Clinical trial NCT03487445
Conditions: Acute Myocardial Infarction
Sponsor: Viatris Innovation GmbH
Start date: 2018-07-10; Completion date: 2018-11-10
Enrollment: 48 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The goal of this study is to find out how fast a drug called selatogrel (ACT-246475) can prevent platelets from binding together. This study will also help to find out more about the safety of this new drug. The drug selatogrel (ACT-246475) will be used in 2 different doses (8 mg or 16 mg) and will be administered in the thigh.

Detailed description:
This study is planned in patients presenting with Acute Myocardial Infarction (AMI) scheduled for an invasive strategy. Platelet activation and thrombus formation play a pivotal role in the pathophysiology of acute coronary syndrome. Early platelet inhibition has been shown to reduce the risk of recurrent events after a myocardial infarction.

The screening period starts when the participant provides informed consent and ends with participant's randomization. Eligible participants had an acute myocardial infarction (AMI; ST-segment elevation myocardial infarction \[STEMI\] or non-ST-elevation myocardial infarction \[NSTEMI\]), a life-threatening condition, and will therefore fulfill the ICH-GCP definition of vulnerable subjects ("persons in emergency situations"). Accordingly, a specific process for obtaining consent in compliance with local regulations and approved by the independent ethics committee will be implemented.

The study will be performed during a participant's hospital stay related to the qualifying AMI.

Standard treatment of AMI is allowed including anticoagulants. Ticagrelor will be the only oral P2Y12 receptor antagonist allowed to be initiated during the study and its administration will be possible only after selatogrel administration. Use of fibrinolytics or GPIIb/IIIa inhibitors will be prohibited unless required for bail-out. All other standard-of-care treatments for AMI will be allowed without restriction.

The treatment period starts with the participant's randomization and ends after the end-of-study assessments, approximately 48 hours after the administration of a single study treatment dose.

Arms: arm 1: Selatogrel (ACT-246475) is given as a single subcutaneous dose of 8 mg administered in a volume of 0.8 mL. Administration will be performed at the investigational site by qualified personnel. arm 2: Selatogrel (ACT-246475) is given as a single subcutaneous dose of 16 mg administered in a volume of 0.8 mL. Administration will be performed at the investigational site by qualified personnel.
Interventions: intervention 1: Selatogrel 8 mg intervention 2: Selatogrel 16 mg
Intervention descriptions: intervention 1: Selatogrel is a reversible P2Y12 receptor antagonist for subcutaneous administration. It is supplied in sealed glass vials at a strength of 20 mg. The vials with ACT-246475A (hydrochloride salt of ACT-246475) will be reconstituted with 1 mL of water and further diluted with 1 mL sodium chloride (NaCl) 0.9%. intervention 2: Selatogrel is a reversible P2Y12 receptor antagonist for subcutaneous administration. It is supplied in sealed glass vials at a strength of 20 mg. The vials with ACT-246475A (hydrochloride salt of ACT-246475) will be reconstituted with 1 mL of water for injection.

Protocol documents:
Prot_000.pdf: 
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. 
 

SAP_001.pdf: 
Statistical Analysis Plan:  
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 
 




A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 2 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
T A B L E O F C O N T E N T S 
1  
I N T R O D U C TI O N ......................................................................................................... 8 
2  
S T U D Y D E SI G N A N D F L O W .................................................................................... 8  
2. 1  
St u d y d esi g n  ................................................................................................... 8 
2. 2  
St u d y visit a n d ass ess me nt sc he d ule .............................................................. 9  
2. 3  
O ver vie w of a nal ysis peri o ds ......................................................................... 9  
3  
O BJ E C TI V E S  ............................................................................................................... 9 
3. 1  
Pri mar y o bjecti ve(s)  ....................................................................................... 9 
3. 2  
Sec o n dar y o bjecti ves ...................................................................................... 9  
3. 3  
Ot her o bjecti ves  .............................................................................................. 9 
4  
A N A L Y SI S S E T S  ....................................................................................................... 1 0 
4. 1  
Defi niti o ns of a nal ysis sets  ........................................................................... 1 0 
4. 1. 1  
Scree ne d a nal ysis set  ........................................................................ 1 0 
4. 1. 2  
Ra n d o mi ze d a nal ysis set  ................................................................... 1 0 
4. 1. 3  
F ull a nal ysis set  ................................................................................. 1 0 
4. 1. 4  
M o difie d F ull a nal ysis set ................................................................. 1 0  
4. 1. 5  
Per -pr ot oc ol a n al ysis set  ................................................................... 1 0 
4. 1. 6  
Safet y a nal ysis set  ............................................................................. 1 0 
4. 1. 7  
P har mac o ki netic a n al ysis set  ............................................................ 1 1 
4. 2  
Usa ge of t he a nal ysis sets  ............................................................................. 1 1 
5  
S T U D Y S U BJ E C T S, V A RI A B L E S  A N D A N A L Y S E S  ........................................... 1 1 
5. 1  
S u bject dis p ositi o n ........................................................................................ 1 2  
5. 1. 1  
Scree ni n g fail ures  ............................................................................. 1 2 
5. 1. 2  
St u d y c o m pleti o n/ disc o nti n uati o n  .................................................... 1 2 
5. 1. 3  
St u d y treat me nt c o m pleti o n/ disc o nti n uati o n  ................................... 1 2 
5. 2  
Pr ot oc ol de viati o ns ....................................................................................... 1 2  
5. 3  
I n cl usi o n i n / e x cl usi o n fr o m a nal ysis sets ................................................... 1 2 
5. 3. 1  
S u bject dis p ositi o n ............................................................................ 1 2  
5. 4  
S u bject c haracteristics  .................................................................................. 1 3 
5. 4. 1  
De m o gra p hics ................................................................................... 1 3  
5. 4. 2  
Baseli ne disease c haracteristics  ........................................................ 1 3 
5. 4. 3  
Ot her baseli ne c haracteristics  ........................................................... 1 3 
5. 4. 4  
Pre vi o us a n d c o nc o mita nt me dical hist or y ....................................... 1 3  
5. 4. 5  
Q ualif yi n g ac ute m y ocar dial i nfarct c h aracteristics  ......................... 1 3 
5. 4. 6  
Pre vi o us a n d c o nc o mita nt t hera pies ................................................. 1 4  


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 3 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
5. 4. 7  
Ot her s u bject c h aracteristics  ............................................................. 1 6 
5. 5  
St u d y treat me nt e x p os ure a n d c o m plia nce ................................................... 1 6  
5. 5. 1  
E x p os ure ........................................................................................... 1 6  
5. 5. 2  
C o m plia nce wit h st u d y treat me nt  ..................................................... 1 6 
6  
E F FI C A C Y V A RI A B L E S A N D A N A L Y S E S  ........................................................... 1 6 
6. 1  
O ver vie w  ...................................................................................................... 1 6 
6. 2  
Pri mar y e n d p oi nt a nal ysis ............................................................................ 1 6  
6. 3  
Ke y sec o n d ar y e n d p oi nt a nal ysis ................................................................. 1 6  
6. 4  
Ot her efficac y e n d p oi nt a nal ysis .................................................................. 1 6  
6. 5  
A nal ysis of q u alit y of life varia bles  .............................................................. 1 7 
6. 6  
A nal ysis of p h ar mac oec o n o mic varia bles  .................................................... 1 7 
6. 7  
A nal ysis of e pi de mi ol o gi cal meas ures a n d ris k - b e nefit e val uati o ns ............ 1 7 
6. 8  
A nal ysis of p h ar mac o d y na mic varia bles  ...................................................... 1 7 
6. 8. 1  
Pri mar y p h ar mac o d y n a mic e n d p oi nt  ................................................ 1 7 
6. 8. 1. 1  
Varia ble  .................................................................................. 1 7 
6. 8. 1. 2  
A nal ysis  .................................................................................. 1 8 
6. 8. 1. 3  
S u p p orti ve/se nsiti vit y a n al yses  .............................................. 1 9 
6. 8. 1. 4  
S u b gr o u p a n al ys es .................................................................. 1 9  
6. 8. 2  
Ot her p har m ac o d y na mic e n d p oi nts a nal ysis .................................... 2 0  
6. 8. 2. 1  
Varia bles  ................................................................................. 2 0 
6. 8. 2. 2  
A nal ys es  ................................................................................. 2 0 
6. 8. 2. 3  
S u p p orti ve/se nsiti vit y a n al yses .............................................. 2 0  
6. 8. 2. 4  
S u b gr o u p a n al ys es .................................................................. 2 1  
6. 8. 3  
Ha n dli n g of missi n g data  .................................................................. 2 1 
6. 9  
A nal ysis of p h ar mac o ki neti c varia bles  ......................................................... 2 1 
7  
S A F E T Y V A RI A B L E S A N D  A N A L Y S E S  ............................................................... 2 1 
7. 1  
O ver vie w of saf et y a nal yses i ncl u di n g s u b gr o u p a nal yses .......................... 2 1  
7. 2  
A d verse e ve nts  .............................................................................................. 2 1 
7. 2. 1  
Varia bles  ........................................................................................... 2 2 
7. 2. 1. 1  
All a d verse e ve nts  .................................................................. 2 2 
7. 2. 1. 2  
Treat me nt -e mer ge nt a d v erse e v e nts  ....................................... 2 2 
7. 2. 1. 3  
Treat me nt -e mer ge nt a d v erse e v e nts relat e d t o st u d y 
treat me nt ................................................................................. 2 2 
7. 2. 1. 4  
Treat me nt -e mer ge nt a d v erse e v e nts b y i nte nsit y  ................... 2 2 
7. 2. 1. 5  
Seri o us a d verse e ve nts  ............................................................ 2 2 
7. 2. 1. 6  
A d verse e ve nts lea di n g t o deat h  ............................................. 2 2 
7. 2. 1. 7  
A d verse e ve nts lea di n g t o st u d y treat me nt 
disc o nti n uati o n ....................................................................... 2 2  
7. 2. 1. 8  
Ot her a d ver se e v e nt cat e g ories ............................................... 2 2 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 4 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
7. 2. 2  
A nal ysis  ............................................................................................ 2 3 
7. 2. 3  
A nal ys es f or k e y st u d y d ata discl os ure t o re g ulat or y a ut h orities ..... 2 3  
7. 3  
Deat h  ............................................................................................................. 2 3 
7. 4  
La b orat or y tests  ............................................................................................ 2 3 
7. 4. 1  
Meas ure me nts  ................................................................................... 2 3 
7. 4. 2  
A nal ysis  ............................................................................................ 2 4 
7. 5  
Electr ocar di o gra p h y a nal ysis  ........................................................................ 2 4 
7. 6  
Vital si g ns a n d b o d y w ei g ht ......................................................................... 2 4  
7. 6. 1  
Bl o o d press ure a n d p ulse rate a n al ysis ............................................. 2 4  
7. 6. 2  
B o d y wei g ht, a n d ot her vital si g n a nal yses ....................................... 2 4  
7. 7  
Ot her saf et y v aria bl es a n d a nal ys es  .............................................................. 2 5 
8  
G E N E R A L S T A TI S TI C A L M E T H O D O L O G Y  ........................................................ 2 5 
8. 1  
Ge ner al r ules f or data prese ntati o ns ............................................................. 2 5 
8. 1. 1  
Treat me nt gr o u ps  .............................................................................. 2 5 
8. 1. 2  
Descri pti ve statistics  ......................................................................... 2 5 
8. 2  
Efficac y a nal ys es  .......................................................................................... 2 6 
9  
I N T E RI M A N A L Y S E S .............................................................................................. 2 6 
1 0  G E N E R A L D E FI NI TI O N S A N D D E RI V A TI O N S  ................................................... 2 6 
1 0. 1  
A nal ysis peri o ds a n d visit wi n d o ws ............................................................. 2 6  
1 0. 2  
Dates, ti mes a n d da ys  ................................................................................... 2 6 
1 0. 2. 1  
Defi niti o n of st u d y start  .................................................................... 2 6 
1 0. 2. 2  
Baseli ne  ............................................................................................. 2 6 
1 0. 2. 3  
P ost- baseli ne assess me nt  .................................................................. 2 6 
1 0. 2. 4  
Treat me nt start dat e/ti me  .................................................................. 2 6 
1 0. 2. 5  
Defi niti o n of e n d of st u d y treat me nt ................................................. 2 6  
1 0. 2. 6  
Defi niti o n of E n d- of- St u d y  ............................................................... 2 7 
1 0. 2. 7  
Defi niti o n of scree ni n g fail ure  .......................................................... 2 7 
1 0. 2. 8  
Defi niti o n of pre mat ure st u d y disc o nti n uati o n ................................. 2 7  
1 0. 3  
Defi niti o n of reas o n f or s cree ni n g fail ure ..................................................... 2 7  
1 0. 4  
C o n ve nti o n f or de m o gra p h y dat a c o nsi dere d f or a nal ysis w he n 
m ulti ple val ues re p orte d  ............................................................................... 2 7 
1 0. 5  
C o di n g dicti o naries ....................................................................................... 2 7  
1 0. 6  
Me dical hist or y a n d c urre nt (st u d y c o nc o mita nt) me dical c o n diti o ns ......... 2 8  
1 0. 7  
Pre vi o us a n d c o nc o mita nt me dicati o n .......................................................... 2 8  
1 1  C H A N G E S O R C L A RI FI C A TI O N S T O A N A L Y S E S P L A N N E D I N T H E 
S T U D Y P R O T O C O L  ................................................................................................. 2 8 
1 1. 1  
C ha n ges t o t he a nal yses pla n ne d i n t he st u d y pr ot oc ol ................................ 2 8  


