI or N S T E MI defi ne d as f oll o w: 
a)  S T E MI: n e w  p ersiste nt  S T -se g m e nt  ele vati o n  ≥  1  m m  ( 1 m V)  i n  t w o  or  m ore 
c o nti g u o us E C G lea ds, or  
b)  N S T E MI:  E C G  c ha n ges c o m pati ble wit h m y ocar dial isc he mia wit h o ut persiste nt 
S T -se g m e nt  ele v ati o n  a n d ele vat e d  tr o p o ni n  defi ne d  as  a  tr o p o ni n  T  or  I l e vel 
≥ 1. 5 ×  t he u p per li mit of n or mal. 
5)  Esti mate d b o d y w ei g ht ≥ 4 0 k g ( 8 8 l bs.). 
4. 4  E x cl usi o n criteri a 
S u bjects  m ust  n ot f ulfill a n y  of  t he  f oll o wi n g  e x cl usi o n  criteria.  It  is  n ot  per mitte d  t o 
wai ve a n y of t h e criteria f or a n y s u bject:  
C o n diti o ns ass oci ate d wit h t he q u alif yi n g A MI : 
1)  Car di o ge nic s h oc k or s e v ere he m o d y n a mic i nsta bilit y (e. g., Killi p class 3 – 4).  
2)  Car di o p ul m o nar y res uscitati o n.  
3)  L oa di n g d os e of a n y oral P 2 Y 1 2 rece pt or a nta g o nist pri or t o ra n d o mizati o n. 
B lee di n g ris ks: 
4)  Acti ve i nter nal blee di n g,  or blee di n g diat hesis  or c o n diti o ns ass ociate d wit h hi g h ris k 
of blee di n g (e. g., cl otti n g dist ur ba nces, gastr oi ntesti nal blee d, he m o pt ysis). 
5)  K n o w n cli nicall y i m p orta nt a ne mia.  
6)  Oral a ntic oa g ul ati o n t her a p y  wit hi n 7 da ys pri or t o ra n d o mizati o n 
7)  Pla n ne d f i bri n ol ytic t her a p y or a n y fi bri n ol ytic t h era p y a d mi nistere d wit hi n 2 4  h pri or 
t o ra n d o mizati o n. 
8)  K n o w n  platelet  dis or ders  (e. g.,  t hr o m b oast he nia, t hr o m b oc yt o pe nia, v o n  Wille bra n d 
disease).  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 3 3 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
C o n diti o ns t h at m a y eit her p ut t he s u bject at ris k or i nfl ue nce t he res ults of t he 
st u d y: 
9)  E n d -sta ge r e nal fail ur e re q uiri n g dial ysis. 
1 0)  A n y cli nicall y si g nifica nt fi n di n gs o n a p h ysical e x a m, or la b orat or y tests t hat i n t he 
i n vesti gat or’s  j u d g me nt  w o ul d  precl u de  s afe  or  relia ble  partici pati o n  of  a  s u bject  i n 
t he st u d y. 
1 1)  C o nc o mita nt  
disease s 
(e. g.,  
a d v a nce d  
li ver  
cirr h osis,  
me ntal  
ill ness, 
ne ur o de ge n er ati ve  disease,  ter m i nal  mali g na n c y …)  or  c o n diti o ns (e. g.,  ina bilit y  t o 
c o m m u nicate well wit h t he i n vesti gat or i n t he l ocal la n g u a ge ) t hat, i n t he o pi ni o n of 
t he i n vesti gat or, ma y p ut t he s u bject at ris k, pre ve nt t he s u bject fr o m c o m pl yi n g wit h 
st u d y re q uire me nts or ma y be a c o nf o u n der f or t he st u d y i nter pretati o n. 
1 2)  Cli nicall y r ele va nt s ki n disease t hat pre ve nts s.c. i njecti o n  i n t he t hi g h, acc or di n g t o 
t he i n vesti gat or’s j u d g m e nt. 
1 3)  K n o w n u se of i n hi bit ors of O A T P 1 B 1 or O A T P 1 B 3 (e. g.,  rit o na vir, clarit hr o m yci n, 
er yt hr o m yci n, c ycl os p ori ne, ge mfi br ozil) at scree ni n g.  
1 4)  K n o w n h y pers e nsiti vit y t o A C T -2 4 6 4 7 5, a n y of its e x ci pie nts , or dr u gs of t he P 2 Y 1 2 
class. 
1 5)  Pre vi o us e x p os ure t o a n i n vesti gati o nal dr u g wit hi n 3 m o nt hs pri or t o scree ni n g. 
5  
T R E A T M E N T S 
5. 1  St u d y tre at me nt  
5. 1. 1  I n vesti g ati o n al tre at me nt ( A C T- 2 4 6 4 7 5): Descri pti o n a n d r ati o n ale 
St u d y  tr eat me nt  f or  s.c.  a d mi nistrati o n  will  be  a vaila ble  as  seale d  glass  vials  i n  o ne 
stre n gt h:  2 0  m g.  T h e  vi als  c o ntai n  2 2  m g  of  l y o p hilize d  A C T-2 4 6 4 7 5 A  ( h y dr oc hl ori de 
salt of A C T-2 4 6 4 7 5) t o be rec o nstit u te d wit h 1 m L of wat er f or i njecti o n  ( pre parati o n of 
st u d y  treat me nt  is  detail e d  i n  Secti o n 5. 1. 4) .  T he  s.c.  f or m ulati o n  c o ntai ns  ma n nit ol  as 
i nacti ve i n gre die nt. 
St u d y  tr eat me nt  will  be  gi ve n  as  a  si n gl e  d ose,  a d mi nistere d  s.c.  at  site  b y  q ualifie d 
pers o n nel (e. g., n urse, p h ysicia n). A C T - 2 4 6 4 7 5 will be a d mi nistere d i n t he t hi g h. 
A C T - 2 4 6 4 7 5 d oses of 8 m g or 1 6 m g  will be a d mi nistere d d uri n g t his st u d y. T hese d oses 
are i de ntical t o t h ose teste d i n s u bjects wit h sta ble C A D (S t u d y I D- 0 7 6 A 2 0 1). T he d oses 
of  A C T - 2 4 6 4 7 5 h a ve  bee n  selecte d  b ase d  o n  dat a  fr o m  t he  A C - 0 7 6- 1 0 2 S A D st u d y  to 
meet t he f oll o wi n g criteri a:  
•  T he  l o w  d ose  ( 8  m g)  is  t he  mi ni m u m d ose  ac hi e vi n g  at  least  8 5 %  I P A  f or  3  h o n 
a vera ge, c orres p o n d i n g t o a ti me peri o d d uri n g w hic h c o m plete s u p pressi o n of platelet 
reacti vit y  is  
n ee de d  
bef ore  s p ecific  i n-h os pital  
ma na ge m e nt  
of  
A C S  
[M o ntalesc ot  2 0 1 4]. 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 3 5 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
rec or di n g  t he  te m per at ur e.  A n y  te m perat ure  rec or di n g  s yste m  r o uti nel y  use d  at  t he  site 
will  be  acce pta bl e  as  l o n g  as  all  re q uire d  i nf or mati o n  is  i ncl u de d  a n d  certificati o n  of 
cali brati o n  is  pr o vi de d.  If  t he  te m perat ure  is  ca pt ure d  electr o nicall y,  a  pri nt o ut  will  be 
ma de a vaila ble t o t he Cli nical Researc h Ass ociat e (C R A ) d uri n g eac h o n-site visit.  
If a de vi ati o n fr o m t he a p pr o ve d te m perat ure ra n ge is i de ntifie d b y t h e st u d y ce nter, t h e 
de viati o n  m ust  be  re p orte d  t o  t he  C R A,  prefera bl y  i n  writi n g  a n d  wit h  s u p p orti n g 
d oc u me ntati o n  (e. g.,  c o p y  of  t he  te m perat ure  l o g  s h o wi n g  d ata  f or  all  e x c ursi o n  da ys). 
T he  C R A  will  i m me diatel y  c o ntact  t he  s p o ns or  f or  f urt her  a d vice.  T he  affecte d  st u d y 
treat me nt m ust n ot be use d (e. g., it will be se gre gate d p h ysi call y at t he st u d y ce nter) u ntil 
c o nfir m ati o n fr o m t he sp o ns or is o btai ne d t hat its use is safe. I f t he te m perat ure de viati o n 
is o utsi de of t he acce pta ble li mit, t he st u d y treat me nt will be k e pt se gre gate d at t he st u d y 
ce nter  a n d  r et ur ne d  t o  t he sp o ns or  f oll o wi n g  i nt er nal  st u d y  treat me nt  ret ur n pr ocesses. 
Ne w st u d y treat me nt s u p plies will be pr o vi de d t o t he st u d y ce nter.  
Te m perat ur e de viati o ns c orres p o n de n ce m ust be k e pt i n t he I n v esti gat or Site F ile (I S F). 
5. 1. 2. 3  St u dy tre at m e nt ret ur n a n d destr ucti o n  
O n a n o n g oi n g b asis a n d/ or o n ter mi nati o n of t he st u d y, t he C R A will c ollect use d a n d 
u n use d treat me nt kits, w hic h will be ret ur ne d t o t he ware h o us e. I n certai n circ u msta nces, 
use d  a n d  u n us e d  st u d y  treat me nt  c o nt ai ners  m a y  b e  d estr o ye d  at  t he  site  o nce  st u d y 
treat me nt  acc o u nt a bilit y  is  fi nalize d  a n d  has  bee n  verifie d  a n d  rec o ncile d  b y s p o ns or 
pers o n nel or t he d e p ut y, a n d writte n per missi o n  f or  destr ucti o n has b ee n  o btai ne d fr o m 
s p o ns or. F urt her details are pr o vi de d i n t he st u d y treat me nt ha n dli n g ma n ual. 
5. 1. 3  St u d y tre at me nt assi g n me nt a n d dis pe nsi n g  
5. 1. 3. 1  St u dy t re at m e nt assi g n me nt 
A fter  ha vi n g  verifie d  t hat  t he  s u bject  meets  all  i ncl usi o n  criteria  a n d  n o ne  of  t he 
e x cl usi o n criteria , t he s u bject will be ra n d o mize d  t o recei ve 8 or 1 6 m g of A C T - 2 4 6 4 7 5. 
T he  ra n d o mizati o n  list  will  be  ge nerate d  b y  a n  i n de pe n d e nt  C o ntr act  Researc h 
Or ga nizati o n ( C R O). 
T he  sites  will  be  pr o vi de d  wit h  seale d e n v el o pes  c o ntai ni n g  t he ra n d o mizati o n  n u m ber 
a n d c orr es p o n di n g treat me nt all ocati o n. At ra n d o mizati o n, f or eac h s u bject, o ne e n v el o pe 
will be o pe ne d, i n a se q u e ntial or der. 
5. 1. 3. 2  St u dy t re at m e nt dis pe nsi n g 
A treat me nt kit c o nsists of 1 vial of 2 0 m g A C T - 2 4 6 4 7 5. All treat me nt kits are i de ntical.  
After   r a n d o mizati o n,  t he site  will  ta ke  o ne  kit  p er  s u bject  a n d  pre pare  t he  st u d y  dr u g 
acc or di n g  t o  t he  ra n d o mizati o n  gr o u p  all ocate d  a n d  t he  i nstr ucti o ns  descri be d  i n 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 3 7 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
T a ble 1  
Pre p ar ati o n of st u d y tre at me nt f or s.c. a d mi nistr ati o n 
St u d y 
tre at me nt 
D ose  
V ol u me of 
w ater f or 
i njecti o n 
V ol u me of 
N a Cl 0. 9 %  
St oc k s ol uti o n 
c o nce ntr ati o n  
Ali q u ot of st oc k 
s ol uti o n t o be 
a d mi nistere d  
A C T -2 4 6 4 7 5  
8 m g  
1 m L  
1 m L  
1 0 m g/ m L  
0. 8 m L  
A C T -2 4 6 4 7 5  
1 6 m g  
1 m L  
N ot a p plica ble  
2 0 m g/ m L  
0. 8 m L  
 
5. 1. 5  Bli n di n g  
N ot a p plica ble. 
5. 1. 6  U n bli n di n g  
N ot a p plica ble. 
5. 1. 7  St u d y tre at me nt a cc o u nt a bilit y a n d c o m pli a nce wit h st u d y tre at me nt  
5. 1. 7. 1  St u dy tre at m e nt acc o u nt a bility  
T he 
i n ve nt or y  of  st u d y  tr eat me nt  dis pe nse d  a n d  ret ur ne d  (i. e.,  st u d y-treat me nt 
acc o u nta bilit y) m ust be p erf or me d b y site pers o n n el. It is t o be rec or de d b y site pers o n nel 
o n t he st u d y -treat me nt dis pe nsi n g a n d acc o u nt a bilit y l o g a n d i n t he electr o nic case re p or t 
f or m (eC R F ), v erifie d a n d rec o n cile d b y t h e C R A d uri n g t he r o uti ne site visits a n d at t he 
e n d of t he st u d y. T he st u d y treat me nt acc o u nta bilit y i n t he eC R F will i ncl u de at least t he 
f oll o wi n g  i nf or mati o n  f or  eac h  st u d y  treat me nt  u nit  (i.e.,  vial) a d mi nistere d t o  t he 
s u bject: 
•  Dis pe nse d vial n u m ber 
•  Date vial dis pe nse d  
All st u d y tr eat me nt s u p plies, i ncl u di n g partiall y use d or e m pt y vials, m ust be retai ne d at 
t he site f or re vi e w a n d r ec o nciliati o n b y t he C R A. 
5. 1. 7. 2  St u dy tre at m e nt c o m pli a nce 
St u d y  treat me nt  c o m plia nce  is  b ase d  o n a d mi nistrati o n  of  t he st u d y treat me nt  as 
all ocate d.  A n y  de viati o n  fr o m  ra n d o mizati o n  all ocati o n  will  be  re p orte d  as a pr ot oc ol 
de viati o n. 
5. 1. 8  St u d y tre at me nt d ose a dj ust me nts a n d i nterr u pti o ns  
St u d y treat me nt d ose a dj ust m e nts are n ot per mitte d . 
St u d y treat me nt i nterr u pti o ns are n ot a p plica bl e f or t his si n gle d ose st u d y. 
5. 1. 9  Pre m at ure disc o nti n u ati o n of st u d y tre at me nt  
N ot a p plica ble (si n gle- d ose st u d y). 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 3 8 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
5. 1. 1 0  St u d y -s pecific criteri a f or i nterr u pti o n / pre m at ure disc o nti n u ati o n of st u d y 
tre at me nt 
N ot a p plica ble (si n gle- d ose st u d y). 
5. 2  Pre vi o us a n d c o nc o mit a nt t her a p y 
5. 2. 1  Defi niti o ns  
A  pre vi o us  t hera p y  is  a n y  treat me nt  f or  w hi c h  t he  e n d  date  is  pri or  t o   gi vi n g i nf or me d 
c o nse nt. 
A  t hera p y  t hat  is  st u d y -c o nc o mita nt  is  a n y  treat me nt  t hat  is  o n g oi n g  or  i nitiate d  after 
pr o vi di n g i nf or me d c o ns e nt, or i nitiate d u p t o E O S . 
A t hera p y t h at is st u d y treat me nt -c o nc o mita nt is a n y treat me nt t hat is  eit her o n g oi n g at 
t he  start  of  st u d y  treat me nt  or  is  i nitiate d u p  t o  4 8  h o urs  after  st u d y  treat me nt 
a d mi nistrati o n . 
5. 2. 2  Re p orti n g of pre vi o us/c o nc o mit a nt t her a p y 
T he use of all st u d y -c o nc o mita nt t hera p y (i ncl u di n g tra diti o nal a n d alter nati ve me dici nes, 
e. g., pl a nt-, a ni mal-, or mi neral-bas e d me dici nes) will be rec or d e d i n t he eC R F.  
Pre vi o us  t hera pies  relate d  t o  trea t me nt  a n d  pre v e nti o n  of  C A D  will  be  rec or de d  i n  t he 
e C R F if disc o nti n ue d less t ha n 1 m o nt h ( ≤ 3 0 da ys) pri or t o pr o vi di n g i nf or me d c o nse nt. 
Pre vi o us t hera pies relat e d t o treat me nt of t he st u d y -q u alif yi n g A MI  will be rec or de d i n 
t he e C R F. 
T he ge neric na me, st art/e n d dates of a d mi nistrati o n (as well as w het her it was o n g oi n g at 
a d mi nistrati o n of st u d y treat me nt  a n d/ or  E O S),  r o ute,  d os e,  a n d  i n dicati o n  will  b e 
rec or d e d i n t he eC R F.  I n a d diti o n, f or oral P 2 Y1 2 rece pt or a nta g o nists, t he ti me of eac h 
a d mi nistrati o n d uri n g t he st u d y will be rec or de d i n t he e C R F.  
5. 2. 3  All o w e d c o nc o mit a nt t h er a p y  
Sta n dar d treat me nt of A MI is all o we d i ncl u di n g a ntic oa g ula nts a n d oral P 2 Y 1 2 rece pt or 
a nta g o nists. 
W he n  i nitiati o n of a n oral P 2 Y 1 2 rece pt or a nta g o nist is c o nsi dere d f or a s u bject [see als o 
S ecti o n 1. 4. 2] ,  it m ust be  i nitiate d  aft er  a d mi nistrati o n  of  A C T - 2 4 6 4 7 5. I n  a bse n ce of 
cli nical  data  re gar di n g  a d mi nistrati o n  of  a n  irre versi ble  P 2 Y 1 2 a nta g o nist  f oll o wi n g  t he 
a d mi nistrati o n  of  A C T -2 4 6 4 7 5,  it  is  re q ueste d  t o  use  a  re versi ble  oral  P 2 Y 1 2 rece pt or 
a nta g o nist (e. g., tica gr el or). 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 3 9 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
5. 2. 4  F or bi d de n c o nc o mit a nt t her a p y  
T he  f oll o wi n g  me dicati o ns  are  pr o hi bite d  fr o m  s cree ni n g  a n d  u p  t o t h e  l ast P K  bl o o d 
c ollecti o n: 
•  Fi bri n ol ytic t hera p y ( e. g., stre pt o ki nase, alte plas e …). 
•  O A T P 1 B 1 a n d O A T P 1 B 3 i n hi bit ors (e. g.,  ataza n a vir, rit o na vir, l o pi na vir, si me pre vir, 
clarit hr o m yci n,  er yt hr o m yci n,  c ycl os p ori ne,  eltr o m b o pa g,  l a pati ni b,  ge mfi br ozil, 
rifa m pi n) 
•  Gl yc o pr otei n II b/IIIa i n hi bit ors. 
•  Irre v ersi ble or al P 2 Y1 2 a nta g o nists (cl o pi d o grel or pras u grel) 
•  Ca n gr el or  
6  
S T U D Y E N D P O I N T S 
6. 1  Effic ac y e n d p oi nts 
N ot a p plica ble. 
6. 2  P h ar m ac o ki netic a n d p h ar m ac o d y n a mic e n d p oi nts  
6. 2. 1  P h ar m a c o d y n a mi c e n d p oi nts  
T he pri mar y P D e n d p oi nt is t he res p o nse t o t he treat me nt defi ne d f or  eac h  s u bject as a 
P R U val ue < 1 0 0 at t he 3 0 mi n  p ost-d ose ti me  p oi nt, as meas ure d via Verif y N o w® . T his 
c orres p o n ds  t o a n I P A i n d uce d b y  A D P >  8 0 % [Ga glia  2 0 1 1, Gre m mel  2 0 0 9, 
Vare n h orst  2 0 0 9]. 
A d diti o nal  P D  e n d p oi nts  relate d  t o  t he  m ai n  o nes  will  als o  be  c o nsi dere d  at  eac h  ti me 
p oi nt: 
•  P D pr ofile o ver ti me bas e d o n a bs ol ute P R U val ues at 1 5, 3 0 a n d 6 0 mi n p ost- d ose, 
•  P R U stat us ( val ue < 1 0 0) at t he 6 0 mi n p ost- d ose ti me p oi nt. 
6. 2. 2  P h ar m a c o ki netic e n d p oi nts  
•  Plas ma c o nce ntr ati o ns of A C T - 2 4 6 4 7 5 will be det er mi ne d at 1 5 mi n, 3 0 mi n , 1 h, a n d 
8 h p ost- d ose. 
•  C ma x . 
•  tma x . 
6. 3  S afet y e n d p oi nts 
T he saf et y  e n d p oi nts will be assesse d u p t o  e n d  of st u d y, i.e. , o ver 4 8 h  p ost treat me nt 
a d mi nistrati o n : 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 4 0 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
•  Treat me nt -e mer ge nt A Es 2 a n d S A Es . 
•  A E of s pecifi c i nterest ( A E SI): He m orr h a ge . 
•  C ha n ge  i n  vital  si g ns  (s yst olic  a n d  diast olic  arterial  bl o o d  press ure  a n d  p ulse  rate) 
fr o m baseli ne t o all assesse d ti me p oi nts d uri n g t he st u d y. 
•  C ha n ge fr o m bas eli ne t o f or cli nical la b orat or y tests.  
•  Treat me nt -e mer ge nt mar ke d la b orat or y a b n or malities.  
7  
VI SI T S C H E D U L E A N D S T U D Y A S S E S S M E N T S 
7. 1  St u d y visits 
T he  st u d y  is  perf or m e d  d uri n g a  s u bject ’s  h os pital  sta y  rel ate d  t o  t he  q ualif yi n g A MI. 
T his is c o nsi dere d t o be a si n gle visit, a n d assess m e nts  are liste d i n Ta ble 2.  
7. 1. 1  Scree ni n g/re -scree ni n g 
Scree ni n g starts w he n t h e s u bject has pr o vi de d i nf or me d c o ns e nt. T he d at e o n w hic h t h e 
first scree ni n g assess me nt is perf or me d c orres p o n ds t o t he date of t he st u d y vis it. 
It  is  t he  r es p o nsi bilit y  of  t he  i n vesti gat or/ dele gate  t o  o btai n  writte n  i nf or me d  c o nse nt 
fr o m eac h s u bject partici pati n g i n t his st u d y after a de q uate face-t o-face e x pla nati o n of t he 
o bjecti ves,  met h o ds,  a n d  p ote ntial  hazar ds  of  t he  st u d y.  T he  s u bjects w h o  will  be 
i ncl u de d  i n  t he  st u d y  ar e  c o nsi dere d  as  v ul nera ble a n d  a s pecific  c o nse nti n g  pr ocess  is 
detaile d i n S ecti o n 1. 4. 3.  
S u bjects  w h o  ha ve  pr o vi de d  i nf or me d  c o nse nt  will  be  all ocate d  a 7- di git s u bject 
i de ntificati o n  n u m ber w hic h  will  c o nsist  of : firsts 4 di gits  c orres p o n di n g  t o  t he  site 
i de ntificati o n  n u m ber  a n d  lasts 3 di gits  c orres p o n di n g  t o  t he  s e q ue ntial  or der  of 
recr uit me nt of t he s u bj ects fr o m t he site. 
S u bjects w h o ha v e pr o vi de d i nf or me d c o ns e nt w he n t he e nr oll me nt tar get has bee n met 
ma y still be ra n d o mize d.  
Re -scree ni n g is n ot per mitte d i n t his st u d y. 
7. 1. 2  U nsc he d ule d visits  
N ot a p plica ble as t he st u d y is c o n d u cte d o ver a si n gle visit. 
H o we v er, unsc he d ule d assess me nts  ma y be perf or me d at a n y ti me d uri n g t he st u d y base d 
o n t he j u d g m e nt of t he i n vesti gat or a n d t he res ults of t hese assess me nts will be rec or de d 
i n t he eC R F.  
                                                 