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 5 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
1 1. 1. 1  
C ha n ge i n s e nsiti vit y a nal ysis ........................................................... 2 8  
1 1. 1. 2  
St u d y dr u g e x p os ure ......................................................................... 2 9  
1 1. 2  
C ha n ges i n t he c o n d uct of t he st u d y / dat a c ollecti o n .................................. 2 9  
1 1. 3  
Clarificati o ns c o ncer ni n g e n d p oi nt defi niti o ns a n d relate d varia bles or 
statistical met h o ds ......................................................................................... 2 9 
1 1. 4  
A d diti o nal a nal ys es as c o m pare d t o t he st u d y pr ot oc ol ............................... 2 9  
1 2  LI S T O F T A B L E S, LI S T I N G S A N D FI G U R E S ....................................................... 2 9 
1 3  A P P E N DI C E S  ............................................................................................................. 3 0 
 
 
LI S T O F T A B L E S 
 
Ta ble 1  
St u d y d o c u me nts .............................................................................................. 8  
Ta ble 2  
A nal ysis dat asets  usa ge  .................................................................................. 1 1 
Ta ble 3  
Oral P 2 Y 1 2 rece pt or a nta g o nists ..................................................................... 1 5 
Ta ble 4  
Defi niti o n of e x cl usi o ns fr o m a nal ysis sets ................................................... 3 7  
Ta ble 5  
Ha n dli n g of missi n g/i nc o m plete date a n d ti me .............................................. 4 0 
 
 
LI S T O F FI G U R E S 
 
Fi g ure  1 
St u d y d esi g n  ..................................................................................................... 9 
 
LI S T O F A P P E N DI C E S 
 
A p pe n di x A  
Pr ot oc ol s y n o psis ............................................................................. 3 0  
A p pe n di x B  
Pr ot oc ol de viati o n list ...................................................................... 3 7  
A p pe n di x C  
Defi niti o ns of mar ke d a b n or malities  ............................................... 3 9 
A p pe n di x D  
Ha n dli n g of missi n g or i nc o m plete date a n d/ or ti me  ....................... 4 0 
A p pe n di x E  
D oc u me nt hist or y ............................................................................. 4 1  
 
 
 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 6 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
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 E   
A d verse e ve nt  
A E SI   
A d verse e ve nt of s pecial i nterest  
A MI   
Ac ute m y ocar dial i nfarcti o n  
A T C   
A nat o mical T hera pe utic C he mical  
B MI   
B o d y mass i n de x  
CI   
C o n fi de nce i nter v al 
C ma x   
Ma xi m u m plas ma c o nce ntrati o n  
C R F   
Case Re p ort F or m  
D A P T   
D ual a nti platelet t hera p y  
E O S   
E n d -of -St u d y  
F A S   
F ull a nal ysis set  
I N N  
I nter nati o nal N o n pr o prietar y Na me 
I P A  
I n hi biti o n of platelet a g gre gati o n 
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  
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 
P D   
P har mac o d y na mic(s)  
P K   
P har mac o ki netic(s)  
P P S   
Per -pr ot oc ol set  
P R U   
P 2 Y 1 2 reacti o n u nits 
P T   
Preferre d Ter m  
R N D   
Ra n d o miz e d a nal ysis set  
s.c.  
S u bc uta ne o us (l y) 
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 C R   
Scree ne d a nal ysis set  
S D   
Sta n dar d de viati o n  
S M Q   
Sta n dar dise d Me dical Di cti o nar y f or Re g ul at or y Acti vities  
Q uer y  


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 7 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
S O C   
S yste m or ga n class  
S T E MI   
S T -se g m e nt ele vati o n m y o car dial i nfarcti o n 
T E A E   
Treat me nt -e mer ge nt a d v erse e v e nt  
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  
W H O   
W orl d Healt h Or ga nizati o n  
 
 




A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 9 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
Fi g ure  1 
St u d y desi g n  
  
 
2. 2  St u d y visit a n d assess me nt sc he d ule 
Please ref er t o t he pr ot o c ol secti o n 7. 
2. 3  O ver vie w of a n al ysis peri o ds 
T he st u d y h as 2 peri o ds: 
1.  Scree ni n g peri o d : fr o m si g nat ure of i nf or m e d c o nse nt u p t o ti me of ra n d o mizati o n. 
2.  Tre at me nt  peri o d :  fr o m  ra n d o mizati o n  a n d  u p  t o  4 8  h o urs  ( 2  da ys)  after  t he 
a d mi nistrati o n of t he si n gle d ose of A C T- 2 4 6 4 7 5 [see Secti o n 1 0. 1 f or m ore details]. 
3  
O B J E C TI V E S 
3. 1  Pri m ar y o bjecti ve(s) 
T he  pri mar y  o bj ecti ve  of  t he  st u d y  is  t o  assess  t he  i n hi biti o n  of 
a de n osi ne 
di p h os p hate- i n d uce d  platelet  a g gre gati o n 3 0  mi n utes after a  si n gle  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 ula nts). 
3. 2  Sec o n d ar y o bjecti ves 
N ot a p plica ble.  
3. 3  Ot her o bje cti ves 
T he ot her o bjecti ves of t his st u d y are: 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 1 0 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
•  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. 
4  
A N A L Y SI S S E T S 
4. 1  Defi niti o ns of a n al ysis sets 
U nless n ot rele va nt, or ot her wise s pecifie d, s u m mar y statistics will b e pr o vi de d b y  st u d y 
treat me nt gr o u p (i.e., d ose le vel) a n d c o m bi ni n g all s u bjects [as descri be d i n Secti o n 8. 1. 1] . 
4. 1. 1  Scree ne d a n al ysis set  
T he Scree ne d a nal ysis set ( S C R) i ncl u des all s u bjects w h o pr o vi de d i nf or me d c o nse nt a n d 
recei v e d a s u bject i de ntificati o n n u m ber. 
4. 1. 2  R a n d o mize d a n al ysis set 
T he Ra n d o mize d a nal ysis set ( R N D) i ncl u des all s u bjects fr o m t he S C R  w h o ha ve b ee n 
assi g ne d t o a st u d y tr eat me nt (i.e. , ha ve a ra n d o mizati o n n u m ber). 
4. 1. 3  F ull a n al ysis set  
T he  F ull  a n al ysis  set  ( F A S)  i ncl u des  all  s u bj ects  fr o m  t he  R N D  w h o  ha ve  bee n 
a d mi nistere d t he st u d y tr eat me nt.  
S u bjects  will  be  e val uat e d  acc or di n g  t o  t he  act u al  st u d y  treat me nt  d ose  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 st u d y treat me nt d ose. 
4. 1. 4  M o difie d F ull a n al ysis set  
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 2 Y 1 2 reacti o n u nits (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.  
4. 1. 5  Per - pr ot o c ol a n al ysis set 
T he Per -pr ot o c ol set ( P P S ) c o m prises all s u bjects fr o m t he m 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 de q uate esti mati o n of t he st u d y 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 st u d y treat me nt, a v aila bilit y of ke y 
e n d p oi nt meas ure m e n ts 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 st u d y treat me nt effect. 
T he  f ull  list  of  criteria  ( pr ot oc ol  de viati o ns  a n d  ot her  reas o ns  f or  e x cl usi o n)  will  be 
esta blis he d pri or t o cli nical data base l o c k a n d is detaile d i n  A p pe n di x B.  
4. 1. 6  S af et y a n al ysis set  
T he Safet y a nal ysis set ( S A F) i ncl u des all s u bjects fr o m t he S C R w h o recei ve d t he st u d y 
treat me nt (i.e., A C T - 2 4 6 4 7 5 8 or 1 6 m g). 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 1 1 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
S u bjects  will  be  e val uat e d  acc or di n g  t o  t he  act u al st u d y treat me nt d ose 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 st u d y treat me nt d ose. 
4. 1. 7  P h ar m a c o ki netic a n al ysis set 
T he P K a nal ysis set ( P K set) i ncl u des all s u bjects fr o m t he S A F  w h o ha ve at least o ne P K 
sa m ple  (i.e., at least  o ne plas ma A C T - 2 4 6 4 7 5 c o nce ntrati o n  meas ure me nt ) after 
a d mi nistrati o n of st u d y tr eat me nt.  
S u bjects i n t he P K set will be e val uate d acc or di n g t o t he act ual st u d y treat me nt d ose t he y 
recei v e d, w hic h ma y diff er fr o m t he ra n d o ml y assi g ne d st u d y treat me nt. 
4. 2  Us a ge of t he a n al ysis sets 
T he a nal ysis sets us e d f or statistical a nal yses of s pecific v aria bles are s h o w n i n  Ta ble 2 . 
S u bject data listi n gs ar e t o be pre pare d usi n g t he S C R , u nless ot her wise s pecifie d. 
T a ble 2  
A n al ysis d at asets us a ge 
 
A n al ysis sets  
A n al yses  
S C R  
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  
 
 
 
 
 
 
Pr ot oc ol de viati o ns, A nal ysis sets  
X  
 
 
 
 
 
 
De m o gra p hics c haracteristics  
 
x  
X  
 
( x) 
 
 
Me dical hist or y a n d c urre nt me dical 
c o n diti o ns  
 
 
X 
 
  
  
 
Pre vi o us a n d c o nc o mita nt me di cati o ns  
 
 
X  
 
 
 
 
St u d y treat me nt e x p os ure  
 
 
 
 
 
X  
 
Mai n ( pri mar y) P D e n d p oi nts  
 
 
 
X  
( x) 
 
 
Ot her P D e n d p oi nts  
 
 
X  
 
 
 
 
Safet y a n d t olera bilit y e n d p oi nts  
 
 
 
 
 
X  
 
P K e n d p oi nts  
 
 
 
 
 
 
X  
N ote: X: mai n a n al ysis, x: a n al ysis t o b e p erf or me d u nless e xact sa me set as f or mai n a n al ysis, ( x): se nsiti vit y a nal ysis 
t o b e c o n d u cte d o nl y if > 1 0 % differ e n ce of set size wit h set use d f or mai n a n al ysis. F A S,  F ull a n al ysis set; 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 har mac o ki n etic(s);  P P S, P er -pr ot oc ol  set ; R N D,  
Ra n d o mize d a n al ysis s et; S A F, Safet y a n al ysis s et ; S C R, Scree n e d a n al ysis s et . 
 