2 A treat me nt -e mer g e nt A E is a n y A E te m p orall y ass o ciate d wit h t he a d mi nistrati o n  of st u d y treat me nt ( u ntil 4 8 h o urs 
after st u d y treat me nt a d mi nistrati o n ) w h et h er or n ot c o nsi d ere d b y t h e i n vesti gat or as relate d t o st u d y tre at me nt. 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 4 1 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
T a ble 2 
Visit a n d assess me nt sc he d ule  
P E RI O D  
S C R E E NI N G  
T R E A T M E N T P E RI O D  
Visit  
Visit 1 
Ti me p oi nt  
Pre -d ose  
0 mi n  
1 5 mi n  
± 5 mi n  
3 0 mi n  
± 5 mi n  
6 0 mi n  
± 5 mi n  
8  h / P ost -
pr oce d ur e 1 
E O S  
4 8  h ± 2 h  
I nf or me d c o nse nt 
X 
 
 
 
 
 
 
Eli gi bilit y  
X 
 
 
 
 
 
 
De m o gra p hics a n d M e dical hist or y 
(i ncl u di n g TI MI ris k sc ore a n d Killi p class 
of MI)  
X 
 
 
 
 
 
 
P h ysical e xa mi n ati o n  
X 
 
 
 
 
 
 
B o d y wei g ht a n d h ei g ht (esti mate d)  
X 
 
 
 
 
 
 
Pre vi o us/c o n c o mita nt t h era p y  
X 
X 
X 
Vital si g ns ( B P a n d P R)  
X 
 
 
X  
X 
 
X 
P K b l o o d sa m pli n g 
 
 
X 
X  
X 
X 1 
 
V erif y N o w ®  
X 
 
X 
X  
X 
 
 
La b orat or y tests  
X 
 
 
 
 
 
X 
hs T n T  
X 
 
 
 
 
 
 
s.c. i njecti o n of A C T-2 4 6 4 7 5  
 
X 
 
 
 
 
 