5  
S T U D Y S U B J E C T S , V A RI A B L E S A N D A N A L Y S E S 
F or  cate g orical  v aria ble s,  t he  i nci de n ce  of  s u bj ects  b y  cate g or y  will  b e  s u m marize d 
(fre q u e nc y c o u nts a n d perce nta ges), whil e f or c o nti n u o us varia ble s, s u m maries will use t he 
f oll o wi n g  descri pti ve  statistics,  u nless  state d  ot her wise:  arit h metic  mea n, sta n dar d 
de viati o n ( S D ), mi ni m u m, 1st q uartile, me dia n, 3r d q uartile, a n d ma xi m u m.  


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 1 2 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
5. 1  S u bject dis p ositi o n 
5. 1. 1  Scree ni n g f ail ures  
T he sta n dar d d efi niti o n of scree ni n g fail ure, as des cri be d i n S ecti o n 1 0. 2. 7,  will be  use d. 
S u m mar y  of  s u bjects  b y  stat us ; scree ne d,  ra n d o mize d,  a n d  treate d, b y  c o u ntr y  a n d b y 
ce nter will be pr o vi de d. 
Reas o n f or scree ni n g  fail ure will  be liste d.  
5. 1. 2  St u d y c o m pleti o n/ disc o nti n u ati o n  
T he defi niti o n of st u d y pre mat ure disc o nti n uati o n as d escri be d i n S ecti o n 1 0. 2. 8 will b e  
use d.  
S u m mar y  of  s u bjects  b y  st u d y  c o m pleti o n  stat us  (c o m pleti n g  st u d y  vs  pre mat ure 
disc o nti n uati o n ), a n d distri b uti o n b y reas o n f or pre mat ure st u d y  disc o nti n uati o n will be 
pr o vi de d. 
5. 1. 3  St u d y tre at me nt c o m pleti o n/ disc o nti n u ati o n  
N ot a p plica ble.  
5. 2  Pr ot oc ol de vi ati o ns 
S u bject s wit h at least o ne pr ot oc ol de viati o n, t he o verall a n d i m p orta nt de viati o ns will be 
s u m marize d f or scree ni n g, a n d treat me nt peri o d [see Secti o n 2. 3] .  
S u bjects will be c o u nte d o nce i n eac h s u m mar y, i. e. , if a s u bject has m ore t ha n 1 pr ot oc ol 
de viati o n f or a gi ve n cat e g or y/s u b-cat e g or y/ descri pti o n, t he s u bject will be c o u nte d o nl y 
o nce i n s u m maries f or t his cate g or y/s u b- cate g or y/ descri pti o n. 
S u bjects’  p r ot oc ol  d e viati o ns  will  be  liste d.  T his  listi n g  will  i ncl u d e  all  d e viati o n 
descri pti o ns, i de ntifiers a n d cate g ories. S u bjects wit h o ut a n y pr ot oc ol de viati o ns are n ot 
i ncl u de d i n t his listi n g. 
5. 3  I ncl usi o n i n / e x cl usi o n fr o m an al ysis sets 
5. 3. 1  S u bject dis p ositi o n  
A s u m mar y ta bl e will pr ese nt a n o ver vie w (fre q u e nc y a n d perce nt a ge ) of t he recr uit me nt 
f or eac h c o u ntr y a n d site, b y d ose gr o u p a n d o verall. 
T he s u bject s’ dis p ositi o n (fre q u e nc y a n d p erce nta ge ) will be s u m marize d b y d ose gr o u p  
a n d o verall f or t he defi ne d a nal ysis s ets.  
T he reas o n f or e x cl usi o n of s u bjects fr o m eac h a n al ysis set will be liste d. 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 1 3 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
5. 4  S u bject c h ar acteristics 
5. 4. 1  De m o gr a p hics 
T he f oll o wi n g d e m o gra p hic  c haract eristics are c ollecte d i n t he st u d y Case Re p ort F or m 
(C R F ):  
•  A ge ( years)  
•  Se x cate g or y: M al e a n d Fe m ale  
•  Race gr o u p: Bl ack or Afric a n A meric a n, A m eric a n I n di a n or Al ask a n ative, N ative 
H a w aii a n or ot her P acific isl a n der, Asi a n, W hite, Ot her, N ot a p plic a ble 
•  Et h nic cate g or y: His p a ni c or L ati n o, N ot His p a nic or L ati n o, a n d U nk n o w n  
•  B o d y wei g ht ( k g) at scr ee ni n g  
•  Hei g ht ( c m) at scree ni n g  
•  C o u ntr y  
I n a d diti o n, t he f oll o wi n g varia bles at b aseli ne are deri ve d:  
•  A ge gr o u p: < 1 8 t o < 6 5, ≥ 6 5 t o < 8 5, a n d ≥ 8 5 ye ars  
•  A ge gr o u p: < 5 5  a n d ≥ 5 5 ye ars 
•  B o d y mass i n de x ( B MI ; k g/ m 2)  
•  B MI cate g or y: < 2 5, ≥ 2 5 t o < 3 0, a n d ≥ 3 0. 0 k g/ m 2. 
B MI at scree ni n g will be c o m p ute d usi n g t he f oll o wi n g f or m ula: B MI ( k g/ m2) = wei g ht / 
hei g ht 2, wit h we i g ht e x presse d i n kil og ra ms, a n d h ei g ht i n meters. 
5. 4. 2  B aseli ne dise ase c h ar acteristics  
N ot a p plica ble.  
5. 4. 3  Ot her b aseli ne c h ar acteristics  
N ot a p plica ble.  
5. 4. 4  Pre vi o us a n d c o nc o mit a nt m e dic al hist or y  
F or t h e t w o cate g ories, pr e vi o us a n d c o nc o mita nt me d ical hist or y, t he i nci d e nce of s u bjects 
wit h t he e ve nt will be s u m marize d (fre q u e nc y c o u nts a n d perce nta ges) b y s yste m or ga n 
class ( S O C) a n d/ or pr eferre d ter m ( P T). 
5. 4. 5  Q u alif yi n g ac ute m y oc a r di al i nf arct i o n c h ar acteristics  
I n a d diti o n t o me dical hist or y, t he c haracteristics of t he q ualif yi n g A MI , are als o c ollecte d , 
w hic h  i ncl u des: 
•  O nset date a n d ti me of A MI s y m pt o ms  
•  Dia g n osis : S T E MI ( all, t hr o m b ol ysis i n m y ocar di al i nfarcti o n [TI MI ] sc ore < 3, TI MI 
sc ore ≥ 3), N S T E MI (all, TI MI sc ore < 5, TI MI sc ore ≥ 5) 
•  T hr o m b ol ysis i n m y o c ar dial i nfarcti o n  ris k sc ore: ra n ge fr o m 0 t o 1 4 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 1 4 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
•  Killi p class : I, II, III, I V 
•  S ur gical, t hera p e utic or dia g n ostic pr o ce d ures perf or me d : 
–  Perc uta ne o us c or o nar y i nter ve nti o n 
–  C or o nar y a n gi o gr a p h y 
–  Bar e metal ste nt i nserti o n  
–  Dr u g el uti n g ste nt i nserti o n  
–  Bi ores or b a ble vas c ular s caff ol d ste nt i nserti o n  
–  Ot her  
F or t he  cate g ori cal  vari a bles,  t he n u m ber of  s u bjects  b y  cate g or y  will  be  s u m marize d 
(fre q u e nc y c o u nts a n d perce nta ges). 
T he  ti me (i n  h o urs) si nce  o nset  of A MI  s y m pt o ms  t o  st u d y  dr u g  i nj ecti o n will  be 
s u m marize d usi n g descri pti ve statistics. 
Als o, t he fre q ue nc y of di a betes mellit us , h y p erte nsi o n, d ysli pi de mia,  a n d chr o nic ki d ne y 
disease at bas eli ne will be s u m marize d (c o u nts a n d perce nt a ges).  
Dia betes mellit us is a n y me dical h ist or y M e d D R A P T  bel o n gi n g t o Me d D R A Hi g h L e vel 
T er m  “Di a betes  m ellit us  (i ncl.  s u bty pes)”,  e xisti n g  pri or  t o, a n d  o n g oi n g  o n  da y  of , 
i nf or me d c o nse nt si g nat ure. 
C hr o nic ki d ne y diseas e is a n y me dical hist or y o bser vati o n wit h  Me d D R A P T  bel o n gi n g t o 
t he Sta n dar dise d M e d D R A Q uer y  ( S M Q) “C hr o nic ki d ney dise ase ”, e xisti n g pri or t o, a n d 
o n g oi n g o n da y of, i nf or me d c o nse nt si g n at ure.  
H y p erte nsi o n is defi ne d as a n y m e dical hist or y o bser vati o n wit h Me d D R A P T bel o n gi n g 
t o  t he  S M Q  “Hy perte nsi o n ” of  narr o w  ter ms ,  e xisti n g  pri or  t o,  a n d  o n g oi n g  o n  da y  of, 
i nf or me d c o nse nt si g nat ure.  
H y p erte nsi o n is defi ne d as a n y m e dical hist or y o bser vati o n wit h Me d D R A P T bel o n gi n g 
t o t he S M Q “Dysli pi d ae mi a ” of narr o w ter ms, e xisti n g pri or t o, a n d o n g oi n g o n da y of, 
i nf or me d c o nse nt si g nat ure.  
Pre -d osi n g tr o p o ni n T will als o be s u m marize d b y usi n g descri pti ve statistics, b y treat me nt 
gr o u p. 
5. 4. 6  Pre vi o us a n d c o nc o mit a nt t her a pies  
I n t his st u d y, o nl y m e dicati o ns are t o be c ollecte d. 
T he  ha n dli n g  of  missi n g  or  i nc o m plete  date/ti me  of  pre vi o us/c o nc o mita nt  t hera pies  is 
descri be d i n  A p p e n di x D. 
T he f oll o wi n g cate g ories [see Secti o n  1 0. 7 f or defi niti o n] will be c o nsi dere d f or a nal ysis: 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 1 5 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
•  Pre vi o us me dicati o ns,  
•  St u d y c o nc o mita nt me dicati o ns,  
•  St u d y- treat me nt c o nc o mita nt me dicati o ns at baseli ne,  
•  St u d y- treat me nt c o nc o mita nt me dicati o ns.  
Oral  P 2 Y 1 2 rece pt or  a nt a g o nists at  baseli ne i ncl u de  a n y st u d y-treat me nt  c o nc o mita nt 
me dicati o ns at baseli ne  i ncl u de d i n t he f oll o wi n g list s h o w n i n Ta ble 3,  a n d a d mi nistere d 
o n t he da y of a d mi nistrati o n of st u d y me dicati o n : 
T a ble 3  
Or al P 2 Y 1 2 rece pt or a nt a g o nists 
A T C c o de  
I n gre die nt na me  
B 0 1 A C 0 4   
cl o pi d o gr el   
B 0 1 A C 0 5   
ticl o pi di ne  
B 0 1 A C 2 2   
pras u grel   
B 0 1 A C 2 4   
tica grel or  
A T C, A n at o mic al T h era p e utic C h e mical.  
F or st u d y-tr eat me nt  c o n c o mita nt me dicati o ns  at  baseli ne, st u d y-treat me nt  c o nc o mita nt 
me dicati o ns, a n d o ral P 2 Y1 2 rece pt or a nta g o nists at baseli ne cat e g ories, t h e i nci de nce of 
s u bjects  wit h  a  me dicati o n  will  be  s u m marize d  (fre q u e nc y  c ou nts  a n d  p erce nt a ges)  b y 
A nat o mical T her a pe utic C he mical  (A T C ) c o d e c orres p o n di n g t o t he I N N. 
All pre vi o us/c o nc o mita nt me dicati o ns will be liste d.  
T he n u m ber  a n d  pr o p orti o n  of  s u bjects  wit h  s uc h  a st u d y-treat me nt c o nc o mita nt 
me dicati o n  at  baseli ne  will  be s u m marize d  (fre q ue nc y  c o u nts  a n d  p erce nta ges)  b y  t h e 
f oll o wi n g cate g ories :  
1.  N o as piri n/acet ylsalic ylic aci d n or P 2 Y 1 2 rece pt or a nta g o nist 
St u dy-tre at me nt c o n c o mit a nt me dic ati o ns  at b aseli ne  ( base d o n i n gre die nt list) 
D o n ot i ncl u de  as piri n/acet yls alic yli c aci d  or  car basalate o r  cl o pi d o grel o r  pras u grel 
or  tica grel or or  ticl o pi di ne 
2.  As piri n/acet ylsalic ylic aci d m o n ot hera p y 
St u dy-tre at me nt c o n c o mit a nt me dic ati o ns  at b aseli ne  ( base d o n i n gre die nt list) 
I n cl u de as piri n/acet yls alic ylic aci d  or car b asalate, a n d  d o n ot i ncl u de cl o pi d o grel or  
pras u grel or  tica gr el or or ticl o pi di ne. 
3.  P 2 Y 1 2 rece pt or a nta g o nist m o n ot hera p y at least o ne, a n d f or eac h dr u g: cl o pi d o grel, 
pras u grel, a n d tica gr el or . 
St u dy-tre at me nt c o n c o mit a nt me dic ati o ns  at b aseli ne  ( base d o n i n gre die nt list) 
D o n ot i ncl u de  as piri n/acet ylsalic ylic aci d  or car b asalate, a n d  i ncl u de cl o pi d o grel o r  
pras u grel or  tica gr el or or ticl o pi di ne. 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 1 6 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
4.  D ual a nti platelet t her a p y ( D A P T ): as piri n/acet yls alic ylic aci d a n d cl o pi d o grel. 
St u dy-tre at me nt c o n c o mit a nt me dic ati o ns  at b ase li ne ( base d o n i n gre die nt list) 
I n cl u de as piri n/acet ylsalic ylic aci d  or car b asalate, a n d  cl o pi d o grel. 
5.  D A P T: as piri n/acet ylsali c ylic aci d a n d tica grel or. 
St u dy tre at me nt c o nc o mit a nt me dic ati o ns  at b aseli ne  ( base d o n i n gre die nt list) 
I n cl u de as piri n/acet ylsa lic ylic aci d or car b asalate, a n d  tica grel or. 
6.  D A P T: as piri n/acet ylsali c ylic aci d a n d pras u grel . 
St u dy tre at me nt c o nc o mit a nt me dic ati o ns  at b aseli ne  ( base d o n i n gre die nt list) 
I n cl u de as piri n/acet ylsalic ylic aci d  or car b asalate, a n d  pras u grel . 
7.  D A P T: a n y c o m b i nati o n. 
St u dy tre at me nt c o nc o mit a nt me dic ati o ns  at b aseli ne  ( base d o n i n gre die nt list) 
I n cl u de as piri n/acet ylsali c ylic  aci d   or car b asalate , a n d   cl o pi d o grel or  pras u grel o r  
tica grel or o r  ticl o pi di ne. 
5. 4. 7  Ot her s u bject c h ar a ct eristics  
N ot a p plica ble.  
5. 5  St u d y tre at me nt e x p os ure a n d c o m pli a nce  
5. 5. 1  E x p os ure 
T he  n u m ber  a n d  per ce nta ge  of  s u bjects  b y  st u d y  dr u g  a d mi nis trati o n  stat us will  be 
pr o vi de d.  
5. 5. 2  C o m pli a nce wit h st u d y tre at me nt  
N ot a p plica ble.  
6  
E F FI C A C Y V A RI A B L E S A N D A N A L Y S E S 
6. 1  O ver vie w 
N ot a p plica ble.  
6. 2  Pri m ar y e n d p oi nt a n al ysis 
N ot a p plica ble.  
6. 3  Ke y sec o n d ar y e n d p oi nt a n al ysis 
N ot a p plica ble.  
6. 4  Ot her effic a c y e n d p oi nt a n al ysis 
N ot a p plica ble.  


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 1 7 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
6. 5  A n al ysis of q u alit y of life v ari a bles 
N ot a p plica ble.  
6. 6  A n al ysis of p h a r m ac o ec o n o mic v ari a bles 
N ot a p plica ble.  
6. 7  A n al ysis of e pi d e mi ol o gic al me as ures a n d ris k- be nefit e v al u ati o ns 
N ot a p plica ble.  
6. 8  A n al ysis of p h a r m ac o d y n a mic v ari a bl es 
F or  cate g orical  varia ble s,  t he  i nci de nce  of  s u bjects  b y  cate g or y  will  be  s u m marize d  b y 
usi n g fre q ue n c y c o u nts, perce nt a ges a n d t he c orres p o n di n g 9 5 % c o nfi de n ce i nt er v al ( CI) 
w he n rele v a nt .  
C o nti n u o us  varia bles  will  be  s u m marize d  usi n g:  arit h metic  mea n,  S D,  mi ni m u m, 
1 st q uartile, me dia n, 3r d q uartile, ma xi m u m, a n d 9 5 % CI  of t he mea n  w he n rele va nt . 
6. 8. 1  Pri m ar y p h ar m ac o d y n a mic e n d p oi nt  
T he st u d y is d esi g n e d t o de m o nstrat e t hat a si n gle i njecti o n of 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  s u bjects  t o  ac hie ve  a  cli nicall y  m ea ni n gf ul  le vel  of 
i n hi biti o n of platelet a g gre gati o n (I P A), i.e., P R U < 1 0 0 at 3 0 mi n utes  after  st u d y dr u g 
i njecti o n.  
6. 8. 1. 1  V ari a ble 
T he p ri mar y p har mac o d y na mic ( P D ) e n d p oi nt is t he P D res p o nse t hat is d efi ne d f or eac h 
s u bject as a P R U < 1 0 0 at 3 0 mi n after st u d y dr u g i njecti o n, as meas ure d vi a Verif y N o w® .  
T he pri mar y P D v aria ble (P R U 3 0 m) is t he platel et reacti vit y as meas ure d b y Verif y N o w ®  at 
3 0 mi n after st u d y dr u g i njecti o n [ see t he ta ble of assess me nts i n t he pr ot oc ol, t a ble 2] .  
T he a nal ysis vari a ble of t he P D res p o nse is defi ne d as f oll o ws f or a gi v e n s u bject: 
I F P R U3 0 m < 1 0 0  
T H E N P D res p o nse = Y E S  
E L S E P D res p o nse = N O 
P R U t i me is base d o n pla n ne d ti me p oi nt a n d n ot o n t he act ual c ollecti o n ti me. 
S u p p orti ve pri m a r y P D e n d p oi nt  
T he  f oll o wi n g  e n d p oi nt  is  n ot  descri be d  i n  t he  pr ot oc ol  a n d  h as  b ee n  a d de d.  T he  mai n 
p ur p ose is t o ass ess t he effect of t he t w o st u d y treat me nt d oses , w h e n rela xi n g t he ti me of 
a P R U < 1 0 0 , i.e., c o nsi deri n g as a res p o nse a P R U < 1 0 0 at 1 5, 3 0 or 6 0 mi n. p ost i njecti o n . 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 1 8 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
T his e n d p oi nt is defi ne d as per t he f oll o wi n g al g orit h m a n d will descri be t he s u bject's P D 
res p o nse wit hi n  t he 1st h o ur: 
I F mi ni m u m of ( P R U 1 5 m, P R U 3 0 m, P R U6 0 m) < 1 0 0  
T H E N P D res p o nse wit hi n 1 st h o ur = Y E S  
E L S E P D res p o nse wit hi n 1 st h o ur = N O  
W here P R U
1 5 m, P R U3 0 m, a n d P R U6 0 m refer t o P R U meas ure d b y V erif y N o w®  at 1 5, 3 0, 
a n d 6 0 mi n utes after st u d y dr u g a d mi nistrati o n.  
P R U t i me is base d o n pla n ned ti me p oi nt a n d n ot o n t he act ual c ollecti o n ti me.  
6. 8. 1. 2  A n alysis  
T he  a nal yses  descri b e d  i n  t his  secti o n c o nsi der t he pri mar y e n d p oi nt, i.e., P D res p o nse. 
Se nsiti vit y a n al ysis of t h e P D e n d p oi nts will be  descri be d i n Secti o n 6. 8. 1. 3. 
U nless state d ot her wise, all a nal ys es will be c o n d ucte d o n t he m F A S.  
H y 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).  
T o ac hie ve t his o bjecti ve, t he testi n g strate g y will be t o test t he st u d y treat me nt effect ( usi n g 
t he pr o p orti o n p  of res p o n ders, i.e., ac hie vi n g P R U < 1 0 0 at 3 0 mi n utes p ost -i njecti o n) f or 
eac h of t h e t w o d oses, c o nsi deri n g t he f oll o wi n g h y p ot heses: 
H 0 H D: p H D  ≤ 5 0 % vs H1 H D: pH D  ≥ 8 5 % 
H 0 L D: p L 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 her 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 h eses 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. 0 2 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 err o ni met h o d. 
M ai n a n al ysis 
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 be base d o n t he st u d y treat me nt 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 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 1 9 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
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 pr ot oc ol 
secti o n 1 0. 3. 3. 1]. 
T he st u d y will be declare d p ositi ve f or t he pri mar y o bjecti ve, if at l east 1 o ut of t he 2 n ull 
h y p ot hes es is reject e d at 0. 0 2 5 t y pe 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. 
A s u m mar y of res p o ns e, 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. 
6. 8. 1. 3  S u p p ortive/se nsitivity a n aly ses 
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 be pr o vi de d c o nsi deri n g t he a vaila ble P D assess m e nt ti me p oi nts 
( baseli ne, 1 5, 3 0, a n d 6 0 mi n p ost d ose).  
A mi x e d m o del t o assess treat me nt effect at 3 0 mi n. fr o m start of treat me nt i njecti o n o n 
platelet reacti vit y as meas ure d b y Verif y N o w ® , i. e., P R U val ue, will be p erf or me d usi n g 
s u bject as a ra n d o m fact or, a n d treat me nt ( 8 m g, a n d 1 6 m g), a ge (c o nti n u o us), se x ( male, 
fe male), a n d ti me fr o m o nset of sy m pt o ms t o st u d y treat me nt a d mi nistrati o n (c o nti n u o us, 
h o urs), as fi x e d fact ors.  
Ass u mi n g  r ele va nt  n u m ber  of  s u bjects (i.e.,  ≥  1 0  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 nter acti o n eff ect of S T E MI/ N S T E MI wit h st u d y treat me nt d ose i n t he pri mar y 
e n d p oi nt a nal ysis. L o gistic re gressi o n a nal ysis of t he P D res p o nse will be p erf or me d usi n g 
A C T -2 4 6 4 7 5  d ose  ( 8  m g vs 1 6  m g),  S T -se g m e nt  ele vati o n  ( S T E MI  vs  N S T E MI),  a ge 
(c o nti n u o us), a n d ge n d er ( male  vs fe mal e) as c o variates. 
T he  sa me  a nal ysis  as  descri be d  i n t he mai n  a nal ysis  secti o n  will  be  perf or me d  o n  t he 
a d diti o nal P D res p o nse wit hi n t he 1 st h o ur e n d p oi nt usi n g t he F A S. 
T he  mai n  a nal ysis ,  o n  t he  P D  res p o nse,  a n d  P D  res p o nse  wit hi n t he 1 st  h o ur, will  be 
re peat e d o n t he P P S if t he P P S is at least 1 0 % s maller t ha n t he mF A S.  
6. 8. 1. 4  S u b gr o u p a n alyses 
T he pr ot oc ol d oes n ot pla n a n y a nal ysis b y s u b gr o u p, h o we ver t he st u d y treat me nt effect 
acr oss t he f oll o wi n g s u b gr o u ps  will be e x pl ore d b y re peatin g t he mai n a nal ysis o n pri mar y 
P D e n d p oi nt, ass u mi n g t here are e n o u g h s u bjects, i.e., ≥ 1 0 s u bjects b y s u b gr o u p.  
•  A ge: < 5 5 vs ≥ 5 5 years 
•  B MI : < 2 5. 0 vs ( ≥ 2 5. 0 a n d < 3 0. 0) vs ≥ 3 0. 0 k g/ m2 
•  Se x : male vs fe male 
•  Dia betes mellit us at baseli ne: yes vs n o  