A Es/ S A Es  
X 
X 
X 
( S) A E: (seri o us) a d verse e ve nt; B P: bl o o d press ure; E O S: E n d -of - St u d y; hs T n T: hi g h se nsiti vit y  tr o p o ni n T; MI: m y o car dial i nfarcti o n; P CI: perc uta ne o us 
c or o n ar y i n ter ve nti o n; P K: p h ar mac o ki n etic; P R: p ulse rate ; s.c.: s u b c uta n e o us; TI MI: t hr o m b ol ysis i n m y o car dial i nfarcti o n. 
1.  
T he 8  h P K p ost -d ose ti me p oi nt is fle xi ble.  If t h e s u bject gets a n i n vasi v e pr o ce d ure ( P CI/a n gi o gra p h y) wit hi n 8 h of st u d y dr u g a d mi nistrati o n, t he bl o o d 
sa m ple is t o b e c ollecte d at t h e e n d of t h e pr o ce d ure. If n o i n vasi ve pr o ce d ure is p erf or me d wit hi n 8  h of st u d y dr u g a d mi nistrati o n, t he bl o o d sa m ple is t o be 
c ollecte d a p pr o xi matel y 8  h after st u d y dr u g a d mi nistrati o n.  
 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 4 2 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
7. 2  St u d y assess me nts 
T he st u d y assess me nts  a n d t heir res pecti ve ti mi n g s are liste d i n Ta ble 2.  
All st u d y assess me nts will be perf or me d b y q ualifie d st u d y pers o n nel: me dical, n ursi n g, 
or  s pecialist  tec h nical  p ers o n nel,  a n d  will  be  rec or de d  i n  t he eC R F,  u nless  ot her wise 
s pecifie d. U nsc he d ule d assess me nts will  als o  be  rec or d e d  i n  t h e 
eC R F. 
It  is 
rec o m me n de d t o perf or m p h ysical  e x a mi nati o n a n d meas ure vital  si g ns  ( bl o o d press ure 
a n d p ulse rate) pri or t o t h e bl o o d sa m pli n gs. 
Cali brati o n  certificat es  /  e vi de nce  of  e q ui p me nt  mai nte na nce f or  the  bel o w- liste d 
e q ui p me nt use d t o perf or m st u d y assess me nts m ust be a vaila ble pri or t o t he scree ni n g of 
t he first s u bject. Cali br ati o n certificates of ot her e q ui p me nt m ust be a vaila ble as per l ocal 
re q uire me nts. 
•  Te m perat ur e  meas ur e me nt  de vices  f or  st u d y  treat me nt  st ora ge  area  a n d  freezer  use d 
f or P K sa m ples st ora ge. 
•  Verif y N o w ®  d e vices.  
7. 2. 1  De m o gr a p hics / b aseli ne c h ar acteristics  
D e m o gra p hic  a n d  b aseli ne  c haracteristic  data  t o  be  c ollecte d  o n  all s u bjects,  i ncl u di n g 
a ge, se x, race, a n d et h ni cit y. Rele v a nt me dical hist or y / c urre nt me dical c o n diti o ns (e. g., 
c hr o nic a n d o n g oi n g ac ute c o n diti o ns, seri o us past c o n diti o ns)  prese nt bef ore pr o vi di n g 
i nf or me d  c o nse nt  will  be  rec or d e d  o n  t he  me dical  hist or y eC R F  f or m .  W here  p ossi ble, 
dia g n oses a n d n ot s y m pt o ms will be rec or de d. 
C haracteristics  of  t he  q u alif yi n g  MI  are  of  s pecific i nterest a n d will  be  ca pt ure d  o n a 
de dicate d  eC R F f or m. T h e y  i n cl u de: 
•  S T E MI/ N S T E MI , Date/ti me of s y m pt o m o nset, TI MI ris k s c ore [A p pe n di x 1 ], Killi p 
class [A p pe n di x 2 ]. 
•  Pr oce d ures p erf or me d beca use of t h e q ualif yi n g MI (e. g., a n gi o gra p h y, P CI) . 
T he  f oll o wi n g  e v e nts  ar e  of  s p ecific  i nterest  f or  t his  st u d y  a n d  m ust  be  re p orte d  i n  t he 
Me dical Hist or y f or m : 
•  MI ( pri or t o t he q ualif yi n g MI). 
•  Str o ke a n d tra nsie nt isc h e mic attac k. 
•  P CI or c or o nar y arter y b y p ass graft . 
•  Peri p heral vas c ular s ur ger y . 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 4 3 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
F or  s u bjects  w h o  faile d  scree ni n g,  at  least t he  f oll o wi n g  data  will  be  rec or de d  i n  t he 
eC R F if a vaila ble:  
•  B aseli ne d e m o gra p hics a n d p h ysical c haracteristics (i.e., a ge, race/et h nicit y, se x) . 
•  Reas o n f or scree ni n g fail ure.  
•  A Es a n d S A Es.  
7. 2. 2  Effic ac y assess me nts  
N ot a p plica ble.  
7. 2. 3  P h ar m a c o ki netic a n d p h ar m a c o d y n a mic ass ess me nts  
7. 2. 3. 1  P h ar m ac o ki netic assess m e nts  
7. 2. 3. 1. 1  Pr oce d ures f or bl o o d s a m pli n g 
Bl o o d  will  be  c ollecte d  b y  direct  ve ni p u nct ure  or  via  a n  i. v.  cat heter  place d  i n  a n 
a ntec u bital vei n i n t h e ar m i n a 4 m L M o n o vette ®  or e q ui vale nt t u bes c o nt ai ni n g et h yl e ne 
dia mi ne tetra -acetic aci d ( E D T A).  
P K  bl o o d  sa m ples  ha ve  t o  be  pr ocesse d  wit hi n  3 0  mi n  of  c ollecti o n.  I nstr ucti o ns 
re gar di n g sa m ple  c ollecti o n, pr ocessi n g, la b eli n g, a n d st ora ge c o n diti o ns  are detaile d i n 
t he la b orat or y ma n u al. 
T he ti me p oi nts f or P K assess me nt bl o o d sa m ples are des cri be d i n  T a ble 2.  
T he date a n d e x act act u al cl oc k ti me of c ollecti o n of eac h bl o o d sa m ple will be e ntere d i n 
t he e C R F. 
7. 2. 3. 1. 2  Bi o a n alysis 
T he  a n al ysis  of  A C T -2 4 6 4 7 5  i n  plas ma  will  be  perf or me d  usi n g  a  vali date d  li q ui d 
c hr o mat o gra p h y c o u ple d t o ta n de m mass s pectr o m etr y assa y.  
T he f oresee n l o wer li mit of q u a ntificati o n is 1  n g/ m L. C o nce ntrati o ns will be calc ulat e d 
b y i nter p olati o n fr o m a cali brati o n c ur ve. 
7. 2. 3. 2  P h ar m ac o dy n a mic assess m e nts 
7. 2. 3. 2. 1  Pr oce d ures f or bl o o d s a m pli n g 
T he  differe nt ti me p oi nts f or P D bl o o d sa m ples c ollecti o n are d etaile d i n  Ta ble 2.  
W he n  a p plica ble,  t he  bl o o d  sa m ples  f or  P D  ass ess me nts  are  t o  be  prefer a bl y  c ollecte d 
first,  f oll o we d  b y  bl o o d  sa m ples  f or  P K  t he n  bl o o d  sa m ples  f or  safet y  assess me nts.  A 
2 m L v ol u me of bl o o d nee ds t o be discar d e d pri or t o c ollecti o n of t he P D bl o o d sa m ples. 
P D bl o o d sa m ples will be c ollect e d b y direct ve ni p u nct ure or via a n i. v. cat heter place d i n 
a n a ntec u bital or l ar ge f orear m v ei n i n t he ar m, usi n g 1 8 – 2 1 ga u ge nee dl es.  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 4 4 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
O ne  bl o o d  sa m ple  will  be  dra w n  i nt o  3  m L  v ac u u m  t u bes  f or  eac h  Verif y N o w ®  assa y. 
C ollecti o n  t u bes  
will  c o ntai n  p he n ylal a ni ne - pr oli ne-ar gi ni ne-c hl or o met h yl ket o ne 
( P P A C K) as a n a ntic oa g ula nt. T he platelet a g gre gati o n ass a ys m ust be perf or me d wit hi n 
1 h  of  bl o o d  c ollecti o n.  T he  date  a n d  t he  e x act  act ual  cl oc k  ti me  of  c oll ecti o n  of  eac h 
bl o o d sa m ple (i ncl u di n g t he u nsc he d ule d o nes, if a n y) will be e ntere d i n t h e e C R F.  
Detaile d ha n dli n g i nstr ucti o ns f or P D sa m ples are pr o vi de d i n t he la b orat or y ma n u al. 
7. 2. 3. 2. 2  Bi o a n alysis 
A D P -i n d uce d platelet a g gr e gati o n will be e val u ate d b y usi n g V erif y N o w®  met h o d. 
T he  3  m L  bl o o d  sa m ple  will  be  i nserte d  i nt o  t he  cali brat e d  Verif y N o w ®  s yste m. 
Platelet -i n d uce d a g gr e gati o n is meas ure d wit h A D P as t he a g o nist. T he ass a y will be r u n 
acc or di n g  t o  t h e  ma n uf act urer  i nstr ucti o ns.  T h e  Verif y N o w ®  s yste m  re p orts  platelet 
a g gre gati o n as P R U. 
T he  Verif y N o w ®  s yst e m  ma y  be  use d  wit h  2  differe nt  tests  de pe n di n g  o n  l ocal 
a vaila bilit y:  
•  T he Verif y N o w ®  P 2 Y1 2 test re p orts platelet a g gre gati o n as P R U. I n a d diti o n, a sec o n d 
c ha n nel wit h a n i nter nal sta n dar d c o nsisti n g of t hr o m bi n rece pt or a g o nists is use d f or 
calc ulati o n of t he p erce nt of I P A. W he n a vaila ble, t he use of Verif y N o w ®  P 2 Y1 2 test is 
preferre d.  
•  T he Ve rif y N o w®  P R U test d oes n ot ha ve a n i nter nal sta n dar d a n d o nl y re p orts platelet 
a g gre gati o n as P R U. It is gl o ball y a vaila ble a n d will be use d w here t he Verif y N o w ®  
P 2 Y 1 2 test is n ot a vaila ble. 
7. 2. 4  S af et y assess me nts  
T he defi niti o ns, re p orti n g, a n d f oll o w- u p of A Es a n d S A Es are d escri b e d i n Secti o n  9.  
7. 2. 4. 1  P hysic al e x a mi n ati o n  
P h ysical  e x a mi nati o n will  be  perf or me d  acc or di n g  t o  site  sta n d ar d  m e dical  practice  f or 
s u bjects wit h A MI . 
Ot her e x a ms will be perf or me d if i n dicate d , b ase d o n me dical hist or y a n d/ or s y m pt o ms. 
I nf or mati o n f or all p h ysi cal e x a mi nati o ns m ust be i ncl u de d i n t he s o urce d oc u me ntati o n 
at t he st u d y site.  T he o bser vati o ns will n ot be directl y re p orte d i n t he eC R F. Cli nicall y 
rele va nt fi n di n gs t hat are prese nt pri or t o pr o vi di n g i nf or me d c o ns e nt, m ust be rec or de d 
o n t he Me dical Hist or y e C R F f or m. P h ysical e x a mi nati o n fi n di n gs ma de after pr o vi di n g 
i nf or me d c o nse nt t h at meet t he d efi niti o n of a n A E [ Secti o n  9. 1. 1] m ust be rec or de d o n 
t he A E f or m of t he e C R F.  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 4 5 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
7. 2. 4. 2  Vit al si g ns  
S yst olic a n d diast olic bl o o d press ure a n d p ulse rat e wi ll be meas ure d i n s u bjects i n s u pi ne 
or  sitti n g  p ositi o n . It  is  rec o m me n de d t o  use  th e  sa me  p ositi o n  a n d  sa me  ar m  f or  all 
meas ure me nt s of t h e sa m e s u bject.  
7. 2. 4. 3  Wei g ht a n d h ei g ht 
If h ei g ht a n d wei g ht ca n n ot be meas ure d d ue t o s u bject’s c o n diti o n, it is acce pta bl e t o use 
i nf or mati o n pr o vi de d b y t he s u bject or t o ta ke it fr o m s u bject’s me dical c h art if a vaila ble. 
7. 2. 5  L a b or at or y assess me nts 
7. 2. 5. 1  Ty pe of l a b or at ory 
A ce ntral la b orat or y (see ce ntral la b orat or y ma n u al f or c o ntact details) will be use d f or all 
pr ot oc ol- ma n date d  la b or at or y  tests  e x ce pt f or Acti vate d  Cl otti n g  Ti me  w hic h  is  a 
p oi nt- of- care test a n d will be perf or m e d l ocall y. 
E x ce pti o nal  circ u msta nces t hat ma y re q uire  rec or di n g  of  l o cal  la b orat or y  res ults  of  t he 
varia bles  des cri be d  i n S ecti o n 7. 2. 5. 2 ( wit h  c orres p o n di n g  n or mal  ra n ges)  i ncl u de 
missi n g ce ntral la b orat or y r es ults.  
If t he 4 8 h p ost- d ose ce ntral la b orat or y s a m ple is l ost or ca n n ot be a n al yze d f or w hat e ver 
reas o n, t h e i n vesti gat or ma y c ollect a n a d diti o nal sa m ple f or re peat a nal ysis, as dee me d 
me dicall y  nee de d, u nl ess  a  l ocal  la b orat or y  s a m ple  was  c ollect e d  wit hi n  t he  sa m e  ti me  
wi n d o w a n d t hese test r es ults are a vaila ble.  
Ce ntral  la b or at or y  r e p orts  will  be  se nt  t o  t he  i n vesti gat or.  I n  t he  e ve nt  of  s pecifi c 
( pre-d efi ne d) la b or at or y a b n or malities, t he ce ntral la b orat or y will alert s p o ns or pers o n nel 
a n d  t he  c o ncer ne d  site   pers o n nel.  Al ert  fl a gs  t hat  will  tri g ger  s uc h  n otificati o ns  are 
dis pla ye d i n t he la b orat or y ma n u al. 
All la b orat or y r e p orts m ust be re vie we d, si g ne d, a n d date d b y t he i n vesti gat or or dele gate  
wit hi n  1 0  w or ki n g  d a ys  of  recei pt  a n d  file d  wit h  t he  s o urce  d o c u me ntati o n.  T he 
i n vesti gat or/ del e gate m ust i n dicate o n t he la b orat or y re p ort w het her a b n or mal val ues are 
c o nsi dere d  cli nicall y  rel e va nt  or  n ot.  Cli nicall y  rele va nt  la b orat or y  fi n di n gs  t hat  are 
k n o w n  at  t he  ti me  of pr o vi di n g i nf or me d  c o ns e nt  m ust  be  rec or d e d  o n  t he Me dical 
H ist or y f or m of t he eC R F. A n y cli nicall y rele va nt la b orat or y a b n or malities detecte d after 
pr o vi di n g i nf or me d  c o nse nt  m ust  be  re p orte d  as  a n  A E  or  S A E  as  a p pr o priate  [see 
Secti o n  9 ], a n d m ust be f oll o we d u ntil t he val ue ret ur ns t o wit hi n t he n or mal ra n ge or is 
sta ble, or u ntil t he c ha n ge is n o l o n ger cli nicall y rele va nt.  
Details  a b o ut  t he  c ollecti o n,  sa m pli n g,  st ora ge,  s hi p me nt  pr oce d ures,  a n d re p orti n g  of 
res ults a n d a b n or mal fi n di n gs ca n be f o u n d i n t he l a b orat or y ma n u al. 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 4 6 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
7. 2. 5. 2  L a b or at ory tests 
He mat ol o g y  
•  He m o gl o bi n ( g/ L) 
•  H e mat ocrit  ( L/ L) 
•  Er yt hr o c yte c o u nt ( 1 0 1 2/ L) 
•  Le u k o c yte c o u nt wit h differe ntial c o u nts ( 1 09/ L) 
•  Platelet c o u nt  ( 1 09/ L) 
C oa g ulati o n tests (test perf or me d l ocall y) 
•  Acti vate d cl otti n g ti me (s ec)  
Cli nical c he mistr y  
•  Ala ni ne a mi n otra nsf eras e ( U/ L)  
•  As partate a mi n otra nsferase ( U/ L)  
•  Al kali ne p h os p hatase ( U/ L) 
•  T otal a n d direct bilir u bi n ( μ m ol/ L) 
•  Creati ni ne ( μ m ol/ L)  
•  Creati ni ne cleara n ce ( e G F R) e sti mate d wit h C oc k cr oft-G a ult f or m ula.  
•  Bl o o d urea nitr o ge n ( m m ol/ L) 
•  Uric aci d  ( μ m ol/ L) 
•  S o di u m, p otassi u m, c hl ori de, calci u m ( m m ol/ L) 
•  A l b u mi n ( g/ L) 
Car diac e nz y mes  
•  Hi g h se n siti vit y tr o p o ni n T 
8  
S T U D Y C O M P L E TI O N A N D P O S T- S T U D Y T R E A T M E N T/ M E DI C A L 
C A R E 
8. 1  St u d y c o m p leti o n 
A  s u bject  w h o has  recei ve d  st u d y treat me nt a n d c o m pleted t he E O S assess me nts  is 
c o nsi dere d t o ha v e c o m plete d t he st u d y. 
8. 2  Pre m at ure wit h dr a w al fr o m st u d y 
S u bjects ma y v ol u ntaril y wit h dra w fr o m t he st u d y wit h o ut j ustificati o n f or a n y reas o n at 
a n y ti me. S u bjects ar e c o nsi dere d wit h dra w n if t he y stat e a n i nte nti o n t o wit h dra w fr o m 
f urt her partici pati o n i n all c o m p o ne nts of t he st u d y (i.e., wit h dra w al of c o nse nt), if t he y 
die,  or  ar e  l ost  t o  f oll o w -u p.  If  a  s u bject  wit h dra ws  c o ns e nt,  n o  f urt h er  data  will  be 
c ollecte d  i n  t he eC R F  fr o m  t he  d ate  of  wit h dra wal  o n war d.  T he  i n v esti gat or  ma y 
wit h dra w a s u bject fr o m t he st u d y ( wit h o ut re gar d t o t he s u bject’ s c o nse nt) if, o n bal a nce, 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 4 7 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
he/s he  belie v es  t hat  c o nti n ue d  partici pati o n  i n  t he  st u d y  w o ul d  b e  c o ntrar y  t o  t he  b est 
i nterests  of  t he  s u bject.  Wit h dra wal  fr o m  t he  st u d y  ma y  als o  res ult  fr o m  a  decisi o n  b y 
s p o ns or f or a n y r eas o n, i ncl u di n g pre mat ure t er mi nati o n or s us pe nsi o n of t he st u d y. 
If  pre m at ure  wit h dr a wal  occ urs  f or  a n y  reas o n,  t he  reas o n  (if  k n o w n)  f or  pre m at ure 
wit h dra wal  fr o m t he st u d y,  al o n g wit h  w h o ma d e  t he decisi o n  (s u bject, i n vesti gat or, or 
s p o ns or pers o n nel), m ust be rec or de d i n t he e C R F, if k n o w n. 
T he  i n vesti gat or  m ust  pr o vi de  f oll o w -u p  m e dical  care  f or  all  s u bjects  w h o  are 
pre mat urel y wit h dr a w n fr o m t he st u d y, or m ust refer t he m f or a p pr o priat e o n g oi n g care, 
as descri be d i n Secti o n  8. 4. 
8. 3  Pre m at ure ter mi n ati o n or s us p e nsi o n of t he st u d y 
T he  s p o ns or  reser v es  t he  ri g ht  t o  ter mi nate  t he  st u d y  at  a n y  ti me  gl o ball y  or  l ocall y. 
I n v esti gat ors ca n t er mi nate t he partici pati o n of t heir site i n t he st u d y at a n y time.  
If  a  st u d y  is  pre mat ur el y  s us pe n d e d  or  ter mi nat e d, t he sp o ns or/ del e gate  will  pr o m ptl y 
i nf or m  t he  i n vesti gat ors,  t he  I E Cs/I R Bs,  a n d  healt h  a ut h orities,  as  a p pr o priate,  a n d 
pr o vi de t he reas o ns f or t h e s us pe nsi o n or ter mi nati o n. 
If t he st u d y is s us pe n de d or pre mat urel y t er mi nat e d f or a n y reas o n, t he i n vesti gat or – i n 
a gree m e nt  wit h s p o ns or  – m ust  pr o m ptl y  i nf or m  all  e nr olle d  s u bjects  a n d  e ns ure  t heir 
a p pr o priate  treat me nt  a n d  f oll o w -u p,  as  descri be d  i n  Secti o n  8. 4. T he  s p o ns or/ dele gate 
ma y  i nf or m  t he  i n v esti gat or  of  a d diti o nal  pr oce d ures  t o  be  f oll o we d  i n  or der  t o  e ns ure 
t hat a de q uate c o nsi der ati o n is gi ve n t o t he pr otecti o n of t he s u bjects’ i nterests. 
I n  a d diti o n,  if  t he  i n vesti gat or  s us p e n ds  or  ter mi nates  a  st u d y  wit h o ut  pri or  a gree me nt 
fr o m sp o ns or, t he i n vesti gat or m ust pr o m ptl y i nf or m sp o ns or pers o n nel a n d t he I E C/I R B, 
a n d pr o vi de b ot h wit h a detaile d writte n e x pla nati o n of t he ter mi nati o n or s us pe nsi o n. 
If  t he  I E C/I R B  s us pe n ds  or  ter mi nates  its  a p pr o val  /  fa v ora ble  o pi ni o n  of  a  st u d y,  t he 
i n vesti gat or  m ust  pr o m ptl y  n otif y sp o ns or  pers o n nel  a n d  pr o vi de  a  d etaile d  writte n 
e x pla nati o n of t he ter mi nati o n or s us pe nsi o n. 