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 2 0 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
•  C hr o nic ki d ne y disease: yes vs n o 
P T s t o  c o nsi der  f or  i de ntificati o n  of  s u bjects  wit h/ wit h o ut  dia betes  mellit us,  or  c hr o nic 
ki d ne y disease, are des cri be d i n S ecti o n 5. 4. 4.  
6. 8. 2  Ot her p h ar m a c o d y n a mic e n d p oi nts a n al ysis 
U nless state d ot her wise, all a nal ys es will be c o n d ucte d o n t he F A S.  
6. 8. 2. 1  V ari a bles 
E n d p oi nts  
O t her P D e n d p oi nt s ar e t he f oll o wi n g: 
•  P D pr ofile over ti me  b ase d o n a bs ol ute P R U v al ues at 1 5, 3 0 a n d 6 0 mi n utes p ost d ose, 
•  P R U 6 0 m st at us: P R U stat us ( val ue < 1 0 0) at t he 6 0 mi n utes p ost d ose ti me p oi nt.    
V ari a bles  
T he P D pr ofile over ti me  varia ble will be  base d o n act ual  P R U val ues re p orte d at 1 5, 3 0 
a n d 6 0 mi n utes after st u d y dr u g i njecti o n . 
T he P R U 6 0 m varia bl e is t he act ual P 2 Y 1 2 reacti o n u nit val ue as re p orte d b y Verif y N o w ® , at 
6 0 mi n after st u d y dr u g i njecti o n .  
6. 8. 2. 2  A n alyses  
S u m mar y  st atistics  will  be  pr o vi de d  f or t he P D e n d p oi nt  varia ble  P R U 6 0 m  st at us,  a n d 
i n di vi d ual data will b e liste d. It will b e a nal yze d si milarl y t o t h e pri mar y P D e n d p oi nt i n 
S ecti o n 6. 8. 1. 2 , a n d will use t he sa me fact ors. 
A  l o n git u di nal  a nal ysis  of  t he st u d y treat me nt  effect,  o n P D  pr ofile  over  ti me  will  be 
perf or me d usi n g a mi x e d m o del wit h P R U as t he de pe n de nt v aria ble, s u bject as a ra n d o m 
fact or, a n d st u d y treat me nt (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), P R U le vel at 
baseli ne , ti me  fr o m  o ns et  of  s y m pt o ms  t o  st u d y  treat me nt  a d mi nistrati o n  (c o nti n u o us, 
h o urs), a ge (c o nti n u o us), se x ( male, fe male), a n d assess me nt ti me ( 1 5, 3 0 a n d 6 0  mi n utes) 
as fi x e d fact ors.  
T he p r o p orti o n of s u bjects wit h P R U < 1 0 0  b y assess me nt ti me ( 0 t o 6 0  mi n utes) will be 
pl otte d as bar c h arts.   
De scri pti ve  statistics  of  P R U  relati ve  c h a n ge  fr o m  baseli ne  at  eac h  ti me  p oi nt  will  be 
pr o vi de d,  w here  c h a n ge  fr o m  baseli ne  is  defi ne d as  t he  rati o  of ([P R U  at  ti me  t  – P R U 
pre - d ose] / P R U pre- d ose) e x presse d i n perce nta ge.  
6. 8. 2. 3  S u p p ortive/se nsitivity a n alyses  
N o t a p plica ble. 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 2 1 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
6. 8. 2. 4  S u b gr o u p a n alyses 
Descri pti ve s u m mari es will be pr o vi de d f or eac h sec o n dar y P D e n d p oi nt , i.e., P D pr ofile 
o ver ti me, a n d P R U 6 0 m stat us, usi n g t he sa me s u b- gr o u ps as defi ne d i n Secti o n 6. 8. 1. 4. 
6. 8. 3  H a n dli n g of missi n g d at a  
N o i m p utati o ns are pla n n e d.  
S u bjects f or w h o m deter mi nati o n of t he P D res p o nse is n ot p ossi ble will n ot be i ncl u de d 
i n t he c o m p utati o n of res p o nse rate f or t he mai n a nal ysis. 
T he s a me a p pr o ac h will b e c o nsi dere d f or t he e x pl orat or y e n d p oi nt P D res p o n se wit hi n t he 
1 st h o ur. 
6. 9  A n al ysis of p h a r m ac o ki netic v ari a bles 
T he P K v aria bles  will be s u m marize d a n d liste d as pr o vi de d usi n g t h e P K  s et a n d will use 
t he st u d y treat me nt recei ve d. 
T he plas ma P K p ar a meters of A C T -2 4 6 4 7 5 will be deri ve d b y n o n -c o m p art me ntal  a nal ysis 
of  t he  plas ma  c o nce ntrati o n -ti me  pr ofiles.  P K  e n d p oi nts are: Ma xi m u m  plas ma 
c o nce ntr ati o n ( C ma x ), a n d  ti me t o reac h Cma x  (tma x ).  
L o g -tr a nsf or m e d val ue of Cma x  will be use d i n t he a nal ysis, w hile tma x  will b e use d as is .  
T he P K para meters tma x , a n d l o g( C ma x ) will be s u m marize d b y d ose gr o u p usi n g descri pti ve 
statistics,  i.e., arit h metic  mea n,  S D,  ge o metric  mea n,  mi ni m u m,  me dia n,  ma xi m u m, 
sta n dar d  err or,  a n d t w o-si de d  9 5 % CI  of  t h e  mea ns  a n d  c o effi cie nt  of  v ariati o n  i n  %. 
Gra p hical re prese nt ati o n of P K res ults o ver ti me will be pr o vi de d usi n g b o x -w his ker pl ots.  
N ote t hat f or t ma x , t he ge o metric mea n a n d its 9 5 % CI will n ot be calc ulate d. 
7  
S A F E T Y V A RI A B L E S A N D A N A L Y S E S 
7. 1  O ver vie w of s afet y a n al yses i ncl u di n g s u b g r o u p a n al yses 
F or  cate g orical  varia ble s, t he  i nci de nce  of  s u bjects  b y  cate g or y  will  be  s u m marize d  b y 
usi n g fr e q ue n c y c o u nts, a n d perce nt a ges.  
C o nti n u o us  varia bles  will  be  s u m marize d  usi n g:  arit h metic  mea n,  S D,  mi ni m u m, 
1 st q uartile, me dia n, 3r d q uartile, a n d ma xi m u m.  
N o s u b- gr o u p a n al ys es ar e pla n ne d f or safet y d ata.  
7. 2  A d verse e v e nts  
T he ha n dli n g of missi n g or i nc o m plete date/ti me of a d verse e v e nts ( A Es ) a n d assess me nts 
is descri be d i n A p pe n di x D. 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 2 2 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
7. 2. 1  V ari a bles  
7. 2. 1. 1  All a dve rse 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 C R F f or m re gar dless of t he o nset 
date.  
7. 2. 1. 2  Tre at m e nt -em er ge nt a dverse eve nts  
Treat me nt -e mer ge nt A Es  ( T E A Es) are t h os e A Es wit h o nset date/ti me ≥ date/ti me of st u d y 
dr u g a d mi nistrati o n a n d ≤ 4 8 h after dat e/ti me of st u d y treat me nt a d mi nistrati o n.  
A n A E f or w hic h ti me of o nset is missi n g will be c o u nte d as treat me nt -e m er ge nt if o nset 
d ate  is ≥ date of st u d y dr u g a d mi nistrati o n a n d is ≤ date of st u d y treat me nt a d mi nistrati o n 
+ 2  da ys.  A n A E  wit h  o nset  ti me  missi n g,  a n d  e n d  date  a n d  ti me  are  i de ntical  t o  st u d y 
treat me nt start date a n d ti me, is n ot a treat me nt e m er ge nt A E. 
7. 2. 1. 3  Tre at m e nt -em er ge nt a dverse eve nts  rel ate d t o st u dy tre at m e nt  
T E A Es  rel ate d  t o  st u d y  dr u g  are  t h os e  T E A Es  w hic h are re p orte d  as  relate d  t o  st u d y 
treat me nt b y t he i n vesti gat or. 
7. 2. 1. 4  Tre at m e nt -em er ge nt a dverse eve nts by i nte nsity  
A E  i nte nsit y  is  re p ort e d  b y t h e i n vesti gat or  usi n g  t he  f oll o wi n g se v erit y scal e: m il d, 
m o derate, or s e ver e.  
F or A Es wit h m ulti ple i nte nsities  re p orte d, t he w orst re p orte d se verit y will be c o nsi dere d.  
7. 2. 1. 5  Seri o us a dverse eve nts  
A seri o us A E ( S A E) is an A E t hat has b ee n re p orte d as s eri o us b y t h e i n vesti gat or i n t h e 
C R F.  
7. 2. 1. 6  A dverse  eve nts le a di n g t o de at h 
A n A E will be  c o nsider e d as lea di n g t o deat h  if t h e A E o utc o me is fat al. 
7. 2. 1. 7  A dverse eve nts le a di n g t o st u dy tre at m e nt disc o nti n u ati o n 
N ot a p plica ble.  
7. 2. 1. 8  Ot her a dverse eve nt c ate g ories  
T w o  A Es  of  s p ecial  i nterest  ( A E SIs)  are  defi n e d,  o ne will  i ncl u de  a n y  A E  i ncl u de d  i n 
Me d D R A S M Q “ Hae m orr ha ge (e x cl. la b)”  of narr o w ter ms , t he ot her will i ncl u de a n y A E 
i ncl u de d i n t he Me d D R A hi g h le vel gr o u p t er m " A d mi nistrati o n site reacti o n"  
A E SIs will be s u m marize d a n d liste d .  