8. 4  Me dic al c a re of s u bje cts after st u d y c o m pleti o n / wit h dr a w al fr o m st u d y 
T he s u bject ’s sta n dar d of care will n ot be affecte d b y st u d y partici pati o n. F or t his P K/ P D 
a n d saf et y st u d y, s u bjects will recei ve 1 si n gle a d mi nistrati o n of st u d y treat me nt o n t o p of 
t heir sta n dar d of car e. 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 4 8 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
9  
S A F E T Y D E FI NI TI O N S A N D R E P O R TI N G R E Q UI R E M E N T S 
9. 1  A d verse e v e nts  
9. 1. 1  Defi niti o n of a d verse e ve nts  
A n  A E  is  a n y u nt o war d  me dical  occ ur re nce,  i.e.,  a n y  u nfa v ora ble  a n d  u ni nte n de d  si g n, 
i ncl u di n g  a n  a b n or mal  l a b orat or y  fi n di n g,  s y m pt o m,  or  disease  t hat  occ urs  i n  a  s u bject 
d uri n g t he c o urs e of t he st u d y, w het her or n ot c o nsi dere d b y t he i n vesti gat or as relate d t o 
st u d y treat me nt. 
A Es  i ncl u de: 
•  E x acer bati o n of a pre -e xisti n g disease.  
•  I n crease  i n  fre q ue n c y  or  i nte nsit y  of  a  pre-e xisti n g  e pis o dic  disease  or  me dical 
c o n diti o n. 
•  Disease  or  m e dical  c o n diti o n  detecte d  or  dia g n ose d  d uri n g  t he  c o urse  of  t he  st u d y 
e ve n t h o u g h it ma y h a ve bee n pres e nt pri or t o t he start of t he st u d y. 
•  C o nti n u o us persiste nt disease or s y m pt o ms prese nt at st u d y start t h at w orse n f oll o wi n g 
t he pr o visi o n of i nf or me d c o nse nt. 
•  A b n or mal  assess me nts,  e. g.,  c h a n ge  o n  p h ysical  e x a mi nati o n,  E C G  fi n di n gs,  if  t he y 
re pres e nt a cli nicall y si g nifica nt fi n di n g t h at was n ot prese nt at st u d y start or w orse n e d 
d uri n g t he c o urse of t he st u d y. 
•  La b orat or y  test  a b n or malities  if  t he y  re pres e nt  a  cli nicall y  si g nifica nt  fi n di n g, 
s y m pt o matic  or  n ot,  w hic h  was  n ot  prese nt  at  st u d y  start  or  w orse ne d  d uri n g  t he 
c o urse of t he st u d y. 
9. 1. 2  Defi niti o ns of seri o us a d verse e ve nts  
A n S A E  is  defi ne d  b y  t he  I C H  g ui deli nes  as  a n y  A E  f ulfilli n g  at  l eas t  o ne  of  t he 
f oll o wi n g criteria: 
•  Fatal.  
•  Lif e -t hreate ni n g:  Refers  t o  a n  e ve nt  i n  w hic h  t he  s u bject  was  at  ris k  of  d eat 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 us e d 
deat h ha d it bee n m or e se vere.  
•  Re q uiri n g 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 ulti n g i n persiste nt or si g nifica nt disa bilit y or i nca pacit y.  
•  C o n ge nital a n o mal y or birt h defect. 
•  Me dicall y  si g nifica nt:  Refers  t o  i m p orta nt  me dical  e ve nts  t hat  ma y  n ot  i m me diatel y 
res ult i n deat h, be life-t hreate ni n g, or re q uire h os pitalizati o n b ut ma y be c o nsi dere d t o 
be  S A Es  w h e n,  bas e d  u p o n  a p pr o pri ate  me dical  j u d g me nt,  t h e y  ma y  j e o par dize  t he 
s u bject,  a n d  ma y  re q uire  me dical  or  s ur gi cal  i nter ve nti o n  t o  pre ve nt  o ne  of  t he 
o utc o mes liste d i n t he defi niti o ns a b o ve. 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 4 9 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
T he f oll o wi n g reas o ns f or h os pitalizati o n are n ot c o nsi dere d as S A Es: 
•  H os pitalizati o n f or t he A MI q u alif yi n g f or e ntr y i n t he st u d y. 
•  H os pitalizati o n  f or  c os metic  electi ve  s ur ger y,  or  s ocial  a n d/ or  c o n ve ni e nce  reas o ns 
(i ncl u di n g h os pitalizati o n relate d t o pr ot oc ol pr o ce d ures). 
•  H os pitalizati o n  f or  pre -pla n ne d  (i.e.,  pla n ne d  pri or  t o  i nf or me d  c o nse nt)  s ur ger y  or 
sta n dar d m o nit ori n g of a pre-e xisti n g disease or me dical c o n diti o n t hat di d n ot w orse n, 
e. g., h os pitalizati o n f or c or o nar y a n gi o gra p h y i n a s u bject wit h sta ble a n gi n a pect oris. 
H o we ver,  c o m plicati o ns  t hat  occ ur  d uri n g  h os pitalizati o n  are  A Es  or  S A Es  (e. g.,  if  a 
c o m plicati o n pr ol o n gs h os pitalizati o n). 
9. 1. 3  Defi niti o n of s us pecte d u ne x pecte d seri o us a d verse re acti o n  
T he  e x pecte d ness  of  a n  S A E  is  deter mi ne d  b y  t he  s p o ns or  i n  t he  refere nce  safet y 
i nf or mati o n  ( R SI)  s ecti o n  pr o vi de d  i n  t h e  m ost  rece nt  v ersi o n  of  t he  I B 
[A C T - 2 4 6 4 7 5 I B]. A n y S A E t hat is assesse d as relate d a n d u ne x pecte d a gai nst t he R SI is 
k n o w n as a s us pecte d u n e x pecte d seri o us a d verse reacti o n ( S U S A R). 
9. 1. 4  Defi niti o n of tre at me nt -e mer g e nt a d vers e e ve nt  
A treat me nt -e mer ge nt A E  ( T E A E) is a n y A E te m p orall y ass ociat ed wit h t he use of st u d y 
treat me nt u ntil 4 8 h after st u d y treat me nt a d mi nistrati o n w het her or n ot c o nsi dere d b y t he 
i n vesti gat or as relate d t o st u d y treat me nt. T he 4 8 h wi n d o w f or T E A Es has bee n defi ne d 
t o i ncl u de at least 5 half-li ves of A C T- 2 4 6 4 7 5. 
9. 1. 5  I nte nsit y of a d verse e ve nts 
T he i nte nsit y of cli nical A Es is gra d e d o n a t hree -p oi nt scale (mil d, m o derate, se vere ) as 
f oll o ws: 
 Mil d  
T he e v e nt ma y be n oticea ble t o t he s u bject. It d o es n ot us uall y i nfl ue nce dail y acti vities, 
a n d n or mall y d o es n ot re q uire i nter ve nti o n. 
 M o der ate  
T he e ve nt ma y ma k e t he s u bject u nc o mf orta ble. Perf or ma nce of dail y acti vities ma y be 
i nfl ue nce d, a n d i nter ve nti o n ma y be n ee d e d. 
 Se vere  
T he  e v e nt  ma y  ca us e  n oticea ble  disc o mf ort,  a n d  us uall y  i nterferes  wit h  d ail y  acti vities. 
T he  s u bject  ma y  n ot  be  a ble  t o  c o nti n ue  i n  t he  st u d y,  a n d  treat me nt  or  i nter ve nti o n  is 
us uall y nee de d. 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 5 0 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
A  mil d,  m o derate,  or  se vere  A E  ma y  or  ma y  n ot  be  seri o us.  T hese  ter ms  are  use d  t o 
descri be  t he  i nte nsit y  of  a  s pecific  e ve nt.  Me dical  j u d g me nt  s h o ul d  be  use d  o n  a  
case-b y -cas e basis.  
Seri o us ness,  rat her  t ha n i nte nsit y assess me nt,  deter mi nes  t he  re g ulat or y  re p orti n g 
o bli gati o ns [see Secti o n 9. 3. 2] . 
9. 1. 6  Rel ati o ns hi p t o st u d y tre at me nt  
Eac h A E m ust be assess e d b y t h e i n vesti gat or as t o w het her or n ot t here is a reas o n a ble 
p ossi bilit y of ca usal rel ati o ns hi p t o t he st u d y treat me nt, a n d re p orte d as eit her relat e d or 
u nrelate d.  
9. 1. 7  Rel ati o ns hi p t o pr ot oc ol- m a n d ate d pr oce d ure  
A n A E/ S A E is d efi ne d as relate d t o pr ot o c ol -ma n date d pr o ce d ure if it a p p ears t o ha ve a 
reas o na bl e  p ossi bilit y  of  a  ca usal  relati o ns hi p  t o  eit her  t he  st u d y  d esi g n  or  t o  a 
pr ot oc ol- ma n date d  pr o ce d ure  (e. g.,  disc o nti n uati o n  of  a  s u bject ’s  pre vi o us treat me nt 
lea di n g t o e x acer b ati o n of u n derl yi n g diseas e). T h e deter mi nati o n of t h e li keli h o o d t hat a 
pr ot oc ol- ma n date d pr oce d ure ca us e d t he A E/ S A E will be pr o vi de d b y t h e i n vesti gat or. 
9. 2  Ti me peri o d a n d fre q ue nc y f or A E/ S A E ass ess me nt a n d f oll o w- u p  
T he occ u rr e nce of a n A E/ S A E ma y c o me t o t he atte nti o n of st u d y p ers o n nel at a n y ti me 
d uri n g  st u d y. D uri n g  t h e st u d y,  t he  i n vesti gat or  will  i n q uire  a b o ut  t he  occ urre nce  of 
A E/ S A Es.  
T he  cli nical  c o urse  of  A Es/ S A Es  will  be  f oll o we d  acc or di n g  t o  l ocal  sta n dar d  me dical  
practices.  
9. 2. 1  F oll o w- u p of a d verse e v e nts  
A Es  still  o n g oi n g  at  t he  E O S m ust  be  f oll o we d  u p  u ntil  t he y  are  n o  l o n ger  c o nsi dere d 
cli nicall y r ele va nt or u ntil sta bilizati o n.  
9. 2. 2  F oll o w- u p of seri o us a d verse e v e nts  
S A Es  still  o n g oi n g at  t he  E O S m ust  be  f oll o we d  u p  u ntil  res ol uti o n  or  sta bilizati o n,  or 
u ntil t he e ve nt o utc o me is pr o vi de d.  
9. 3  Re p orti n g pr oce d ures  
9. 3. 1  Re p orti n g of a d verse e v e nts  
All A Es wit h a n o nset d ate after a s u bject has pr o vi de d  i nf or me d c o nse nt a n d u p t o t he 
E O S m ust be rec or d e d o n s pecific A E f or ms of t h e eC R F.  
I nf or mati o n t o be c ollect e d i n a n A E f or m i n t he eC R F i ncl u des dat e a n d ti me of o nset, 
acti o n ta ke n wit h t he st u d y tr eat me nt, o utc o m e of A E, d ate of res ol uti o n (if a p plica bl e) 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 5 1 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
a n d Pri nci pal  I n vesti gat or ’s  ( PI) assess me nt  of i nte nsit y,  a n d  relati o ns hi p  t o  st u d y 
treat me nt, st u d y d esi g n or pr ot oc ol ma n date d pr oce d ures. 
If i nte nsit y of a n A E c h a n ges d uri n g t h e st u d y, o nl y t he w ors e i nte nsit y  will be re p orte d 
i n t he eC R F.  
F oll o w- u p  i nf or m ati o n  o n a n o n g oi n g  A E  o bt ai ne d  after  t he  s u bj ect ’s  E O S  will  n ot  be 
c ollecte d i n t he eC R F.  
9. 3. 2  A d diti o n al r e p orti n g pr oce d ures f or  seri o us a d verse e v e nts 
All  S A Es  m ust  be  re p orte d  b y  t he  i n vesti gat or  t o t he s p o ns or’s Gl o bal  Dr u g  Safet y 
de part me nt wit hi n 2 4 h o urs of t he i n vesti gat or’s first k n o wle d ge of t he e v e nt. 
All  S A Es  occ urri n g  after a  s u bject  has  pr o vi de d  i nf or me d  c o nse nt a n d u p  t o  t he  E O S 
m ust  be  rec or de d  o n  a n  S A E  f or m,  re gar dless  of  t he  i n vesti gat or -attri b ute d  ca us al 
relati o ns hi p wit h st u d y tr eat me nt or st u d y-ma n dat e d pr oce d ures.  
T he S A E f or ms m ust be se nt t o t he s p o ns or’s Gl o bal Dr u g Safet y de part me nt (see c o nt act 
details o n t he S A E f or m).  T he i n vesti gat or m ust c o m plete t he S A E f or m i n E n glis h, a n d 
m ust assess t he e ve nt ’s ca usal relati o ns hi p t o t he st u d y treat me nt. 
A n y r ele va nt i nf or m ati o n fr o m s o urce d oc u m e nts re gar di n g t he S A E, e. g., h os pital n otes 
or disc har ge s u m maries, etc., m ust be s u m marize d o n t he S A E f or m.  
F oll o w- u p  i nf or mati o n  a b o ut  a  pre vi o usl y  re p ort e d  S A E  m ust  als o  be  re p orte d  wit hi n 
2 4 h of  recei vi n g  it. T he  s p o ns or’s Gl o bal  Dr u g  Safet y  pers o n nel  ma y  c o ntact  t he 
i n vesti gat or t o o btai n f urt her i nf or mati o n. 
If t he s u bject is h os pitali ze d i n a h os pital ot her t h a n t he st u d y site, it is t he i n vesti gat or’s 
res p o nsi bilit y  t o  c o ntact  t his  h os pital  t o  o btai n  all  S A E-rele va nt  i nf or mati o n  a n d 
d oc u me ntati o n. 
F oll o w- u p  i nf or mati o n  o n  a n  o n g oi n g  S A E  o btai ne d  after  a  s u bject ’s  E O S  m ust  be 
re p orte d  t o  t he  s p o ns or’s  Gl o bal  Dr u g  Safet y  d e part me nt,  b ut  is  n ot  rec or de d  i n  t he 
eC R F.  
Ne w S A Es o cc urri n g aft er t he E O S m ust be re p orte d t o t he s p o ns or’ s Gl o b al Dr u g Safet y 
de part me nt wit hi n 2 4 h  of t he i n vesti gat or ’s k n o wle d ge of t h e e v e nt, o nl y if c o nsi dere d 
b y t he i n vesti gat or t o b e ca usall y rel ate d t o pre vi o us e x p os ure t o t he st u d y treat me nt. 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 5 2 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
9. 3. 3  A d diti o n al re p orti n g pr oce d ures f or s us pecte d u ne x pe cte d seri o us a d verse 
re acti o ns  
A n y  S U S A R  [ see  defi niti o n  i n  Secti o n 9. 1. 3]  will  be  re p orte d  b y  t he  s p o ns or  t o 
c o ncer n e d  healt h  a ut h orities  (i ncl u di n g  t he  E u dra Vi gila nce  data b ase  if  t he  st u d y  is 
c o n d ucte d i n E ur o p e), I E Cs/I R Bs a n d i n v esti gat ors. 
9. 4  Re p orti n g of st u d y tre at me nt o v er d ose, mis use, a b use a n d err ors 
St u d y treat me nt o ver d os e ( d efi ne d as hi g her t ha n t he d ose of 1 6 m g ), a n d st u d y treat me nt 
err ors will be re p orte d as a n A E w he n ass ociate d wit h si g ns or s y m pt o ms. 
I n  a d diti o n,  st u d y  treat me nt  err ors  m ust  be  d oc u me nte d  i n  t he  st u d y  dr u g  l o g  of  t he 
eC R F.  
Mis use a n d a b use of t h e st u d y treat me nt will be re p orte d as a n A E. 
9. 5  St u d y s afet y m o nit ori n g 
St u d y  safet y  i nf or mati o n  ( A Es,  S A Es,  la b orat or y  val ues,  vital  si g ns,  a n d st u d y-s pecific 
e x a mi nati o ns  as  re q uire d)  is  m o nit ore d  a n d  re vie we d  o n  a  c o nti n u o us  basis  b y  t he 
s p o ns or’s  cli nical tea m (i n  c har ge  of  e ns uri n g  s u bjects’ safet y  as  w ell  as  data  q ualit y). 
T he s p o ns or ma y re q uest a d diti o nal data pertai ni n g t o t he di a g n ostic w or k- u p of a n A E or 
S A E  (e. g., E C Gs, me dical  i ma gi n g,  l ocal  la b orat or y  v al ues)  f or  t he  p ur p ose  of 
m o nit ori n g saf et y.  S uc h  a d diti o nal  data  ma y  be  s hare d  wit h  e xter nal  e x perts fr o m  t h e 
i n de pe n de nt saf et y e ve nt c o m mittee [see S ecti o n 3. 3] . 
1 0  S T A TI S TI C A L M E T H O D S 
All statistical a nal yses will be c o n d ucte d b y s p o ns or or b y desi g nate d C R Os s u per vise d 
b y s p o ns or. 
A statistical a nal ysis p la n ( S A P) will pr o vi de f ull details of t he  a nal ys es, data dis pla ys, 
a n d al g orit h ms t o be use d f or data d eri vati o ns. 
A n y  de viati o n(s)  fr o m  t he  statistical  pla n  descri be d  hereafter  will  be  descri be d  a n d 
j ustifie d i n t he S A P or i n t he cli nical st u d y re p ort ( C S R), as a p pr o priate. 
1 0. 1  A n al ysis sets 
1 0. 1. 1  S cree ne d a n al ysis set  
T he  Scree ne d  a n al ysis  s et  i ncl u des  all  s u bjects  w h o  are  s cree ne d  a n d  h a ve  a  s u bject 
i de ntificati o n n u m ber. 
1 0. 1. 2  R a n d o mize d a n al ysis set 
T he  R a n d o mize d  a nal ysis  set  i ncl u des  all  s u bjects  w h o  ha ve  bee n  assi g ne d  t o  a  st u d y 
treat me nt. 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 5 3 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
1 0. 1. 3  F ull a n al ysis s et 
T he F ull a nal ysis set ( F A S) i ncl u des all  ra n d o mize d s u bjects w h o ha ve bee n a d mi nistere d  
t he st u d y treat me nt. 
F or a nal yses  perf or me d  o n  t he  F AS s u bjects  will  be  e v al uate d  acc or di n g  t o  t he  act ual 
treat me nt t he y recei ve d, w hic h ma y differ fr o m t h e ra n d o ml y assi g ne d treat me nt. 
1 0. 1. 4  M o difie d F ull a n al ysis s et  
T he m o difie d F A S  ( m F A S) i ncl u des all s u bjects fr o m t he F A S w h o ha ve a n assess me nt  
of t he pri mar y e n d p oi nt, i.e., P R U meas ure d 3 0 mi n utes after st u d y dr u g a d mi nistrati o n. 
1 0. 1. 5  Per - pr ot o c ol a n al ysis set 
T he Per -pr ot oc ol a n al ysis s et ( P P S) c o m prises all s u bjects fr o m t he F A S w h o c o m plie d 
wit h  t he  pr ot oc ol  s ufficie ntl y  t o all o w  a d e q uat e  esti mat i o n  of t h e  treat me nt  effects. 
Criteria  f or  s ufficie nt  c o m plia nce  i ncl u de  e x p os ure  t o  treat me nt,  a vaila bilit y  of ke y 
e n d p oi nts meas ure me nts a n d a bse n ce of maj or pr ot oc ol de viati o ns t hat ha ve a n i m pact o n 
t he treat me nt effect a n d will be s pecifie d i n t he S A P . 
1 0. 1. 6  S af et y s et 
T he saf et y a nal ysis  s et ( SA F ) i ncl u d es  all  s u bjects  w h o  recei ve d  at  least  o ne  d ose  of 
st u d y treat me nt.  
S u bjects  will  be  e val uate d  acc or di n g  t o  t he  act u al treat me nt t he y  recei v e d,  w hic h  ma y 
differ fr o m t he ra n d o ml y assi g ne d treat me nt. 
1 0. 1. 7  Ot her a n al ysis sets 
1 0. 1. 7. 1  P h ar m ac o ki netic a n alysis set  
T he  P K  a nal ysis  s et  i ncl u des  all  s u bjects  i n  t he S A F  w h o  ha ve  at  least  o ne  P K  sa m ple 
c ollecte d after a d mi nistrati o n  of st u d y treat me nt. 
1 0. 1. 8  Us a ge of t he a n al ysis sets 
T he a nal ysis of P D e n d p oi nts will be perf or me d o n t he m F A S w hile se nsiti vit y a n al ys es 
will be c o n d ucte d usi n g s a me e n d p oi nts as s pecifie d i n S ecti o n 1 0. 3 o n t he F A S a n d P P S.  
Safet y a nal yses will be  perf or me d o n t h e S A F b ase d o n act ual st u d y treat me nt recei ve d. 
S u bject listi n gs will be b ase d o n t he S A F , u nl ess ot her wise s pecifie d. S u bj ect dis p ositi o n 
will be descri be d f or t he Scree ne d  anal ysis set.  
Ta ble 3 descri bes t he a n al ysis sets use d f or t h e a nal ysis of eac h data s et.  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 5 4 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
T a ble 3  
Us a ge of a n al ysis d at asets 
A n al ysis  
Scree ne d set  R N D  
F A S  m F A S  P P S  
S A F  P K set  
S u bj ect dis p ositi o n  
X  
 
 
 
 
 
 
Baseli ne a n d disease 
c haracteristics 
  
( x)  
X  
  
( x)  
  
 
Pre vi o us a n d c o nc o mita nt 
me dicati o n  
  
  
X  
  
  
  
 
St u d y treat me nt e x p os ure  
 
 
X  
 
( x) 
 
 
P D e n d p oi nt  a nal yses 
 
 
( x) 
X  
( x) 
 
 
Safet y a n d t olera bilit y a nal yses  
 
 
 
 
 
X  
 
P K data a nal ysis 
 
 
 
 
 
 
X  
N ote: 1: Selecte d safet y p ara meters,  X: mai n a n al ysis, ( x): se nsiti vit y a n al ysis t o b e c o n d u cte d o nl y if > 1 0 % differe nce 
of set size wit h set use d f or mai n a n al ysis. R N D: Ra n d o mize d set; F A S: F ull a n al ysis s et; m F A S: m o difie d F ull 
a n al ysis set; P D: p h ar mac o d y n a mic; P K: p h ar mac o ki n etic; P P S: P er -pr ot o c ol s et; S A F: Safet y s et. 
1 0. 2  V ari a bles 
T he a bs ol ute  c h a n ge  fr o m  b aseli ne  t o  ti me  T  is  defi ne d  as  t he  al ge braic  differe nce 
bet wee n t he v al ue  o bser v e d at ti me T mi n us t he val ue at baseli ne.  
T he rel ative c h a n ge fr o m b aseli ne t o ti me T is defi ne d as t he rati o of t he a bs ol ute c ha n ge 
fr o m baseli ne t o ti me T o n t he baseli ne val ue. 
U nless s pecifie d ot her wise, t he b aseli ne v al ue  is defi ne d as t he last val ue c ollecte d pri or 
t o ra n d o mizati o n. 
1 0. 2. 1  Pri m ar y effi c ac y v ari a ble(s) 
N ot a p plica ble.  
1 0. 2. 2  Ke y sec o n d ar y effic ac y v ari a bles 
N ot a p plica ble.  
1 0. 2. 3  P h ar m a c o ki netic a n d p h ar m a c o d y n a mic v a ri a bles  
1 0. 2. 3. 1  P h ar m ac o ki netic v ari a bles 
P K para meters will be deri ve d usi n g n o n-c o m part me ntal met h o ds: 
•  C ma x  a n d t ma x  will be liste d b y d ose gr o u p a n d s u bj ect a n d will be s u m marize d b y d os e 
gr o u p. 
•  C ma x  a n d t ma x * will be s u m marize d wit h arit h metic mea n, ge o metric mea n, mi ni m u m, 
me dia n,  ma xi m u m, 
sta n dar d  de viati o n  (S D ), sta n dar d  err or  (S E ), c o efficie nt  of 
variati o n ( C V ; %) , a n d 9 5 % c o nfi de nce i nter val  (CI ) of t he arit h metic a n d ge o metric 
mea ns.  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 5 5 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
( * F or tma x  t he ge o m etric mea n a n d its 9 5 % CI will n ot be calc ulate d). 
•  L o g -tr a nsf or m e d Cma x  val ues will be s u m marize d b y mea n a n d S D of t he l o garit h ms.  
1 0. 2. 3. 2  P h ar m ac o dy n a mic v ari a bles 
T he P D varia bles are (as meas ure d b y V erif y N o w ® ): 
•  t he a bs ol ute P R U val ue, 
•  t he perce nta ge of i n hi biti o n of platelet a g gre gati o n (if P 2 Y1 2 test has bee n use d).  
1 0. 2. 4  S af et y v ari a bles 
1 0. 2. 4. 1  A dverse eve nts  
A n A E  is defi ne d as a n y e ve nt t hat is rec or de d o n t he A E eC R F m o d ule re gar dless of t he 
o nset date.  
T E A Es  ar e t h ose A Es wit h o nset date/ti me ≥ date/ti me of st u d y treat me nt a d mi nistrati o n 
a n d ≤ 4 8 h after d ate/ti me  of st u d y treat me nt a d mi nistrati o n. 
T he  ha n dli n g  of  missi n g  or  i nc o m plete  dates/ti me  of  A Es  a n d  assess me nts  will be 
descri be d i n t he S A P. 
1 0. 2. 4. 2  A dverse eve nt of s peci fi c interest : He m orr h a ge 
A n  A E  of  s p eci fic i nter est  (A E SI ) h e m orr ha ge  is  a n y  A E  wit h  a  preferre d  t er m  ( P T) 
bel o n gi n g t o t he sta n dar d ise d Me d D R A q uer y “ Hae m orr ha ge ( E x cl. la b orat or y ter ms)”. 
T E A Es  of s peci fic inter est ( T E A E SI s) are t h ose A E SIs wit h o nset d ate/ti me ≥ date/ti me 
of first st u d y tr eat me nt a d mi nistrati o n a n d ≤ 4 8 h after d ate/ti me of last st u d y treat me nt 
a d mi nistrati o n.  
1 0. 2. 4. 3  L a b or at ory d at a 
La b orat or y  a n al yses  ar e  base d  o n  data  recei ve d  fr o m  t he  ce ntral  lab orat or y [see 
S ecti o n 7. 2. 5. 2].  All c ollecte d la b orat or y  data  are  ta k e n  i nt o  acc o u nt  re gar dless  of 
w het her t he y c orr es p o n d t o sc he d ule d or u nsc h e d u le d assess me nts. 
E O S  l a b or at ory  test ref ers  t o  t he  la b orat or y  t est  perf or me d  at  t he  4 8 h  p ost -d ose  ti me 
p oi nt. 
F or eac h c o nti n u o us la b orat or y vari a ble , t he f oll o wi n g will be s u m marize d: 
•  A bs ol ute val ue at eac h ti me p oi nt, 
•  A bs ol ute c ha n ge fr o m baseli ne t o eac h meas ure d ti me p oi nt,  
•  Treat me nt -e mer ge nt  mar ke d  l a b orat or y  a b n or malities 
(i.e., sa m ples date/ti me 
≥ date/ti me  of  first  st u d y  treat me nt  a d mi nistrati o n  a n d  ≤  4 8  h  after  d ate/ti me  of  last 
st u d y treat me nt a d mi nistrati o n). 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 5 6 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
F or cate g ori cal la b or at or y v aria bles , t h e p r o p orti o n of s u bjects b y cate g or y at eac h ti me 
p oi nt will be s u m marize d . 
U nless state d ot her wise, n o i m p utati o n f or missi n g la b orat or y val u es will be perf or me d.  
1 0. 2. 4. 4  Vit al si g ns  
•  A bs ol ute val ue s f or vital si g ns  (s yst olic a n d diast olic arterial bl o o d press ure a n d p ulse 
rate) at eac h assesse d ti m e p oi nt d uri n g t he st u d y. 
•  Relati ve c ha n ge fr o m bas eli ne t o eac h meas ure d ti me p oi nt i n vital si g ns. 
1 0. 3  Descri pti o n of st atisti c al a n al yses 
All  a nal yses  will  be  c o n d ucte d  b y  treat me nt  gr o u p,  i.e. , A C T - 2 4 6 4 7 5  8 m g  a n d  
A C T - 2 4 6 4 7 5 1 6 m g .  
1 0. 3. 1  O ver all testi n g str at e g y  
T he  st u d y  is  i nte n de d  t o  assess  t he I P A 3 0  mi n  after  a  si n gle s.c. i njecti o n  of 
A C T - 2 4 6 4 7 5. 
It will be declare d t o b e p ositi ve wit h re gar d t o t he pri mar y o bjecti ve  if f or at least o ne of 
t he t w o teste d d oses of A C T - 2 4 6 4 7 5, t he c orres p o n di n g n ull h y p ot hes es is rejecte d at t he 
0. 0 2 5 al p ha le vel. 
N o i m p utati o n will be c o nsi dere d f or h a n dli n g missi n g val ues i n t he mai n a nal ysis of P D.  
Im p utati o n s ma y b e perf or me d i n se nsiti vit y /e x pl orat or y a nal yses,  if  dee me d  necessar y, 
e. g., m or e t ha n 1 0 % missi n g val ues at a gi ve n ti me p oi nt. 
1 0. 3. 2  A n al ysis of effic ac y v ari a ble(s) 
N ot a p plica ble.  
1 0. 3. 3  A n al ysis of t he p h ar m a c o d y n a mic v a ri a bles 
All a nal ys es of P D varia bles will be perf or me d usi n g t he m F A S as pri mar y a n al ysis set, 
a n d base d o n t h e act u all y a d mi nistere d treat me nt, w hic h ma y differ fr o m t he o ne assi g ne d 
t hr o u g h t he ra n d o mizati o n pr ocess. 
T he  st u d y  is  desi g n e d t o  de m o nstrate t hat  A C T-2 4 6 4 7 5  e na bles a lar ge  pr o p orti o n  (a 
tar get  of  8 5 %)  of  t he  e nr olle d  s u bjects t o ac hie ve  a  cli nicall y mea ni n gf ul  le vel  of  I P A, 
i.e., P R U < 1 0 0. 
1 0. 3. 3. 1  Hy p ot heses a n d st atistic al m o del 
T he pri mar y o bjecti ve is t o assess I P A 3 0 mi n  after a si n gl e s.c. i njecti o n of A C T- 2 4 6 4 7 5 
i n s u bjects wit h A MI recei vi n g c o n v e nti o nal a ntit hr o m b otic treat me nt (e. g., as piri n, oral 
P 2 Y 1 2 rece pt or a nta g o nists, a ntic oa g ul a nts). 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 5 7 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
I n or d er t o ac hi e ve t his o bjecti ve, t he testi n g strate g y will be t o test t he treat me nt effect 
( usi n g  t he  pr o p orti o n p of  res p o n d ers,  i.e. , ac hie vi n g  P R U  <  1 0 0) f or eac h  of  t he  t w o 
treat me nt ar ms c o nsi d eri n g t he f oll o wi n g h y p ot hese s:  
H 0 H D : pH D  ≤ 5 0 % 
vs   
H 1 H D: pH D   ≥ 8 5 % 
H 0 L D: pL D  ≤ 5 0 %   
vs   
H1 L D: pL D   ≥ 8 5 % 
w here L D is t he l o w er A C T -2 4 6 4 7 5 d ose ( 8 m g), a n d H D t h e hi g h er  A C T -2 4 6 4 7 5 d ose 
( 1 6 m g).  
Eac h of t he t w o n ull h y p ot hes es will be teste d b y a t w o-si de d z-test at a si g nifica nce le v el 
(al p ha)  of  0. 02 5, w hic h  is  a n  o verall  le vel  of  0. 0 5  f or  t he  st u d y l e vel  a n d  a dj uste d  f or 
m ulti plicit y usi n g B o nf er r o ni met h o d. 
1 0. 3. 3. 2  H a n dli n g of missi n g d at a 
S u bject s f or w ho m t he d eter mi nati o n of t h e res p o nse is n ot p ossi ble , i.e., w h o ha ve n ot 
recei v e d  A C T-2 4 6 4 7 5  or wit h 
a missi n g  3 0  mi n   p ost-st u d y  dr u g  a d mi nistrati o n 
assess me nt, will  be re place d ; no i m p utati o n will be c o nsi dere d . 
1 0. 3. 3. 3  M ai n a n alysis 
T he pri mar y statistical a nal ysis will be perf or me d o n t he m F A S p o p ulati o n  f or eac h d ose 
le vel. 
It will c o nsi der t h e treat me nt act uall y recei ve d ( w hic h ma y differ fr o m t h e assi g n e d o ne). 
T he  a n al ysis  of  t h e  pri mar y  e n d p oi nt  will  be  perf or me d  f or  eac h  of  t he  t w o  d oses 
i n de pe n de ntl y, i.e., c o nsi deri n g  2  n ull  h y p ot h es es  ( pr o p orti o n  of  patie nts  ac hie vi n g  a 
res p o nse is less t ha n or e q ual t o 5 0 %) at 0. 0 2 5 t y p e I err or eac h [see Secti o n 1 0. 3. 3. 1].  
T he st u d y will be declar e d p ositi ve wit h re gar d t o t he pri mar y o bj ecti ve, if at least 1 of 
t he 2 n ull h y p ot heses is r ejecte d at 0. 0 2 5 t y p e I err or le vel.  
A o ne -si de d z-test will be c o m p ute d a n d t he 9 5 % CI  of t he pr o p orti o n of res p o n ders will 
be pr o vi de d.  
S u m mar y of res p o nse, i n ter ms of n u m ber ( %) of res p o n di n g s u bj ects, will be pr o vi de d.  
I P A as meas ur e d b y Verif y N o w®  will als o be s u m marize d as a c o nti n u o us varia ble .  
T h ose  s u m maries  will  als o  be  pr o vi d e d  c o nsi d er i n g  t he  a vaila ble  P D  assess me nt ti me 
p oi nts ( 1 5 mi n a n d 6 0 mi n p ost- d ose). 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 5 8 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
1 0. 3. 3. 4  S u p p ortive/se nsitivity a n alyses  
Ass u mi n g  rele v a nt  n u m ber  of  s u bjects  i n  eac h 
S T E MI/ N S T E MI s u b gr o u p,  t he 
c o nsiste nc y  acr oss S T E MI  a n d  N S T E MI s u b gr o u ps  will  be  assesse d b y  testi n g t he 
i nteracti o n effect  of  S T E MI/N S T E MI wit h  treat me nt  d ose o n t h e pri mar y  e n d p oi nt 
a nal ysis .  
A  l o gistic  r e gressi o n  a nal ysis  of  t h e  P D  res p o nse  will  be  perf or me d  usi n g  s u bject, 
A C T -2 4 6 4 7 5 d ose ( 8 m g, a n d 1 6 m g), S T -se g me nt ele vati o n ( S T E MI vs N S T E M I), a ge 
(c o nti n u o us), ge n der ( male, fe male) as c o v ariates. 
F urt her a nal yses will be descri be d i n t he S A P as necessar y.  
1 0. 3. 4  A n al ysis of t he p h ar m a c o ki netic v ari a bles 
Plas ma  c o nce ntr ati o ns  per  ti me  p oi nt  will  be  liste d  b y  d ose  gr o u p  a n d  s u bject,  a n d 
s u m marize d  by  ti me  p oi nt  a n d  d ose  gr o u p  usi n g  arit h metic  a n d  ge o metric  mea n, 
mi ni m u m, me dia n, ma xi m u m, S D, S E, a n d t w o-si de d 9 5 % CI of t he mea ns a n d C V i n %.  
1 0. 3. 5  A n al ysis of t he s af et y v ari a ble(s) 
U nless n ote d ot her wise, t he S A F will be use d f or s u m maries a n d listi n gs of safet y data. 
All safet y a n al ys es will be perf or m e d usi n g t he S A F, base d o n t he act uall y a d mi nistere d 
treat me nt, w hic h ma y differ fr o m t he o ne assi g ne d t hr o u g h t he ra n d o mizati o n pr ocess. 
1 0. 3. 5. 1  A dverse eve nts  
A Es  c o de d  usi n g  t he  m ost  rece nt  versi o n  of Me d D R A  will be  s u m marize d  (fre q ue n c y 
c o u nts  a n d  p erce nta ges)  b y  s yst e m  or ga n  class  a n d/ or  preferre d  ter m,  a n d  ma xi m u m 
i nte nsit y. 
S u m maries will be pr o vi de d  f or t he f oll o wi n g dat a: 
•  T E A Es,  
•  T E A E SIs , 
•  T E A Es relate d t o st u d y tr eat me nt,  
•  Occ urre nce of tr eat me nt -e mer ge nt n o n-s eri o us A Es, 
•  Treat me nt -e mer ge nt S A Es,  
•  Occ urre nce of tr eat me nt -e mer ge nt S A Es,  
•  Treat me nt -e mer ge nt S A Es relate d t o st u d y treat m e nt,  
•  T E A Es wit h fatal o utc o me,  
•  T E A Es relate d t o st u d y tr eat me nt wit h fatal o utc o me,  
A d diti o nall y, s u m maries  will  be  re p orte d  f or T E A Es  a n d  f or  T E A E SIs  b y  e ve nt  o nset, 
i.e., peri - a n d d uri n g P CI. 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 5 9 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
1 0. 3. 5. 2  L a b or at ory d at a 
U nless  n ote d  ot her wise,  s u m maries  a n d  listi n gs  will  i ncl u de  u nsc he d ule d  assess me nts 
re p orte d b y t he ce ntr al la borat or y. 
Descri pti ve  s u m mar y  st atistics  b y  sc he d ul e d  ti me  p oi nt will  be  pr o vi d e d  f or  o bser ve d 
val ues  a n d  a bs ol ute  c ha n ges  fr o m  bas eli ne  i n  b ot h  he mat ol o g y  a n d  bl o o d  c he mistr y 
la b orat or y para meters. 
T he a bs ol ute c ha n ge fr o m baseli ne t o last val ue i n t he treat me nt peri o d f or he mat ol o g y 
a n d bl o o d c he mistr y vari a bles  will be s u m marize d.  
N u m ber ( %) of s u bjects wit h treat me nt -e mer ge nt mar ke d la b orat or y a b n or malities will be 
ta b ulate d a n d all mar k e d la b orat or y a b n or malities will  be liste d. 
1 0. 3. 5. 3  Vit al si g ns  a n d wei g ht  
Eac h s u m mar y a n d listi n g will i ncl u de u nsc h e d ule d asse ss me nts. 
A bs ol ute  c ha n ges  fr o m  baseli ne  t o  last  val ue  o n  st u d y  treat me nt  i n  vital  si g ns  will  be 
s u m marize d. T he a bs ol ute val ues at eac h ti me p oi nt will als o be s u m marize d. 
1 0. 3. 5. 4  S afety m o nit ori n g of m aj or blee di n g a n d de at h 
F or t he  p ur p ose of  s u p p orti n g  t he  I S E C  re vie w,  re g ular  safet y data  re vie w  will  be 
perf or me d.  T his  safet y  m o nit ori n g  will  re p ort a s u m mar y  of  A Es,  f o c usi n g  o n  maj or 
blee di n g e ve nts acc or di n g t o TI MI d efi niti o n, a n d deat h.  
1 0. 4  I nteri m a n al yses 
N o f or mal i nteri m a nal ysis is pla n ne d. 
T his st u d y i n cl u d es r e g ular safet y m o nit ori n g, wit h a re p ort s u b mitte d t o t he I S E C [see 
Secti o n  1 0. 3. 5. 4] . 
1 0. 5  S a m ple si ze  
T he  c o m p utati o n  of  t he  sa m ple  size  was  perf or me d  usi n g  East  6. 0  s oft ware 
( versi o n 6. 4. 0. 1, 3 0 A u g ust 2 0 1 6) fr o m C ytel I n c. 
T he  sa m ple  size  is  base d  o n  t he  st u d y pri mar y o bjecti ve of  assessi n g  I P A   3 0 mi n  after 
A C T -2 4 6 4 7 5  a d mi nistrati o n,  as  assesse d b y t h e pr o p orti o n  of  s u bjects  ac hie vi n g  a 
res p o nse  (i.e., P R U  <  1 0 0  at  3 0  mi n  p ost  st u d y  dr u g  a d mi nistrati o n).  T he  sa m ple  size 
s h o ul d be s ufficie nt t o all o w t he rejectio n at least o ne of t he n ull h y p ot h eses. 
T he st u d y s h o ul d i ncl u d e 2 1 s u bjects e val ua bl e f or t he pri mar y P D e n d p oi nt i n eac h ar m 
c o nsi deri n g: 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 6 0 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
•  a n  o ver all  t w o -si de d  t y p e  I  err or  of  0. 0 5,  a dj uste d  f or  m ulti plicit y  usi n g  t he 
B o nferr o ni  met h o d  f or  eac h  of  t h e  2  n ull h y p ot h eses  (testi n g  eac h  d os e  at  a n  al p ha 
le vel of 0. 0 2 5), 
•  a p o wer of 9 0 %, a n d 
•  t he  f oll o wi n g  ass u m pti o ns  f or  t he  res p o nse  rate  u n der  t he  n ull  a n d  alter nati ve 
h y p ot hes es as re p orte d i n t he ta ble bel o w.  
T a ble 4  
A ss u m ptio ns f or t he res p o nse r ate u n der t he n ull a n d alter n ati ve 
h y p ot heses  a n d s a m ple size  
P r o p orti o n of 
res p o n ders u n der H 0 
P r o p orti o n of 
res p o n ders u n der H 1 
N u m ber of s u bjects  
(t ot al) 
N u m ber of s u bjects  
( per ar m) 
5 0 % 
8 5 %  
4 2 
2 1 
 