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 2 3 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
7. 2. 2  A n al ysis 
F or all  t he A E vari a bles descri be d i n Secti o n 7. 2. 1 , t he i nci de nce of s u bjects wit h T E A Es  
will be s u m marize d (fre q ue nc y c o u nts a n d p erce nt a ges) b y S O C a n d/ or P T . 
F or  T E A Es  b y  i nte nsit y,  t he  i nci de nce  of  s u bjects  wit h  e ve nt s will  be  s u m marize d 
(fre q u e nc y c o u nts a n d perce nta ges) b y S O C a n d/ or P T  a n d b y ma xi m u m i nte nsit y ( w orst).  
All  A Es  will  be  liste d  se parat el y  f or  s u bjects  i ncl u de d  i n  t he  S A F  a n d  f or  s u bjects  n ot 
i ncl u de d i n t he S A F. S A E s will be fla g ge d. 
Listi n gs will als o be pr o vi de d f or S A Es a n d A E SIs f or t he S A F o nl y. 
7. 2. 3  A n al yses f or ke y st u d y d at a discl os ure t o re g ul at or y a ut h orities  
T he  a nal yses  d escri b e d  i n  Secti o n 7. 2. 2 will  als o  be  perf or me d  o n  n u m ber  of  e v e nt 
occ urr e nces,  i.e. , s u m marizi n g  t he  t otal  n u m ber  of e ve nts,  f or  S A Es,  treat me nt -relate d 
S A E, a n d n o n-seri o us A Es. 
7. 3  De at h 
Deat h will b e  c o nsi dere d t o ha ve occ urre d if a pri mar y ca us e of deat h is re p orte d i n t h e 
C R F ‘Deat h ’ f or m. 
T he  ori gi nal  ter ms  use d  b y  t he  i n vesti gat ors  t o  descri be  deat hs  (i.e.,  d eat h  ca use)  are 
assi g ne d P T s  f or  classificati o n  a n d  ta b ulati o n  usi n g  t he  latest  i m ple me nte d  Me d D R A 
versi o n dicti o nar y. 
Deat h will be classifie d as o n st u d y deat hs (fr o m st u d y start t o E n d - of-St u d y [ E O S] ) a n d 
treat me nt-e mer ge nt  deat hs ( wit hi n 2 da ys fr o m st u d y dr u g a d mi nistrati o n).  
All deat hs i ncl u di n g ca us e of deat h will be liste d, a n d fla g ge d as p er peri o d of occ urre n ce 
(scree ni n g a n d treat me nt peri o ds). 
7. 4  L a b or at or y tests 
7. 4. 1  Me as ure me nts  
E x ce pt c oa g ulati o n test (acti vate d cl otti n g ti me) p erf or me d l ocall y a n d use d f or t he a nal ysis 
descri be d  i n  t his  secti o n,  o nl y  la b orat or y  data  recei ve d  fr o m  t he  ce ntral  la b orat or y  [see 
pr ot oc ol secti o n 7. 2. 5. 2] will be i ncl u de d i n t he a n al yses d escri b e d i n t his secti o n.  
H o we ver, all la b orat or y  data  recei ve d  fr o m  l ocal  la borat orie s  will be  i ncl u de d  i n  t he 
listi n gs.  
Treat me nt -e mer ge nt  la b orat or y  a b n or malities  are ce ntral  la b orat or y a b n or malities f or 
w hic h bl o o d sa m ple c ollecti o n were c ollecte d at ti me of st u d y dr u g a d mi nistrati o n or wit hi n 
t he first 4 8 h o urs ( 2 da ys) after st u d y a d mi nistrati o n, a n d t hat were n ot prese nt at baseli ne.  


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 2 4 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
W orst  treat me nt-e mer ge nt  mar ke d  l a b orat or y  a b n or malities  [see A p pe n di x C]  will  be 
s u m marize d b y d ose gr o u p. 
7. 4. 2  A n al ysis 
Descri pti ve  s u m mar y  statistics  b y  visit  a n d st u d y treat me nt  gr o u p will   be pr o vi de d  f or 
o bser ve d val ues a n d, w h e n re p orte d at baseli ne a n d p ost -baseli ne,  a bs ol ute c ha n ges fr o m 
baseli ne b y cate g or y ( he mat ol o g y/ c oa g ul ati o n, c he mistr y) a n d b y para met er. Data will be  
dis pla ye d i n SI u nits as pr o vi de d b y t he ce ntral la b orat or y. 
Tr eat me nt -e mer ge nt l a b orat or y a b n or malities  will be s u m marize d b y la b orat or y cate g or y, 
varia ble a n d s e verit y  ( m ar ke d la b orat or y a b n or m alit y).  
O nl y s u bject s at ris k, i.e., wit h n o mar ke d a b n or malit y pres e nt pri or t o st u d y dr u g start, 
will be i ncl u de d  i n t hese a nal ys es . 
F or eac h la b or at or y cate g or y, a listi n g of t he val ue at eac h ti me p oi nt, i n SI u nits, f or all 
varia bles a n d  t he  c h a n ges  fr o m  bas eli ne  (c o nti n u o us  a n d  cat e g orical) , as well  as  t he 
a b n or malit y  gr a de/ fla g  will  be  pr o d uce d  a n d  will  i ncl u de  all  visits.  T he  val ues  n ot 
c o nsi dere d i n t he a n al yses , i.e., l ocal l a borat ori e s, will be fla g ge d.  A listi n g of s u bjects wit h 
at least 1 mar ke d l a b orat or y a b n or malit y will als o be pr o vi de d. 
7. 5  Electr oc ar di o gr a p h y a n al ysis 
N ot a p plica ble. 
7. 6  Vit al si g ns a n d b o d y w ei g ht 
7. 6. 1  Bl o o d press ure a n d p ulse r ate a n al ysis 
T his i ncl u des t he s yst oli c a n d  diast olic bl o o d press ures (sitti n g a n d/ or s u pi ne), a n d p ulse 
rate. 
S yst olic a n d diast olic bl o o d press ures will be s u m marize d re gar dl ess of t he s u bject p ositi o n 
at ti me of meas ure.  
A listi n g of val u e s, i n SI u nits, f or all varia bl es a n d t he c ha n ges fr o m baseli ne (c o nti n u o us 
a n d cate g orical) as  w ell as t he a b n or malit y gra de/ fla g will be pr o d uce d a n d i ncl u des all 
ti me p oi nts. T he val ues n ot i ncl u de d i n t he a nal yses will be fla g ge d.  
F or eac h para meter at eac h ti me p oi nt o ver t he c o urse of t he st u d y, q ua ntitati ve descri pti ve 
statistics f or t he val ue a n d t he c ha n ge fr o m baseli ne will be prese nte d b y para meter, b y 
ti me p oi nt a n d treat me nt gr o u p.  
7. 6. 2  B o d y w ei g ht, a n d o t her vit al si g n a n al yses 
B o d y we i g ht val ues  a n d assess me nt  date will be liste d.  