1 1  D A T A H A N D LI N G 
1 1. 1  D at a c ollecti o n 
T he  i n vesti gat or/ del e gat e  is  res p o nsi ble  f or  mai ntai ni n g  a de q u ate  a n d  acc urat e  s o urce 
d oc u me nts  a n d  trial  rec or ds  t hat  i ncl u de  all  perti ne nt  o bser vati o ns  o n  eac h  of  t he  site ’s 
trial s u bjects. 
Data  re p orte d  i n  t he eC R F  deri ve d  fr o m  s o urce  d oc u me nts  m ust  be c o nsiste nt  wit h  t he 
s o urce d oc u m e nts. 
eC R F  data  will  be  ca pt ure d  via  electr o nic  d ata  ca pt ure . T h e  i n vesti gat or  a n d  site 
pers o n nel will  be  trai ne d  t o  e nter  a n d  e dit  t he  data  via  a  sec ure  net w or k,  wit h  sec ure 
access feat ures ( user na m e, pass w or d, a n d i de ntifi cati o n – a n el ectr o nic pass w or d s yste m). 
A  c o m plete  electr o ni c  a u dit  trail  will  be  mai ntai ne d.  T he  i n v esti gat or/ dele gate  will 
a p pr o ve  t he  data  (i.e.,  c o nfir m  t he  acc urac y  of  t he  data  rec or d e d)  usi n g  a n  electr o nic 
si g nat ur e (r ef. t o U S  2 1 C F R Part 1 1). 
S u bject scree ni n g a n d ra n d o mizati o n data will be c o m plete d f or all s u bjects (i.e., eli gi ble 
a n d n o n-eli gi ble) t hr o u g h t he eC R F.  
F or  eac h  s u bject  scree n e d  (i.e. ,  w h o pr o vi de d  i nf or me d  c o nse nt ),  re gar dless  of  st u d y 
treat me nt  a d mi nistrati o n,  an  e C R F  m ust  be  c o m plete d  a n d  si g ne d  b y  t he 
i n vesti gat or/ del e gate. T his als o a p plies t o t h ose s u bjects w h o fail t o c o m plete t he st u d y. If 
a s u bject wit h dra ws fr o m t he st u d y, t he reas o n m ust be n ote d o n t he e C R F.  
1 1. 2  M ai nte n a nce of d at a c o nfi de nti alit y 
T he i n vesti gat or/ del e gate  m ust e ns ure t hat data c o nfi de ntialit y is mai ntai n e d. O n eC R Fs 
or  ot her  d o c u me nts  ( e. g.,  d oc u me nts  attac he d  t o  S A E f or ms)  s u b mitte d  t o s p o ns or  a n d 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 6 1 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
a n y C R Os ,  s u bjects  m ust  be  i de ntifie d  o nl y  b y  n u m ber  a n d  n e ver  b y t heir na me  or 
i nitials, date of birt h , h os pital n u m bers, or a n y ot her i de ntifier. T h e i n vesti gat or/ del e gate 
m ust  kee p  a  s u bject  i de ntificati o n  c o d e  list  at  t he  site,  s h o wi n g  t he 
scree ni n g/r a n d o mizati o n  n u m ber,  t he  s u bject’s  na me,  date  of  birt h,  a n d  a d dress  or  a n y 
ot her  l ocall y  acce pt e d  i de ntifi ers. D oc u m e nts i de ntif yi n g t he s u bjects (e. g., si g ne d I C F) 
m ust  n ot  be  se nt  t o 
t he s p o ns or,  a n d  m ust  be  ke pt  i n  strict  c o nfi de nce  b y  t he 
i n vesti gat or/ del e gate. 
1 1. 3  D at a b ase m a n a ge me nt a n d q u alit y c o ntr ol 
eC R Fs will be us e d f or all s u bjects. T he i n v esti gat or (s) will ha v e access t o t he site eC R F 
data u ntil t he data base is l oc ke d. T hereaft er, t he y will ha ve rea d-o nl y access. T he eC R F 
m ust be ke pt c urr e nt t o  reflect s u bject stat us at  a n y ti me p oi nt  d uri n g t h e c o urs e of t he 
st u d y. 
W hile e nteri n g t he dat a, t he i n vest i gat or/ del e gate will be i nsta ntl y alerte d t o data q ueries 
b y  v ali date d  pr o gra m m e d  c hec ks.  A d diti o nal  data  re vie w  will  be  perf or me d  b y 
s p o ns or/ dele gated pers o n nel o n a n o n g oi n g basis t o l o o k f or u ne x pecte d patter ns i n data 
a n d f or st u d y m o nit ori n g. If discr e pa nt data are detecte d, a q uer y s pecif yi n g t he pr o ble m 
a n d re q uesti n g clarificati o n will be iss ue d a n d visi ble t o t he i n vesti gat or/ dele gate via t he 
eC R F. All electr o nic q ueries visi ble i n t he s yste m eit her re q uire a data c orrecti o n ( w he n 
a p plica ble)  a n d  a  res p o nse  fr o m  t he  i n vesti gat or/ dele gate  t o  clarif y  t h e  q uerie d  data 
directl y i n t h e eC R F, or si m pl y a data c orrecti o n i n t he eC R F. T he i n v esti gat or/ d ele gate 
m ust, o n re q uest, pr o vi de t he s p o ns or wit h a n y re q uire d bac k gr o u n d data fr o m t he st u d y 
d oc u me ntati o n  or  cli nical  rec or ds.  T his  is  p arti c ularl y  i m p orta nt  w h e n  err ors  i n  dat a 
tra nscri pti o n are s us p ecte d. I n t he e v e nt of healt h a ut h orit y q ueries, it is als o necessar y t o 
ha ve  access  t o  t he  c o m ple te  st u d y  rec or ds,  pr o vi de d  t hat  s u bject  c o nfi de ntialit y  is 
pr otecte d.  
T his pr ocess will c o nti n ue u ntil data base l oc k. 
La b orat or y  s a m ples  will  be  pr ocess e d  t hr o u g h  a  ce ntral ve n d or a n d  t he  res ults  will  be 
electr o nicall y se nt t o s p o ns or. 
A Es are c o de d acc or d i n g t o t he latest versi o n of Me d D R A use d b y t he s p o ns or. 
After t he data bas e has bee n declare d c o m plete a n d acc urat e, t he data base will be l oc ke d. 
A n y  c ha n ges  t o  t he  d ata base  after  t hat  ti me  m a y  o nl y  be  ma d e  as  descri be d  i n  t he 
a p pr o priate s p o ns or Q u alit y S yste m  d oc u me nts. After data b ase l oc k, t he i n vesti gat or will 
recei v e  t he eC R Fs  of  t h e  s u bjects  of  his/ her  site  (i ncl u di n g  all  data  c ha n ges  ma d e)  o n 
electr o nic me di a.  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 6 2 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
1 2  P R O C E D U R E S A N D G O O D C LI NI C A L P R A C TI C E 
1 2. 1  Et hics a n d G o o d Cli nic al Pr actic e 
S p o ns or / dele gate pers o n nel a n d t he i n vesti gat ors will e ns ure t hat t he st u d y is c o n d ucte d 
i n  f ull  c o m plia nce  wit h t his  pr ot oc ol, I C H-G C P  G ui deli nes,  t he  pri nci ples  of  t he 
“Decl arati o n of H elsi n ki ”, a n d wit h t he l a ws a n d re g ulati o ns of t he c o u ntr y i n w hic h t he 
st u d y is c o n d ucte d.  
1 2. 2  I n de pe n de nt Et hics C o m mittee / I nstit uti o n al Re vie w B o ar d 
T he  i n vesti gat or  will  s u b mit  t his  pr ot oc ol  a n d  a n y  relat e d  d oc u me nt(s)  pr o vi de d  t o  t he 
s u bject  (s uc h  as  t he  I C F)  t o  a n  I E C/I R B.  A p pr o val  fr o m  t he  c o m mittee/ b oar d  m ust  be 
o btai ne d  bef or e  starti n g  t he  st u d y,  a n d  m ust  be  d oc u me nte d  i n  a  date d  letter  t o  t he 
i n vesti gat or,  clearl y  i de ntif yi n g  t he  st u d y,  t he  d oc u me nts  re vi e we d,  a n d  t he  date  of 
a p pr o val. 
M o dificati o ns ma de t o t he pr ot oc ol or t he I C F after recei pt of t h e a p pr o v al m ust als o be 
s u b mitte d  as a me n d me nts  b y  t he  i n vesti gat or  t o  t he  I E C/I R B  i n  acc or da nce  wit h  l ocal 
pr oce d ur es a n d r e g ulati o ns. 
A list of me m bers partici pati n g i n t he I E C/I R B meeti n gs m ust be pr o vi de d, i ncl u di n g t he 
na mes, q ualificati o ns, a n d f u ncti o ns of t h ese me m bers. If t hat is n o t p ossi ble, t he atte m pts 
ma de t o o btai n t his i nf or mati o n al o n g wit h a n e x pla nati o n as t o w h y it ca n n ot be o btai ne d 
or discl ose d m ust be d oc u me nte d i n t he st u d y d oc u me ntati o n.  
If a me m ber of t he st u d y pers o n n el was prese nt d uri n g a n I E C/I R B meeti n g, it m ust  be 
clear t hat t his pers o n di d n ot v ote. 
1 2. 3  I nf or me d c o nse nt 
It is t he res p o nsi bilit y of t he i n vesti gat or/ del e gate t o o btai n i nf or me d c o nse nt acc or di n g 
t o  I C H-G C P  a n d  Decl arati o n  of  Helsi n ki  g ui deli nes  a n d  l ocal  re g ul ati o ns  fr o m  eac h 
i n di vi d ual  partici pati n g i n  t his  st u d y  a n d/ or  le gall y  desi g nate d  re prese ntati ve.  T he 
i n vesti gat or/ del e gate  m ust  e x plai n  t o  s u bjects  t hat  t he y  are  c o m plet el y  free  t o  ref use  t o 
e nter  t he  st u d y,  or  t o  v ol u ntaril y  wit h dra w  fr o m  t he  st u d y  at  a n y  ti me  f or  a n y  r eas o n 
wit h o ut  ha vi n g  t o  p r o vi de  a n y  j ustificati o n.  S pecial  atte nti o n  s hall  be  pai d  t o  t he 
i nf or mati o n nee ds of s pecific s u bject p o p ulati o ns a n d of i n di vi d ual s u bjects, as well as t o 
t he  met h o ds  use d  t o  gi ve  t he  i nf or mati o n.  A de q uate  ti me  s hall  be  gi ve n  f or  t he  s u bject 
a n d/ or  le gall y  d esi g n ate d  re prese nt ati ve  t o  c o nsi der  his  or  her  decisi o n  t o  partici pate  i n 
t he st u d y a n d it s hall be verifie d t hat t he s u bj ect has u n derst o o d t he i nf or mati o n (e. g., b y 
as ki n g t he s u bject t o e x plai n w hat is g oi n g t o ha p p e n). 
T he I C F will be pr o vi d e d i n t he c o u ntr y l o cal la n g ua ge(s). 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 6 3 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
Site  pers o n nel  a ut h orize d  (acc or di n g  t o  l ocal  re g ulati o n)  t o  partici pate  i n  t he  c o nse nt 
pr ocess a n d/ or t o o btai n c o nse nt fr o m t he s u bject a n d/ or le gall y d esi g n ate d re pres e ntati ve 
will be liste d o n t he Del e gati o n of A ut h orit y f or m s u p plie d b y s p o ns or/ d ele gate. A st u d y 
p h ysicia n m ust al w a ys b e i n v ol ve d i n t he c o nse nt pr ocess. 
As m uc h as p ossi ble, t he s u bject a n d/ or le gall y d esi g nat e d re pres e ntati ve a n d a ut h orize d 
site  pers o n nel  liste d  o n  t he  Dele gati o n  of  A ut h orit y  f or m  s u p plie d  b y s p o ns or/ dele gate 
m ust  si g n,  pers o nall y  d ate,  a n d  ti me  (if  t he  first  st u d y -ma n d ate d  pr oce d ure  is  t o  be 
perf or me d  o n  t he  sa m e  da y  i nf or m e d  c o nse nt  is  o btai ne d)  t he  I C F  bef ore  a n y 
st u d y-r elate d  pr o ce d ures  (i.e.,  a n y  pr o ce d ures  re q uire d  b y  t he  pr ot oc ol)  be gi n. As  t h e 
st u d y is recr uiti n g v ul ner a ble s u bjects i n a n e mer ge n c y sit uati o n w h o ma y n ot be a ble t o 
si g n t he c o nse nt f or m at t he start of t he st u d y,  a s pecific pr o cess h as bee n i m ple me nte d 
a n d is descri be d i n S ecti o n 1. 4. 3. 
A c o p y  ( or a sec o n d ori gi nal) of t he si g ne d a n d date d I C F is gi ve n t o t he s u bject a n d/ or 
le gall y  desi g nat e d  re pr ese ntati ve;  t he  ori gi nal  is  file d  i n  t he  site  d oc u me ntati o n.  T he 
i nf or me d  c o nse nt  pr ocess  m ust  be  f ull y  d oc u me nte d  i n  t he  s u bject’s  me dical  rec or ds. 
T his m ust i ncl u de at a mi ni m u m t he st u d y refere n ce, t he s u bject n u m ber, t he date a n d, if 
a p plica ble,  ti me  w he n  t he  s u bject  was  first  i ntr o d uce d  t o  t he  st u d y,  t h e  date  a n d,  if 
a p plica ble,  ti me  of  c o ns e nt,  w h o  partici pate d  i n  t he  c o nse nt  disc ussi o n,  w h o  c o nse nte d 
t he s u bject, a n d a n y a d diti o nal pers o n prese nt d uri n g t he c o nse nt pr ocess (e. g., s u bject’s 
fa mil y me m ber[s]), a n d t he i nf or mati o n t hat a c o p y  of t he si g n e d  I C F was gi ve n t o t he 
s u bject / le gall y d esi g n ate d re prese ntati ve. 
If t he site i nte n ds t o r ecr uit s u bjects w h o are c o nsi dere d v ul nera ble (e. g., s u bject ca n n ot 
rea d or write, d oes n ot s pea k or u n dersta n d t he I C F la n g u a ge), a d diti o nal meas ures m ust 
be i m ple me nte d i n or der t o e ns ure s u bject ’s ri g hts are res pect e d a n d t he c o nse nt o btai ne d 
is le gall y v ali d. T he s p o ns or , t he re g ul at or y a ut h orities (if a p plica ble), a n d t he I E C/I R B 
m ust be i nf or me d pri or t o t he recr uit me nt. T he c o nse nt pr ocess (e. g., i n v ol ve me nt of a n 
i m partial wit ness) m ust be f ull y descri be d, s u b mitte d t o, a n d a p pr o ve d b y t h e I E C/I R B, 
acc or di n g t o pr o ce d ur es a n d bef ore s u bjects are recr uite d. 
1 2. 4  C o m pe ns ati o n t o s u bj ects a n d i n vesti g at ors 
T he  s p o ns or  pr o vi des  i ns ura nce  i n  or d er  t o  i n de m nif y  ( wit h  b ot h  le gal  a n d  fi na ncial 
c o vera ge)  t h e  i n vesti gat or/site  a gai nst  clai ms  arisi n g  fr o m  t he  st u d y,  e x ce pt  f or  clai ms 
t hat arise fr o m mal pr acti ce a n d/ or n e gli ge nce.  
T he c o m pe ns ati o n of t he s u bject i n t he e ve nt of st u d y -relate d i nj uries will c o m pl y wit h 
a p plica ble r e g ulati o ns.  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 6 4 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
St u d y s u bjects will be rei m b urse d f or t he st u d y -rel ate d e x pe nses (e. g., tra vel c osts, meals, 
h otel), a n d ma y be  offer e d fi na ncial c o m pe ns ati o n f or t heir partici p ati o n i n t he st u d y o nl y 
t o t he e xte nt per mitte d b y a p plica ble l ocal re g ulati o ns. 
1 2. 5  Pr ot oc ol a d here nc e/c o m pli a nc e 
T he  i n vesti gat or  m ust  c o n d uct  t he  st u d y  i n  c o m plia nce  wit h  t he  I E C/I R B - a n d/ or  t h e 
re g ulat or y  a ut h orit y-a p pr o ve d  versi o n  of  t he  pr ot oc ol  a n d  m ust  n ot  i m ple me nt  a n y 
de viati o n/c ha n ge  fr o m  t he  pr ot oc ol,  e x ce pt  w he n  de viati o n  is  necessar y  t o  eli mi nate  a n 
i m me diate hazar d t o t he s u bject. 
If  a  pr ot oc ol  d e viati o n  occ urs,  t he  i n vestigat or/ dele gate  will  i nf or m t he  s p o ns or or  its 
re pres e ntati ve i n a ti mel y ma n n er. T h e i n vesti gat or/ dele gate m ust d oc u me nt a n d e x plai n 
a n y  d e viati o n  fr o m  t he  a p pr o ve d  pr ot oc ol.  D e vi ati o ns  c o nsi dere d  t o  be  a  vi olati o n  of 
I C H-G C P  m ust  be  re p orte d  t o  t he  I E C/I R B  a n d  re g ulat or y  a ut h orities  acc or di n g  t o 
s p o ns or or ( o verr uli n g) l ocal re q uire me nts. 
All  pr ot oc ol  de viati o ns  will  be  re p orte d  i n  t he  C S R.  I E Cs/I R Bs  will  be  pr o vi de d  wit h 
listi n gs of pr ot oc ol de viati o ns as per l ocal re q uire me nts. 
1 2. 6  Pr ot oc ol a me n d me nts 
A n y c h a n ge t o t he pr ot o c ol ca n o nl y be ma d e t hr o u g h a writte n pr ot o c ol a me n d me nt. A n 
a me n de d  pr ot oc ol  m ust  be  s u b mitte d  t o  t he  I E C/I R B  a n d  re g ulat or y  a ut h orities, i n 
acc or d a nce wit h l ocal re g ulati o ns a n d pr o ce d ures.  
1 2. 7  Esse nti al d oc u me nts a n d rete nti o n of d oc u me nts 
T he  i n vesti gat or/ d ele gate  m ust  mai ntai n  a de q uate  rec or ds  necess ar y  f or  t he 
rec o nstr ucti o n  a n d  e v al uati o n  of  t he  st u d y.  A  n u m ber  of  attri b utes  are  c o nsi dere d  of 
u ni versal i m p orta nce t o  s o urce data  a n d t he rec or ds  t hat h ol d t h ose data. T hese i ncl u de 
t hat  the  data  a n d  rec or ds  are  acc urat e,  le gi ble,  c o nte m p ora ne o us,  ori gi n al  ( or  certifi e d 
c o p y), attri b uta ble, c o m plete, c o nsiste nt, e n d uri n g, a n d a vaila ble w he n nee de d. 
T hese  rec or ds  are  t o  be  classifie d  i nt o  t w o  differe nt  cate g ori es  of  d oc u m e nts:  I S F  a n d 
s u bjects’ s o urce d oc u me nts. 
T hese rec or ds m ust be k e pt b y t he i n vesti gat or f or as l o n g as is necessar y t o c o m pl y wit h 
t he s p o ns or’s  r e q uire me nts  (i.e.,  as  s pecifie d  i n  t he  cli nical  st u d y  a gree me nt),  a n d 
nati o nal  a n d/ or  i nter nati o nal  re g ulati o ns,  w hic he ver  w o ul d  be  t he  l o n gest  peri o d.  If  t he 
i n vesti gat or ca n n ot g uar a ntee t his arc hi vi n g re q uire me nt at t he  site f or a n y  or all of t he 
d oc u me nts,  s pecial  arr a n ge m e nts,  res pecti n g  t he  data  c o nfi de ntialit y,  m ust  be  ma de 
bet wee n  t he  i n vesti gat or  a n d s p o ns or t o  st ore  t hese d oc u me nts  o utsi de  t he  site,  s o  t hat 
t he y ca n be retrie v e d i n t he e ve nt of a re g ulat or y i ns pecti o n. N o st u d y d o c u me nt s h o ul d 
be  destr o ye d  wit h o ut  pri or  writte n  a p pr o val  fr o m t he s p o ns or.  S h o ul d  t he  i n vesti gat or 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 6 5 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
wis h  t o  assi g n  t he  st u d y  rec or ds  t o  a n ot her  part y,  or  m o ve  t he m  t o  a n ot her  l ocati o n, 
s p o ns or m ust be n otifie d i n a d va nce. 
If t he site uses a n el ectr o nic/c o m p uterize d s yste m t o st ore s u bject me dical rec or ds, it ca n 
be use d f or t he p ur p ose of t he cli nical st u d y if it is vali date d (as per 2 1 C F R Part 1 1 or 
e q ui vale nt sta n dar d) a n d if t he C R A  has bee n pr o vi de d pers o nal a n d restricte d access t o 
st u d y s u bjects o nl y, t o v erif y c o nsiste nc y b et wee n electr o nic  s o urce  d ata  a n d t he eC R F 
d uri n g m o nit ori n g visits.  
If t h e site uses  a n electr o nic/c o m p uterize d s yste m t o st ore s u bject me dical rec or ds b ut it 
c o ul d n ot be c o nfir me d t hat t he s yst e m is vali date d or if t he C R A  c o ul d n ot be pr o vi de d 
access t o t he s yst e m, t he site is re q ueste d t o pri nt t he c o m plet e set of s o urce d ata n ee de d 
f or  verificati o n  b y  t h e C R A .  T he  pri nto uts  m ust  be  n u m bere d,  sta ple d  t o get her  wit h  a 
c o vers heet,  si g ne d  a n d  d ate d  b y  t he  i n v esti gat or/ dele gate  t o  c o nfir m  t hat  t hese  certifie d 
c o pies  ar e  e x act  c o pies wit h  t he  sa me  i nf or mati o n  as  t he  ori gi nal s o urce d ata.  T h e 
pri nt o uts will be c o nsi dere d as t he  offici al cli nical st u d y rec or ds a n d m ust be file d eit her 
wit h t he s u bject’s me dical rec or ds or wit h t he s u bject’ s eC R F.  
I n or d er t o verif y t hat t he pr ocess t he site uses t o pre pare certifie d c o pies is relia ble, t he 
C R A  m ust be a ble t o o bser ve t his pr o cess  a n d c o nfir m t hat t he c o m paris o n of t he s o urce 
d oc u me nts a n d t h e certifie d c o p y di d n ot re v eal i nc o nsiste ncies. T h e C R A  d oes n ot n ee d 
t o verif y t his pr o cess f or all data of all s u bjects b ut at least f or s o me of t h e m (e. g., first 
s u bject;  re g ular  c hec k  d urin g  t h e  st u d y  of  critical  data  li ke  i n cl usi o n/e xcl usi o n  criteria, 
e n d p oi nts f or s o me s u bjects) as per t he s p o ns or’s i nstr ucti o ns. If it was n ot p ossi ble f or 
t he C R A  t o o bser ve t his pr ocess, it w o ul d n ot be  p ossi ble  t o rel y o n t he site’s  certifie d 
c o pies a n d  t her ef or e t he site ca n n ot be selecte d f or t he cli nical st u d y. 
1 2. 8  M o nit ori n g 
Pri or  t o  st u d y  start,  a  site  i nitiati o n  visit  ( SI V)  will  be  perf or me d  aft er  t he  re q uire d 
esse ntial st u d y d oc u me nts are a p pr o v e d b y t he s p o ns or or del e gate. T he st u d y treat me nt 
will b e s hi p pe d t o t he site u p o n a p pr o v al of t he re q uire d esse ntial d oc u me nts. 
T he PI m ust e ns ure t hat all site pers o n nel i n v ol ve d i n t he st u d y are prese nt d uri n g t he SI V 
a n d will de dicate e n o u g h ti me t o it.  
T he  SI V  m ust  be  c o m plete d  bef ore  t he  site  ca n  start  t he  scree ni n g  of  st u d y  s u bjects. 
F oll o wi n g  t he  SI V,  a  c o p y  of  t he  c o m plete d  i nitiati o n  visit  re p ort  a n d  f oll o w -u p  letter 
will be pr o vi de d t o t he PI a n d file d i n t he I S F. 
D uri n g t he st u d y, t he C R A will c o ntact a n d visit t he site re g ul arl y a n d m ust be per mitte d, 
o n re q uest, t o ha ve access t o st u d y facilities  a n d all s o urce d oc u me nts nee de d t o verif y 
a d here n ce  t o  t he  pr ot oc ol  a n d  t he  c o m plete ness,  c o nsiste nc y,  a n d  acc urac y  of  t he  d ata 
bei n g  e nter e d  i n  t he eC R Fs  a n d  ot her  pr ot oc ol -relate d  d o c u me nts. S p o ns or  m o nit ori n g 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 6 6 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
sta n dar ds r e q uire f ull verificati o n t hat i nf or me d  c o nse nt has  bee n pr o vi d e d,  verificati o n 
of  a d her e nce  t o  t he  i n cl usi o n/e x cl usi o n  criteria,  d oc u me ntati o n  of  S A Es,  a n d  t he 
rec or di n g  of  t he  mai n P D ,  safet y,  a n d  t olera bilit y  e n d p oi nts.  A d diti o nal  c hec ks of  t h e 
c o nsiste nc y  of  t he  s o ur ce  d ata  wit h  t he eC R Fs  will  be  p erf or me d  acc or di n g  t o  t he 
st u d y-s pecific  m o nit ori n g  g ui deli nes.  T he  fre q u e nc y  of  t he  m o nit ori n g  visits  will  be 
base d o n s u bject r ec r uit me nt rate a n d critical dat a c ollecti o n ti mes.  
T he PI m ust e ns ure t hat t he eC R F is c o m plete d after s u bject ’s visit, a n d t hat all re q ueste d 
s u bject files (e. g., I C Fs, me dical n otes/c h arts, ot h er d oc u m e ntati o n verif yi n g t h e acti vities 
c o n d ucte d f or t he st u d y) are a v aila ble f or re vi e w b y t he C R A. T he re q uire d site pe rs o n nel 
m ust be a v aila ble d uri n g m o nit ori n g visits a n d all o w a de q u ate ti me t o meet wit h t he C R A 
t o disc uss st u d y-rel ate d iss ues. 
T he i n vesti gat or a gr ees t o c o o perate wit h t he C R A (s) t o e ns ure t hat a n y iss ues detecte d i n 
t he c o urse of t hese m o nit ori n g visits are res ol ve d. If t he s u bject is h os pitalize d or dies i n 
a  h os pital  ot her  t ha n  t h e  st u d y  site,  t he  i n vesti gat or  is  res p o nsi ble  f or  c o ntacti n g  t hat 
h os pital i n or der t o d oc u me nt t he S A E, i n acc or d a nce wit h l ocal re g ulati o ns. 
A cl ose -o ut visit will be perf o r m e d f or a n y i nitiate d site w he n t here  are n o m ore acti ve 
s u bjects  a n d  all  f oll o w-u p  iss ues  ha v e  bee n  res ol ve d.  I f a  site  d oes  n ot  e nr oll  a n y 
s u bjects,  t he  cl ose-o ut  visit  ma y  be  perf or me d  pri or  t o  st u d y  data b ase  cl os ure  at  t he 
discreti o n of s p o ns or. 
1 2. 9  I n vesti g at or Site File 
Eac h site will be pr o vi de d wit h a n I S F at t he latest d uri n g t he SI V. It will c o ntai n  all t he 
esse ntial d oc u me nts t hat are re q uire d t o be u p -t o-date  a n d  file d  at  site  as  per  I C H -G C P 
secti o n 8. 
T he I S F will i ncl u de a t a ble of c o nte nt listi n g t h e esse ntial d oc u me nts. All st u d y-r elate d 
d oc u me ntati o n m ust be mai ntai ne d i n t he I S F. 
I n s o me cas es, e x ce pti o ns ca n be disc uss e d wit h t he C R A  re gar di n g t h e fili n g of t h e st u d y 
d oc u me nts  o utsi de  t he  I S F.  It  s h o ul d  be  cl earl y  d oc u me nte d  w here  eac h  d oc u me nt  is 
file d. T his n ote t o file s h o ul d be prese nt i n t he s pecific ta b of t he d o c u me nt i n t he I S F. 
T he I S F m ust be st ore d i n a sec ure a n d access -restricte d area d uri n g a n d after t he st u d y. It 
m ust be ke pt b y t h e site f or as l o n g as nee de d t o c o m pl y wit h a n y  a p pli ca ble  r ules a n d 
re g ulati o ns,  I C H-G C P,  as  well  as  i nstr ucti o ns  fr o m t he s p o ns or.  If  t h e  site  nee ds  t o 
tra nsfer t he I S F t o a n ot h er l ocati o n a n d/ or if site facilit y ca n n o l o n ger st ore t he I S F, t he 
PI m ust i m me diatel y i nf or m s p o ns or. 
If  t he  PI  will c h a n ge,  or  if  t he  site  will  rel o cate,  t he C R A  m ust  be  n otifie d  as  s o o n  as 
p ossi ble. 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 6 7 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
1 2. 1 0  A u dit  
S p o ns or’ s Q ualit y  Ass ur a nce  re prese ntati ves  ma y  a u dit  t he  i n vesti gat or  site  ( d uri n g  t he 
st u d y  or  after  its  c o m pleti o n).  T he  p ur p ose  of  t his  visit  will  be  t o  deter mi ne  t he 
i n vesti gat or’s a d here nce t o I C H-G C P, t he pr ot oc ol, a n d a p plica ble re g ulati o ns; a d here n ce 
t o s p o ns or’s r e q uire me nts (e. g., sta n d ar d o p erati n g pr oce d ures) will als o b e verifie d. Pri or 
t o i nitiati n g t his a u dit, t h e i n vesti gat or will be c o ntacte d b y s p o ns or/ dele gate t o arra n ge a 
ti me f or t he a u dit. 
T he i n vesti gat or a n d site pers o n nel m ust c o o p erat e wit h t he a u dit or(s) a n d all o w access t o 
all st u d y d oc u me ntati o n ( e. g., s u bj ect rec or ds) a n d facilities. 
1 2. 1 1  I ns pecti o ns 
Healt h A ut h orities a n d/ or I E C/I R B ma y als o c o n d uct a n i ns pecti o n of t his st u d y ( d uri n g 
t he st u d y or after its c o m pleti o n) at t he site. 
S h o ul d  a n  i ns pecti o n  be  a n n o u nce d  b y  a H ealt h A ut h orit y  a n d/ or  I E C/I R B,  t he 
i n vesti gat or  m ust  i m me diatel y  i nf or m t he  s p o ns or ( us uall y  via  t he  C R A)  t hat  s u c h  a 
re q uest has bee n ma de. 
T he i n vesti gat or a n d site pers o n nel m ust c o o perat e wit h i ns pect or(s) a n d all o w access t o 
all st u d y d oc u me ntati o n ( e. g., s u bj ect rec or ds) a n d st u d y facilities. 
1 2. 1 2  Re p orti n g of st u d y res ults a n d p u bli c ati o n 
T he  s p o ns or / dele gate will  p ost  t he  k e y  ele me nts  of  t his  pr ot oc ol  a n d  t he  s u m mar y  of 
res ults  wit hi n  t he  re q uire d  ti meli nes  o n p u blicl y 
accessi ble  data bases  (e. g., 
cli nicaltrials. g o v, E U dat a base), as re q uire d b y la w a n d re g ulati o n. 
St u d y r es ults will be d o c u me nte d i n a C S R t hat will be si g n e d  b y s p o ns or re prese nt ati ves 
a n d t he C o or di nati n g I n v esti gat or ( or PI f or si n gle- ce nter st u dies).  
I n acc or da nce wit h t he G o o d P u blicati o n Practices a n d et hical practice, t he res ults of t he 
st u d y will be s u b mitte d f or p u blicati o n i n a peer-re vie w e d j o ur nal. St u d y res ults ca n be 
s u b mitte d f or prese ntati o n at a c o n gress bef ore s u b missi o n t o a peer-re vi e we d j o ur nal. 
T he  C o or di nati n g  I n vesti gat or  a n d  t he  Steeri n g  C o m mittee,  if  a n y,  will  ha ve  t he 
o p p ort u nit y  t o  re vi e w  t h e  a nal ysis  of  t he  data  a n d  t o  disc uss  t he  i n ter pretati o n  of  t he 
st u d y  r es ults  wit h s p o ns or pers o n n el  pri or  t o  s u b missi o n  t o  a  peer -re vie we d  j o ur n al  or 
prese ntati o n at a c o n gress.  
A ut h ors hi p will be det er mi ne d i n acc or da n ce wit h t he I nter nati o nal C o m mittee of J o ur nal 
E dit ors criteria, a n d b e b ase d o n : 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 6 8 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
•  s u bsta ntial c o ntri b uti o ns t o t he c o nce pti o n or desi g n of t he st u d y, or t he ac q uisiti o n, 
a nal ysis, or i nter pret ati o n of data; a n d 
•  drafti n g of t he p u blicati o n or critical re vie w f or i m p orta nt i ntellect ual c o nte nt; a n d  
•  pr o vi di n g fi nal a p pr o val of t he versi o n t o be p u blis he d; a n d 
•  a gree m e nt  t o  be  acc o u nta ble  f or  all  as p ects  of  t he  w or k  i n  e ns uri n g  t hat  q uesti o ns 
relate d  t o  t he  acc ur ac y  or  i nte grit y  of  a n y  p art  of  t he  w or k  are  a p pr o priatel y 
i n vesti gate d a n d res ol ve d. 
T he  list  of  a ut h ors  of  a n y  p u blicati o n  of  st u d y  res ults  ma y  i ncl u de  re prese ntati ves  of 
s p o ns or a n d will be deter mi ne d b y m ut ual a gree m e nt.  
A n y  st u d y -r elate d p u blicati o n writte n i n de pe n de ntl y b y i n vesti gat ors m ust be s u b mitte d 
t o s p o ns or f or r e vie w at least 3 0 da ys pri or t o s u b missi o n f or p u blicati o n or pres e ntati o n 
at  a  c o n gress.  U p o n  r e vie w, s p o ns or ma y  pr o vi de  c o m me nts,  a n d  ma y  als o  re q uest 
alterati o ns a n d/ or deleti o ns f or t he s ole p ur p ose of pr otecti n g its c o nfi de ntial i nf or mati o n 
a n d/ or pate nt ri g hts. Neit her t he i nstit uti o n n or t he i n vesti gat or s h o ul d per mit p u blicati o n 
d uri n g s uc h a r e vie w peri o d. 
T he s p o ns or’s P olic y o n Scie ntific P u blicati o ns ca n be f o u n d at: 
htt ps:// w w w.i d orsia.c o m/ d oc u me nts/c o m/ p olicies -c harters/ p olic y-s cie ntific-
p u blicati o ns. p df 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 6 9 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
1 3  R E F E R E N C E S 
[ B-1 6. 0 6 4]  I n  vitr o  c o m bi nati o n  of  A C T -2 4 6 4 7 5  wit h  irre versi ble  or  re v ersi ble  P 2 Y 1 2 
a nta g o nists. Researc h re p ort; Acteli o n P har mace uticals Lt d, 1 2 J a n uar y 2 0 1 7. 
[ A C T- 2 4 6 4 7 5 I B] I n v esti gat or’s  Br o c h ure  f or A C T - 2 4 6 4 7 5,  versi o n  3.  I d orsia 
P har mace uticals Lt d, J ul y 2 0 1 7. 
[ Ale x o p o ul os 2 0 1 2]  Ale x o p o ul os  D,  Xa nt h o p o ul o u  I,  G kizas  V,  et  al. Ra n d o mize d 
assess me nt  of  tica gr el or  vers us  pras u grel  a nti plate let  effects  i n  patie nts  wit h 
S T -se g m e nt-ele v ati o n  
m y ocar dial  
i nfarcti o n. 
Circ  
Car di o vas c  
I nter v.  
2 0 1 2; 5( 6): 7 9 7 – 8 0 4. 
[ A mla ni 2 0 1 0] A mla ni S, Na daraja h T, Afzal R, et al. M ortalit y a n d m or bi dit y f oll o wi n g 
a  maj or  blee d  i n  a  r e gistr y  p o p ulati o n  wit h  ac ute  S T  ele v ati o n  m y ocar dial 
i nfarcti o n. J T hr o m b T hr o m b ol ysis 2 0 1 0; 3 0: 4 3 4- 4 0. 
[A nt ma n  2 0 0 0]  A nt ma n  E M,  C o he n  M,  Ber ni n k  PJ,  et  al.  T he  TI MI  ris k  sc ore  f or 
u nsta ble  a n gi na/ n o n -S T  ele vati o n  MI:  A  m et h o d  f or  pr o g n osticati o n  a n d 
t hera pe utic d ecisi o n ma ki n g. J A M A. 2 0 0 0 A u g 1 6; 2 8 4( 7): 8 3 5- 4 2. 
[ Be y g ui 2 0 1 5]  Be y g ui  F,  Castre n  M,  Br u n etti  N D,  et  al. A C C A  st u d y  gr o u p  o n 
pre -h os pital  care.  Pr e -h os pital  ma na ge me nt  of  patie nts  wit h  c hest  pai n  a n d/ or 
d ys p n oea  of  car diac  ori gi n.  A  p ositi o n  pa per  of  t he  Ac ute  Car di o vasc ular  Care 
Ass ociati o n ( A C C A) of t he E S C. E ur Heart J Ac ute Car di o vasc Care. 2 0 1 5 A u g 2 7. 
[ B o nell o 2 0 1 5] B o nell o L, Lai ne M, Ca m oi n -J a u L, N oir ot F, G uie u R, Di g nat-Ge or ge F, 
et al. O ns et of o pti mal P 2 Y 1 2-A D P rece pt or bl oc ka de after tica grel or a n d pras u grel 
i nta ke  i n  N o n-S T  ele vati o n  ac ute  c or o nar y  s y n dr o me.  T hr o m b  Hae m ost.  2 0 1 5; 
1 1 4( 4): 7 0 2- 7. 
[ Ei kel b o o m 2 0 0 6]  Ei kel b o o m  J W,  Me hta  S R,  A na n d  S S,  et  al. A d verse  i m pact  of 
blee di n g  o n  pr o g n osis  i n  patie nts  wit h  ac ute  c or o nar y  s y n dr o mes. Circ ulati o n 
2 0 0 6; 1 1 4: 7 7 4- 8 2. 
[ Ga glia 2 0 1 1]  Ga glia  M A,  T or g us o n  R,  Pa kala  R,  et  al.  C orrelati o n  bet wee n  li g ht  
tra ns missi o n  a g gre g o metr y,  Verif y N o w  P 2 Y 1 2,  a n d  V A S P-P  platelet  reacti vit y 
assa ys  f oll o wi n g  per c uta ne o us  c or o n ar y  i nter ve nti o n.  J  I nter v  Car di ol. 
2 0 1 1; 2 4( 6): 5 2 9- 3 4. 
[ Gar ofal o 2 0 1 2]  Gar ofal o  D,  Gre y  C,  Lee  M,  E x eter  D,  Kerr  AJ.  Pre -h os pital  dela y  i n 
ac ute c or o nar y s y n dr o mes: P R E DI C T C V D- 1 8. N Z Me d J. 2 0 1 2; 1 2 5( 1 3 4 8): 1 2- 2 2. 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 7 0 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
[ G o dsc hal k 2 0 1 7] G o dsc hal k T C, B yr n e R A, A driae nsse ns T, et al. O bser vati o nal st u d y 
of platelet reacti vit y i n p atie nts prese nti n g wit h S T -Se g m e nt ele v ati o n m y ocar dial 
i nfacrti o n d ue t o c or o nar y ste nt t hr o m b osis u n der g oi n g pri mar y c ut a ne o us c or o nar y 
i nter ve nti o n. J A C C Cardi o vasc I nter v.  2 0 1 7; 1 0( 2 4): 2 5 4 8 – 5 6.  
[ Gre m mel 2 0 0 9] Gre m mel T, Stei ner S, Sei di n ger D, K o p pe nstei ner R, Pa nzer S, K o p p 
C W. C o m paris o n  of  met h o ds  t o  e val uate  cl o pi d o grel -me diate d  platel et  i n hi biti o n 
after  p er c uta ne o us  i nter ve nti o n  wit h  ste nt  i m pla ntati o n.  T hr o m b  Hae m ost.  2 0 0 9 
Fe b; 1 0 1( 2): 3 3 3- 9. 
[ Gre m mel 2 0 1 5] Gre m mel T, K o p pe nstei ner R, Pa nzer S. C o m paris o n of A g gre g o metr y 
wit h Fl o w C yt o metr y f or t he Assess me nt of A g o nists´ -I n d u ce d Platelet Reacti vit y 
i n Patie nts o n D ual A nti platelet T hera p y. P L o S O n e. 2 0 1 5 J u n 9; 1 0( 6):e 0 1 2 9 6 6 6. 
[ G ur bel 2 0 0 3] G ur bel P A, Bli de n K P, Hiatt B L, O ’C o n n or C M. Cl o pi d o grel f or c or o nar y 
ste nti n g: r es p o nse v aria bilit y, dr u g resista nce, a n d t he effect of pretreat me nt platelet 
reacti vit y. Circ ulati o n 2 0 0 3; 1 0 7: 2 9 0 8- 1 3. 
[I ba nez 2 0 1 7] I ba n ez  B,  J a mes  S,  A ge w all  S, et  al. 2 0 1 7 E S C  G ui d eli nes  f or  t he 
ma na ge me nt of ac ut e m y ocar dial i nfarcti o n i n p atie nts prese nti n g wit h S T -se g me nt 
ele vati o n:  T he T as k  F or ce  f or  t he  ma n a ge me nt  of  ac ut e  m y ocar dial  i nfarcti o n  i n 
patie nts  prese nti n g  wit h  S T -se gme nt  ele v ati o n  of  t he  E ur o pea n  S ociet y  of 
Car di ol o g y ( E S C).  E ur H eart J . 2 0 1 8; 3 9( 2): 1 1 9- 7 7.  
[J u d ge 2 0 1 6] J u d ge H M, B uc kla n d RJ, J a k u b o ws ki J A, St ore y R F. Ca n grel or i n hi bits t he 
bi n di n g  of  acti ve  m eta b olites  of  cl o pi d o grel  a n d  pras u grel  t o  P 2 Y 1 2 rece pt ors  i n 
vitr o. Platelets 2 0 1 6; 2 7( 3): 1 9 1 – 5. 
[ Ke n gr e x al®  S m P C]  Ke n gre x al ®  s u m mar y  of  pr o d uct  c haract eristics. 
E ur o pea n 
Me dici nes A ge nc y Ke n gre x al
®  pr o d uct i nf or mati o n. [accesse d o n 1 3  Marc h  2 0 1 8]. 
A vaila ble fr o m:    
htt p:// w w w.e ma.e ur o pa. e u/ d ocs/e n _ G B/ d oc u m e nt _li brar y/ E P A R _-
_ Pr o d uct _I nf or mati o n/ h u ma n/ 0 0 3 7 7 3/ W C 5 0 0 1 8 8 0 9 8. p df 
[ Matetz k y 2 0 0 4]  Matetz k y  S,  S he n k ma n  B,  G u etta  V,  et  al.  Cl o pi d o grel  resista nce  is 
ass ociate d wit h i ncrease d ris k of rec urre nt at her ot hr o m b otic e ve nts i n pati e nts wit h 
ac ute m y ocar dial i nfarcti o n. Circ ulati o n 2 0 0 4; 1 0 9: 3 1 7 1- 5. 
[ Me hra n 2 0 1 1] Me hra n R, Ra o S V, B hatt D L, et al. Sta n dar dize d blee di n g defi niti o ns f or 
car di o vas c ular  cli nical  trials:  a  c o nse ns us  re p ort  fr o m  t he  blee di n g  aca de mic 
researc h c o ns orti u m. Circ ulati o n 2 0 1 1; 1 2 3: 2 7 3 6 – 4 7. 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 7 1 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
[ M o ntalesc ot 2 0 1 4]  M o ntalesc ot  G,  v a n ‘t  H of  A,  La p ost olle  F, et  al.  Pre h os pital 
Tica grel or  i n  S T -Se g me nt  Ele vati o n  M y ocar dial  I nfarcti o n.  N  E n gl  J  Me d 
2 0 1 4; 3 7 1: 1 0 1 6 – 2 7. 
[ M orr o w 2 0 0 0]  M orr o w  D A,  A nt ma n  E M,  C harles w ort h  A,  et  al .  TI MI  ris k  sc ore  f or 
S T -Ele vati o n  MI:  A  c o n ve nie nt  be dsi de  cli nical  sc ore  f or  ris k  assess me nt  at 
prese ntati o n: A n I n Ti me II S u bst u d y. Circ ulati o n 2 0 0 0; 1 0 2( 1 7): 2 0 3 1 – 7. 
[ Na bel 2 0 1 2] Na bel E G, Bra u n wal d E. A tal e of c or o nar y art er y disease a n d m y o car dial 
i nfarcti o n. N E n gl J Me d. 2 0 1 2; 3 6 6: 5 4 – 6 3. 
[ Par o di 2 0 1 3]  Par o di  G,  Vale nti  R,  Bella n di  B,  et  al. C o m paris o n  of  pras u grel  a n d 
tica grel or  l o a di n g  d oses  i n  S T-se g me nt  ele v ati o n  m y ocar dial  i nfarcti o n  patie nts: 
R A PI D ( Ra pi d A cti vit y of Platelet I n hi bit or Dr u gs) pri mar y P CI st u d y. J A m C oll 
Car di ol. 2 0 1 3; 6 1( 1 5): 1 6 0 1 – 6. 
[ Re y 2 0 1 7]  Re y  M,  Kr a m ber g  M,  Hess  P,  et  al.  T he  re versi ble  P 2 Y 1 2  a nta g o nist 
A C T -2 4 6 4 7 5  ca uses  si g nifica ntl y  less  bl o o d  l oss  t ha n  tica grel or  at  e q ui vale nt 
a ntit hr o m b otic efficac y i n rat. P har mac ol Res Pers pect. 2 0 1 7; 5( 5) e P u blis he d. 
[ R olli ni 2 0 1 6] R olli ni F, Fra nc hi F, A n gi olill o DJ. S witc hi n g  P 2 Y 1 2 -rece pt or i n hi bit ors 
i n patie nts wit h c or o nar y arter y disease. N at Re v Car di ol.  2 0 1 6 1 3( 1): 1 1 – 2 7. 
[ Sa v o nitt o 2 0 1 7]  Sa v o nitt o  S,  De  L u ca  G,  G ol dstei n  P,  et  al.  A ntit hr o m b otic  t hera p y 
bef ore,  d uri n g  a n d  aft er  e mer ge n c y  a n gi o plast y  f or  S T  ele vati o n  m y ocar dial 
i nfarcti o n. E ur H eart J Ac ute Car di o vasc C are 2 0 1 7; 6( 2): 1 7 3 – 9 0. 
[ Sc h nei der 2 0 1 4]  Sc h nei der  DJ,  A gar w al  Z,  Seec hera n  N,  Keati n g  F K,  G o g o  P. 
P har mac o d y na mic  eff ects  d uri n g  t he  tra nsiti o n  bet wee n  ca n grel or  a n d  ti ca grel or. 
J A C C Car di o vasc I nter v. 2 0 1 4; 7( 4): 4 3 5 – 4 2. 
[ Stei n h u bl 2 0 0 8] Stei n h u bl  S R,  O h  JJ,  Oestreic h  J H,  Ferraris  S,  C har ni g o  R,  A kers  W S. 
Tra nsiti o ni n g p atie nts fr o m ca n grel or t o cl o pi d o grel: p har mac o d y na mic e vi de nce of 
a c o m petiti ve eff ect. T hr o m b Res.  2 0 0 8; 1 2 1( 4): 5 2 7 – 3 4.  
[ T u bar o 2 0 1 1]  T u bar o  M,  Da nc hi n  N,  G ol dst ei n  P,  et  al.  Pre -h os pit al  treat me nt  of 
S T E MI patie nts. A scie ntific state me nt of t he W or ki n g Gr o u p Ac ute Car diac Care 
of t he E ur o pea n S ociet y of Car di ol o g y. Ac ute Car d Care 2 0 1 1; 1 3( 2): 5 6 – 6 7. 
[ Val gi mi gli 2 0 1 8] Val gi mi gli M., B u e n o H., B yr ne R., et al. 2 0 1 7 E S C f o c use d u p dat e o n 
d ual a nti platelet t hera p y i n c or o nar y arter y diseas e de vel o pe d i n c olla b orati o n wit h 
E A C T S: T he Tas k F orce f or d ual a nti plate let t hera p y i n c or o nar y arter y disease of 
t he  E ur o pea n  S ociet y  of  Car di ol o g y  ( E S C)  a n d  of  t he  E ur o p ea n  Ass oci ati o n  f or 
Car di o - T h oracic S ur ger y ( E A C T S). E ur. Heart J. 2 0 1 8; 3 9( 3): 2 1 3 – 6 0.  