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 2 5 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
7. 7  Ot her s afet y v ari a bles a n d a n al yses 
N ot a p plica ble.  
8  
G E N E R A L S T A TI S TI C A L M E T H O D O L O G Y 
Data will be a n al yze d usi n g S A S versi o n 9. 4 or hi g her. 
8. 1  Ge ner al r ules f or d at a prese nt ati o ns 
Ge ner al  r ules  f or  data  prese nta ti o ns  as  des cri be d  bel o w  are  f oll o we d  u nless  ot her wise 
s pecifie d. 
D ata  ar e  liste d  a n d  s u m marize d  b y  descri pti ve  statistics  (ta bles  or  fi g ures)  as  descri be d 
bel o w. 
8. 1. 1  Tre at me nt g r o u ps  
T he st u d y i ncl u de d t he f oll o wi n g 2 gr o u ps c orres p o n di n g t o t he 2 st u d y treatme nt gr o u ps 
(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 ). All a nal yses , u nless st ate d ot her wise, 
will be re p orte d b y t h ose 2 treat me nt ar ms, a n d o v erall, i n t his or der. 
8. 1. 2  Descri pti ve st atistics  
Descri pti ve statistics will be pr o vi de d b y d ose gr o u p  a n d o veral l, de p e n di n g o n t he nat ure 
of t he criteri a:  
Q u a ntit ati ve:  
N u m ber  of  o bser v e d  val ues,  mea n,  S D,  mi ni m u m  a n d  ma xi m u m,  me dia n, 1 st a n d  3 r d 
q uartiles.  
Q u alit ati ve:  
N u m ber of o bs er v e d val u es, n u m ber of missi n g v al ues, n u m ber a n d perce nt a ge of s u bjects 
per le vel/ cate g or y.  
U nless ot her wise s pecifi e d i n t he ta ble s hells, t he perce nt a ge calc ulati o n will n ot c o nsi der 
missi n g val ues i n de n o mi nat ors. 
T he  n u m ber  of  missi n g  val ues  is  dis pla ye d  o nl y  if  >  0.  F or  cate g orical  varia bles ,  t h ose 
missi n g are dis pla ye d aft er t he las t cate g or y a n d n o perce nt a ge is re p orte d. 
Listi n gs  ar e  gr o u p e d  b y  d ose  gr o u p  (sa me  or d er  as  i n  t a bles  hea ders,  if  a p plica ble, 
scree ni n g f ail ures are liste d last).  
Ra w  data  listi n gs , if  re q uire d, are  base d  o n  datasets  as  recei ve d.  All  data  c ollecte d  are 
dis pla ye d, i ncl u di n g u nsc he d ule d visits (if a n y). 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 2 6 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
8. 2  Effic ac y a n al yses 
N ot a p plica ble.  
9  
I N T E RI M A N A L Y S E S  
N ot a p plica ble.  
1 0  G E N E R A L D E FI NI TI O N S A N D D E RI V A TI O N S 
1 0. 1  A n al ysis peri o ds a n d visit wi n d o ws 
T he  treat me nt  peri o d  is  defi ne d  as  t he  peri o d  starti n g  f r om 
ti me  of stu d y  dr u g 
a d mi nistrati o n u p t o 4 8 h o ur s p ost a d mi nistrati o n. H o we ver, s o me assess me nts ma y o nl y 
ha ve t he date re p ort e d a n d n o ti me re p orte d (eit her t he ti me was n ot pla n ne d t o be c ollecte d 
or is missi n g) . I n t his case it will be ass u me d t hat t he 4 8 h o urs treat me nt peri o d c orres p o n ds 
t o t he da y of st u d y dr u g a d mi nistrati o n a n d t o t he t w o f oll o wi n g da ys ( 1st, 2n d a n d 3 r d da y 
of t he treat me nt p eri o d).  
T his ma y r es ult i n a n o ver-esti mate d d urati o n of t h e treat me nt peri o d f or t h ose e v e nts t hat 
d o n ot ha ve assess m e nt ti me. 
1 0. 2  D ates, ti mes a n d d a ys 
1 0. 2. 1  Defi niti o n of st u d y st art  
St u d y st art da y is t he da y of i nf or me d c o ns e nt si g n at ure. 
1 0. 2. 2  B aseli ne  
B aseli ne  is t he last n o n-missi n g assess me nt p erf or me d or v al ue meas ure d bef ore or o n t he 
da y a n d ti me of st u d y dr u g a d mi nistrati o n (i.e., pri or t o st u d y treat me nt a d mi nistrati o n), 
u nless ot her wise defi ne d i n t he s pecific a n al ysis secti o n. 
S u bjects  wit h o ut  a n y  data  f or  a  p ara m eter  b ef ore  treat me nt  a d mi nistrati o n  will  ha ve  a 
missi n g baseli ne ( a n d t heref or e a missi n g c ha n ge fr o m baseli ne) val u e f or t his para meter.  
If it is n ot p ossi ble t o all ocate a n e ve nt/ meas ure t o t he baseli ne peri o d ( missi n g dat e a n d/ or 
ti me), it will be  c o nsi dere d as bei n g p ost- bas eli ne.  
1 0. 2. 3  P ost -b aseli ne assess me nt  
P ost- baseli ne assess me nt is a n y ass ess me nt perf or me d after b aseli ne a n d u p t o E O S.  
1 0. 2. 4  Tre at me nt st art d at e/ti me  
Treat me nt start date/ti me  is t he date/ti me rec or de d i n t he ‘St u d y Treat me nt A d mi nistrati o n ’ 
C R F pa ge.  
1 0. 2. 5  Defi niti o n of e n d of st u d y tre at me nt  
N ot a p plica ble. 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 2 7 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
1 0. 2. 6  Defi niti o n of E n d - of- St u d y 
E O S  f or  a  si n gle  su bject is  defi ne d  as  t he  da y w he n  safet y  f oll o w- u p assess me nts  are 
perf or me d .  
F or ra n d o mize d s u bjects w h o ne ver recei v e d t he st u d y treat me nt, E O S dat e is defi ne d as 
t he earliest date a m o n gst t he f oll o wi n g, as re p ort e d i n t he “St u d y Dis c o nti n uati o n ” C R F 
pa ge:  
1.  Date of last s uccessf ul c o ntact,  
2.  Date of s u bject decisi o n, 
3.  Date of p h ysicia n d ecisi o n,  
4.  Date of s u bject deat h , 
5.  Date s u bject w as i nf or me d of s p o ns or’ s decisi o n. 
1 0. 2. 7  Defi niti o n of scree ni n g f ail ure  
A s u bject is c o nsi dere d a scree ni n g fail ure if he/s he was not ra n d o mize d (i.e. , has n ot bee n 
assi g ne d a st u d y dr u g).  
1 0. 2. 8  Defi niti o n of pre m at ure st u d y disc o nti n u ati o n  
S u bjects are c o nsi dere d t o ha ve pre m at urel y disc o nti n ue d t he st u d y if  a reas o n f or st o p pi n g 
t he st u d y is pr o vi de d o n t he St u d y Disc o nti n uati o n C R F pa ge.  
T he  date  a n d  t h e  reas o n  f or  st u d y  disc o nti n uati o n  are  c ollecte d  i n  t he “St u d y 
Disc o nti n uati o n” f or m (a n d i n t he “Deat h ” f or m if t he s u bject die d). 
1 0. 3  Defi niti o n of re as o n f or scree ni n g f ail u re 
F or s u bject s w h o are c o nsi dere d  a scree ni n g fail ure , t he reas o n f or scree ni n g fail ure is as 
re p orte d i n t he C R F .  
1 0. 4  C o n ve nti o n f or de m o gr a p h y d at a c o nsi der e d f or a n al ysis w he n m ulti ple 
v al ues re p orte d 
F or s u bjects wit h m ulti ple bas eli ne ass ess me nt s, o nl y t he last v al ues are i ncl u de d i n a n y 
a nal ysis,  w hile all val ues  wil l be prese nte d i n t he listi n gs a n d date  of i nf or me d c o nse nt 
si g nat ur e will re mai n t he date of t he first si g nat ure.  
1 0. 5  C o di n g dicti o n a ries  
T he versi o n of Me d D R A  use d f or c o di n g me di cal hist or y a n d A Es  will be dis pla ye d i n 
statistical o ut p ut f o ot n otes. 
Si milar l y, t h e versi o n of t he W H O Dr u g Refere nce Listi n g dicti o nar y bas e d o n t he W H O 
A T C classificati o n s yste m use d f or c o di n g of pre vi o us a n d c o nc o mita nt t hera pies re p orte d 
i n t his st u d y will be dis pla ye d i n statistical o ut p ut f o ot n otes . 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 2 8 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
1 0. 6  Me dic al hist or y a n d c urr e nt (st u d y c o nc o mit a nt) me dic al c o n diti o ns  
Me dical hist or y a n d c urre nt me dical c o n diti o ns, i.e. , st u d y c o nc o mita nt me di cal c o n diti o ns, 
at baseli ne i ncl u de pre vi o us a n d/ or c o nc o mita nt pr oce d ures or dia g n os es. 
Me dica l  pr o ce d ures  will  be  i de ntifi e d  as me dica l hist or y ,  i. e., e n d e d  pri or  t o  i nf or m e d 
c o nse nt si g n at ure date, a n d as c o n c o mita nt , f or t h ose o n g oi n g at or aft er t h e si g n at ure date 
of t he i nf or me d c o ns e nt. 
If n o n e  a p pl y ,  pr oce d ures  a n d  dia g n oses  are  c o nsi dere d st u dy  c o n c o mit a nt me dic al 
c o n diti o ns . 
1 0. 7  Pre vi o us a n d c o nc o mit a nt me dic ati o n  
Previ o us me dic ati o ns  ar e defi ne d as a n y me di cati o n wit h a start date pri or t o st u d y start 
date [see d efi niti o n i n S ecti o n 1 0. 2. 1] a n d wit h a n e n d d ate (last a d mi nistrati o n) pri or t o 
st u d y start date.  
St u dy c o nc o mit a nt me dic ati o ns  are defi ne d as a n y me dicati o n t hat is o n g oi n g o n t he date 
w he n i nf or m e d c o ns e nt is o btai ne d, or i nitiate d at a n y ti me b et wee n st u d y start a n d u p t o 
E O S [see defi niti o n i n Secti o n 1 0. 2. 6] . 
St u dy- tre at me nt  co n c o mit a nt  me dic ati o ns  at  b aseli ne  (a  s u bs et  of  st u d y-c o nc o mita nt 
me dicati o ns) are  defi ne d  as  a n y  me dicati o n  wit h  “starte d  pri or  t o  first  st u d y  treat me nt 
a d mi nistrati o n”  i n dicate d  as  “ yes”  or  wit h a st art  date  bef ore  d ate  of  st u d y  treat me nt 
a d mi nistrati o n  a n d  is  eit her  o n g oi n g  at  e n d  of  st u d y  or  has  a n  e n d  d ate  after  t h e  st u d y 
treat me nt a d mi nistrati o n date. 
St u dy- tre at me nt c o nc o mit a nt me dic ati o ns (a s u bset of st u d y-c o nc o mita nt me dicati o ns) are 
a n y st u dy-tre at me nt  c o n c o mit a nt me dic ati o ns at  b a seli ne  a n d a n y  me dicati o ns i nitiate d 
wit hi n t he 4 8- h o ur ( 2- da y) p eri o d fr o m st u d y treat me nt a d mi nistrati o n.  
If n o e n d dat e is a vaila bl e f or a m e dicati o n, it is c o nsi dere d o n g oi n g at E O S . 
1 1  C H A N G E S O R C L A RI FI C A TI O N S T O A N A L Y S E S P L A N N E D I N 
T H E S T U D Y P R O T O C O L  
1 1. 1  C h a n ges t o t he a n al yses pl a n ne d i n t he st u d y pr ot oc ol 
1 1. 1. 1  C h a n ge i n se nsiti vit y a n al ysis 
T he  pr ot oc ol  i n dicate d  t hat t he se nsiti vit y  a n al ysis f or  t he  P D  e n d p oi nts was  t o  b e 
c o n d ucte d o n t he F A S. T his will n ot be perf or me d , as t he mai n differe n ce bet wee n t he F A S 
a n d  m F A S  is  t he  prese nce  of  a P R U  meas ure me nt  3 0  mi n utes  after  st u d y  dr u g 
a d mi nistrati o n, a c o n diti o n re q uire d t o perf or m t he a nal ysis o n t he F A S as n o i m p utati o n 
is pla n ne d f or t his e n d p oi nt. 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 2 9 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
1 1. 1. 2  St u d y dr u g e x p os ure  
T he pr ot oc ol s p ecifie d t hat st u d y dr u g e x p os ure was t o be a nal yze d o n t h e F A S a n d t h e 
P P S  (se nsiti vit y  a nal ysis).  T his  has  bee n  m o difie d  s o  t hat  t he  a nal ysis  of  st u d y  dr u g 
e x p os ure  is  perf or me d  o n   t he S A F, t he  defi niti o n  of  w hic h is t he sa me  as  t he  F A S  b ut 
pr o vi des better c o nsiste n c y f or safet y d ata i nter pretati o n.  
1 1. 2  C h a n ges i n t he c o n d u ct of t he st u d y / d at a c ollecti o n 
N ot a p plica ble.  
1 1. 3  Cl arific ati o ns c o ncer ni n g e n d p oi nt defi niti o ns a n d rel ate d v ari a bles or 
st atistic al met h o ds 
A n al ysis set  
T he P P S defi niti o n has bee n m o difie d t o use t he a nal ysis set use d f or a nal ysis of pri mar y 
e n d p oi nt as a refer e nce. I nstea d of usi n g t h e F A S as t he refere nce set t o d efi ne t he P P S, t he 
m F A S is use d a n d is m ore r ele va nt as t his a nal ysis set is t he o ne us e d f or perf or mi n g t h e 
a nal ys es o n t he pri mar y P D e n d p oi nt. 
T he p rot oc ol i n dicate d t hat a nal ysis of de m o gr a p hics c h ar acteristics  w o ul d be perf or me d 
o n t he R N D o nl y if t here was a differe nce bet wee n t he R N D a n d  t he set us e d f or t he mai n 
a nal ysis ( F A S). T he S A P n o w re q uir es t hat t his a nal ysis is perf or me d o n t h e R N D as wel l, 
re gar dl ess of t he differ e n ce t o t he F A S, u nless t he R N D i ncl u des e x actl y t h e sa me s u bjects, 
i n w hic h case t he a nal ysis o n t he R N D is n ot nee d e d. 
1 1. 4  A d diti o n al a n al yses as c o m p are d t o t he st u d y pr ot oc ol 
N ot a p plica ble.  
1 2  LI S T O F T A B L E S, LI S TI N G S A N D FI G U R E S 
A c o m plete list of ta bles, listi n gs a n d fi g ures  is pr o vi de d i n t he S A P A p pe n dix - List of 
st atistic al o ut p uts d oc u me nt. 
 