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 7 2 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
[ Vare n h orst 2 0 0 9]  Var e n h orst  C,  J a mes  S,  Erli n ge  D,  et  al.  Ass ess me nt  of  P 2 Y( 1 2) 
i n hi biti o n wit h t he p oi nt- of-care d e vice Verif y N o w P 2 Y 1 2 i n patie nts treate d wit h 
pras u grel  or  cl o pi d o gr el  c oa d mi nistere d  wit h  as piri n.  A m  Heart  J.  2 0 0 9; 
1 5 7( 3): 5 6 2.e 1- 9. 
[ Wa n g 2 0 1 0] Wa n g L, Wa n g X, C he n F. Cl o pi d o grel resista nce is ass ociate d wit h l o n g -
ter m  t hr o m b otic  e ve nts  i n  patie nts  i m pla nte d  wit h  dr u g-el uti n g  ste nts. Dr u gs  i n 
R & D 2 0 1 0; 1 0: 2 1 9 – 2 4. 
[ Wils o n 2 0 1 7] Wils o n SJ, Ne w b y D E, Da ws o n D, et al. D urati o n of a nti platelet t hera p y 
i n ac ute c or o n ar y s y n dr o me. Heart 2 0 1 7; 1 0 3: 5 7 3 – 5 8 0. 
[ Wi vi ott 2 0 0 7]  Wi vi ott  S D,  Bra u n w al d  E,  Mc Ca be  C H,  et  al. Pras u grel  vers us 
cl o pi d o gr el  i n  patie nts  wit h  ac ut e  c or o nar y  s y n dr o mes.  N  E n gl  J  Me d 
2 0 0 7; 3 5 7: 2 0 0 1 – 1 5. 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 7 3 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
1 4  A P P E N DI C E S 
A p pe n di x 1 
TI MI r is k sc ore 
TI MI ris k sc or e will b e calc ulate d f or eac h p atie nt b y site a n d t he calc ulate d sc ore will b e 
rec or d e d i n t he eC R F. Calc ulati o n will be acc or di n g t o t he f oll o wi n g c h aracteristics:  
T he TI MI ris k sc ore f or S T E MI  [M orr o w  2 0 0 0] (t otal sc ore bet w ee n 0 a n d 1 4): 
•  A ge  
–  < 6 5: 0 p oi nts 
–  6 5 – 7 4: 2 p oi nts 
–  ≥ 7 5: 3 p oi nts 
•  At least o ne of t he f oll o wi n g Me dical Hist or y: 1 p oi nt  
–  Dia betes m ellit us 
–  H y p erte nsi o n  
–  A n gi na p ect oris 
•  S yst olic bl o o d press ure at scree ni n g < 1 0 0 m m H g: 3 p oi nts 
•  P ulse rate at scr ee ni n g > 1 0 0 b p m: 2 p oi nts 
•  Killi p class at scree ni n g II –I V: 2 p oi nts 
•  Wei g ht at scr ee ni n g < 6 7 k g: 1 p oi nt 
•  Ti me fr o m s y m pt o m o ns et t o first d ose of fi bri n ol ytic > 4 h o urs: 1 p oi nt 
•  A nteri or MI or l eft b u n dle bra nc h bl o c k: 1 p oi nt 
T he TI MI ris k sc ore f or N S T E MI  [A nt ma n  2 0 0 0] (t otal sc ore bet wee n 0 a n d 7): 
•  A ge ≥ 6 5: 1 p oi nt 
•  At least 3 ris k fact ors f or C A D: 1 p oi nt 
–  Fa mil y hist or y of C A D  
–  H y p erte nsi o n  
–  H y p erc h olest er ole mia  
–  Dia betes  
–  C urre nt s m o ker 
•  K n o w n C or o nar y Ste n osis ≥ 5 0 %: 1 p oi nt 
•  Prese nce of ≥ 0. 5 m m S T se g me nt d e viati o n o n a d missi o n E C G: 1 p oi nt 
•  Se vere a n gi n a ( ≥ 2 e pis o des i n last 2 4 hrs): 1 p oi nt 
•  At least o ne ele v ate d ser u m car diac m ar kers: 1 p oi nt  
–  Creati ne ki nase M B  
–  Car diac -s p ecific tr o p o ni n le vel 
•  Use of as piri n i n t he last 7 da ys: 1 p oi nt 
 

A C T -2 4 6 4 7 5  
C or o n ar y arter y dise ase  
Pr ot oc ol I D-0 7 6 A 2 0 2  
Versi o n 2 
1 1 A pril 2 0 1 8 , pa ge 7 4 /7 4  
C o nfi de nti al  
E u dr a C T 2 0 1 8 -0 0 0 7 6 5 -3 6  
D oc N o D -1 8. 0 7 8  
 
A p pe n di x 2 
Killi p cl ass f or MIs  
Killi p cl assific ati o n will be assesse d as:  
•  Killi p class I: A bse n ce of rales o ver t h e l u n g fiel ds a n d a bse nce of a n S 3  
•  Killi p class II: Rales o v er  5 0 % or less of t he l u n g fiel ds or t he prese n ce of a n S 3 
•  Killi p class III: R ales o ver m ore t ha n 5 0 % of t he l u n g fiel ds 
•  Killi p  class  I V:  Car di o ge nic  s h oc k:  si g ns  i ncl u de  h y p ote nsi o n  (s yst olic  press ure  of 
9 0 m m H g  or  less)  a n d  e vi de nce  of  peri p heral  vas oc o nstricti o n  s uc h  as  oli g uria, 
c ya n osis a n d dia p h or esis.