 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 3 0 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
1 3  A P P E N DI C E S 
A p pe n di x A  
Pr ot oc ol s y n o psis 
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 pe n -la bel,  ra n d o mize d  st u d y  t o  assess  t he 
o nset  of  platel et  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. 
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 o car di al  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 Y 1 2 rece pt or 
a nta g o nists, a ntic oa g ula nts). 
Ot her 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 mac 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 pecti ve,  m ulti -ce nter,  o pe n -la bel,  ra n d o mize d, 
parallel -gr o u p,  P has e  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  ele 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 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 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 n al 
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 v es  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. 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 3 1 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
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 - of-St u d y ( E O S) assess 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 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)  I nf or me d  c o nse nt  o bt ai ne d  pri or  t o  a n y  st u d y-m a 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 us al  fe males 
a ge d  u p  t o  8 5  years.  P ost me n o pa usal  is  d efi 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 pe  I  A MI  i ncl 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 persiste nt S T -se g me nt ele v ati 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 me nt el e vati o n a n d 
ele vate 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). 
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 se v ere h e 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 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 nal  bl ee 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  ri s 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 ulati o n  t h era p y  wit hi n  7  da ys  pri or  t o 
ra n d o mizati o n. 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 3 2 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
7)  Pla n ne d  fi bri n ol ytic  t hera p y  or  a n y  fi bri n ol ytic  t hera p y 
a d mi nistere d wi t 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 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 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  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 nes s,  ne ur o de ge nerati ve  diseas e,  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  w ell  wit h  t he  i n vesti gat or  i n  t h e  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 v e 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 d er f or t he st u d y 
i nter pretati o n. 
1 2)  Cli nicall y rele 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 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 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 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 he 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 o c 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  wate r  f or 
i njecti o n.  F urt her  dil uti o n  wit h  1  m L  N a Cl  0. 9 %  will  be 
perf or me d  f or  pre parati 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 m e 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). 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 3 3 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
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 ul a 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 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 versi 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., str e 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,  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. 
•  Oral  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 he 
3 0 mi n  p ost -d ose  ti me  p oi nt,  as  meas ure d  via  V erif 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 %. 
S af et y e n d p oi nts  
T he  safet y  e n d p oi nts  will  be  assess e 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 v erse  e ve 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. 
                                                 
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  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 3 4 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
•  C ha n ge i n vital si g ns (s yst olic a n d diast olic arteri al bl o o d 
press ure a n d p ulse rate) fr o m baseli ne t o all ass esse 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 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 d p 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 n e d  a n al ysis  set  i ncl u des  all  s u bjects  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 n al ysis set  ( F A S) i ncl u des all ra n d o mize d s u bjects 
w h o ha ve b ee 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 me 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 uat e  
esti mati o n  of  t he  treat me nt  effects  (criteri a  f or  s uffici e 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 S A F w h o ha v e 
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 he 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 nal 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., 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 3 5 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
c o nsi deri n g 2 n ull h y p ot h eses ( pr o p orti o n of patie nts ac hie vi n g 
a res p o nse is less or e q ual t o 5 0 %) at 0. 0 2 5 t y p e 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 heses 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  ass ess me nt  will  be 
re place d.  
A o ne -si de d z-test will be c o m p ute d an d t he 9 5 % c o nfi de n ce 
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  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 he  pr o p orti o n  of  s u bjects  ac hi e vi n g  a  res p o ns e 
(i.e., P 2 Y1 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 de 2 1 s u bjects e val ua ble 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 hes es  (testi n g  eac h  d ose  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 ns e rat e u n der t he 
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 on 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  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 3 6 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
S T U D Y C O M MI T T E E S  
T he I n d e pe n de 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 d ata 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 p e 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 he I S E C has o verall res p o nsi bilit y f or safe g uar di n g t h e 
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 d ati o ns base d o n t he 
re p orte d  d ata.  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 o c us  o n  st u d y- dr u g-relat e d 
cli nicall y  rele v a nt  maj or  blee di n g  e ve nts,  acc or di n g  t o  t h e 
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  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 3 8 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
P er Pr ot oc ol set  
S u bj ect wit h c o nc o mita nt plat elet 
dis or ders  
at least o ne rec or d wit h I E.I E T E S T C D 
= E X C L 0 8  
P er Pr ot oc ol set  
S u bj ect wit h c o nc o mita nt dise ase or 
c o n diti o n t hat ma y ha ve pre ve nte d 
s u bj ect fr o m c o m plai ni n g wit h st u d y 
re q uire me nts of ma y be a c o nf o u n der 
of st u d y i nter pretati o n.  
at least o ne rec or d wit h I E.I E T E S T C D 
i n( E X C L 1 2, E X C L 1 4, E X C L 1 5) 
P er Pr ot oc ol set  
I nc orrect a d mi nistrati o n of t he st u d y 
dr u g  
D V. D V R E FI D = 0 2 C 0 1, 0 2 C 0 2  
P er Pr ot oc ol set  
3 0 -mi n ute  p ost -d ose Verif y N o w ®  
bl o o d sa m ple c ollecte d o utsi d e of t he 
pr ot oc ol -defi ne d wi n d o w  
D V. D V R E FI D = 0 3 F 0 3  or c o m p ute d 
as nee d be  
P er Pr ot oc ol set  
Iss ues wit h bl o o d sa m ple c olle cti o n  
or pr ocessi n g  f or platelet a g gr e gati o n 
assa ys  
D V. D V R E FI D = 0 3 F 1 0, 0 3 F 0 8  
P er Pr ot oc ol set  
Treat me nt wit h f or bi d de n i. v. platelet 
i n hi bit ors bef ore assess me nt of t he 
3 0 -mi n ute  ti me p oi nt. 
D V. D V R E FI D = 0 4 A 0 2  
P K set  
S u bj ect d oes n ot ha ve at least o ne 
plas ma  c o nce ntrati o n meas ure me nt 
after a d mi nistrati o n of st u d y 
treat me nt 
all P C. P C S T R E S C = « » w he n 
P C. P C T P T n ot P R E -D O S E  
A MI, ac ute m y o car dial i nfarcti o n; i. v., i ntra ve n o us; P K, p h ar mac o ki n etic set.  
 
 




A C T- 2 4 6 4 7 5 
St u d y I D- 0 7 6 A 2 0 2 
Fi n al Versi o n 1 
2 9 N o ve m ber 2 0 1 8, p ag e 4 0/ 4 1 
C o nfi de nti al  
St atistic al A n al ysis Pl a n f or 
Cli nic al St u d y Re p ort 
D oc N o D- 1 8. 2 0 4 
 
A p pe n di x D  
H a n dli n g of missi n g or  i nc o m plete d ate a n d/ or ti me 
T his secti o n descri bes s o me ge neral pri nci ples t o be f oll o we d i n t he case of  missi n g or 
i nc o m plete date/ti me. 
N ote t hat u nless n ote d ot her wise , t he n o n-i m p ute d date/ti me will be re p orte d i n listi n gs. 
A n i nc o m pl ete ( missi n g da y or m o nt h) or missi n g A E/c o nc o mita nt t hera p y date will be 
i m p ute d as descri be d i n Ta ble 5. T he ‘l o wer li mit’ a n d ‘ u p per l i mit’ refer t o t he earliest 
a n d latest p ossi ble dates, res pecti vel y. 
As a n e xa m ple: If t he start date is M A R 2 0 1 7 ( missi n g da y), t he l o wer li mit is 0 1 M A R 2 0 1 7 
a n d t he u p per li mit is 3 1 M A R 2 0 1 7; If t he start date is 2 0 1 7 ( mi ssi n g da y a n d m o nt h), t he 
l o wer li mit is 0 1J A N 2 0 1 7 a n d t he u p per li mit is 3 1 D E C 2 0 1 7. 
T a ble 5  
H a n dli n g of missi n g/i nc o m plete d ate a n d ti me 
T y p e of d ate 
D ate is i nc o m p lete
D ate is missi n g  
A E/ C M e n d date 
T he u p per li mit. 
N o re place me nt, t he A E/ me dicati o n is 
c o nsi dere d as o n g oi n g  i n t he a naly sis.
A E/ C M o nset date 
U nless, t he e ve nt is fla g ge d as St arte d pri or t o 
first  st u dy  tre at me nt  a d mi nistr ati o n o n t he 
C R F *, t he bel o w r ule a p plies.  
If t he (i m p ute d) res ol uti o n date is o n or after t he 
start of t he st u d y treat me nt a n d if t he start of t he 
st u d y treat me nt falls wit hi n t he u p per a n d l o wer 
li mits (i ncl usi ve), t he st u d y treat me nt start date 
is use d. 
If  t he  res ol uti o n  date  is  missi n g  a n d  t he  st u d y 
treat me nt  start date  falls  wit hi n  t he  u p per  a n d 
l o wer li mits (i ncl usi ve) t he st u d y treat me nt start 
date is use d. 
I n all t he ot her cases t he l o wer li mit is use d. 
If  t he  e ve nt  is  fla g ge d  P RI O R  T O  FI R S T 
D O S E *; t he st u d y treat me nt start date – 1 d a y  is 
use d. 
W hic he ver  is  t he  earlier  of  t he  date  of 
res ol uti o n  a n d  t he  <st u d y  treat me nt > 
start date. 
A E, a d verse e ve nt; C M, c o nc o mita nt me dicati o n; C R F, case re p ort  f or m. 
Me dical hist or y dates will n ot be i m p ute d. If se parate re p orts nee d t o be d o ne f or pre vi o us  or c o nc o mita nt me dicati o n, 
t he fla g o n t he C R F * * will be use d. 
* Fla g f or c o nc o m ita nt me dicati o ns: St arte d pri or t o first st u dy  tre at me nt a d mi nistr ati o n a ns were d Yes  o n t he C R F 
Previ o us/ C o nc o mit a nt Me dic ati o n  pa ge, 
* * Fla g f or me dical hist or y: O n g oi n g at I nf or me d C o nse nt si g n at ure  a ns were d Yes  o n t he C R F Me dic al Hist ory  pa ge. 
 
 


A C T -2 4 6 4 7 5  
St u d y  I D-0 7 6 A 2 0 2  
Fi n al Versi o n 1  
2 9  N o ve m ber 2 0 1 8, pa ge 4 1 /4 1  
C o nfi de nti al  
St atistic al A n al ysis Pl a n  f or 
Cli nic al St u d y Re p ort  
D oc N o  D-1 8. 2 0 4  
 
A p pe n di x E  
D oc u me nt hist or y  
Versi o n  
Eff ecti ve D ate  
Re as o n  
Fi nal 1  
2 9 N o ve m ber 2 0 1 8  
Ne w d oc u me nt