Clinical trial NCT05831644
Conditions: Type2diabetes Endothelial Dysfunction
Sponsor: Vicore Pharma AB
Start date: 2023-03-31; Completion date: 2023-06-20
Enrollment: 11 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
This trial is a single-centre, randomized, double-blind, placebo-controlled, 2-way cross-over phase 1b trial evaluating the pharmacodynamic effect of C21 on endothelial dysfunction and safety in subjects with type 2 diabetes mellitus (T2DM).

Detailed description:

Arms: arm 1: A single dose of C21 at visit 2 followed by a single dose of placebo at visit 3. arm 2: A single dose of placebo at visit 2 followed by a single dose C21 at visit 3.
Interventions: intervention 1: C21
Intervention descriptions: intervention 1: C21 is an angiotensin II type 2 receptor agonist (ATRAG)

Protocol documents:
Prot_SAP_000.pdf: 
Cli nic al Tri al Pr ot oc ol  
Vic ore P h ar m a A B  
Versi o n: 2. 0  
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
C o nfi de nti al  
P a ge 1  of 5 0  
Cli nic al Tri al Pr ot oc ol  
Title:  
A r a n d o mize d, d o u ble-bli n d, pl ace b o -c o ntr olle d, 2- w a y cr oss - o ver tri al 
e v al u ati n g t he effect of C 2 1  o n e n d ot heli al d ysf u ncti o n a n d s afet y i n 
s u bjects wit h t y pe 2 di a betes mellit us  
S h ort Title:  
A tri al t o e v al u ate t he effect of C 2 1  o n e n d ot heli al d ysf u ncti o n i n 
s u bjects wit h t y pe 2 di a betes 
S p o ns or : 
Vic ore P h ar m a A B  
K or n h a mst or g 5 3 
S E - 1 1 1 2 7 St oc k h ol m  
S we de n  
Tri al I D:  
V P - C 2 1- 0 1 3 
E u dr a C T N o.: 
2 0 2 3- 0 0 0 1 6 8- 7 7 
I n vesti g ati o n al 
Me dici n al Pr o d uct s: 
C 2 1  
I n dic ati o n: 
T y pe 2 D i a betes M ellit us ( T 2 D M) 
P h ase:  
1 b  
Versi o n:  
2. 0  
D ate:  
0 3- M A R - 2 0 2 3
T his Cli nic al Tri al Pr ot oc ol is t he pr o perty of Vic ore P h ar m a A B a n d is a c o nfi de nti al d oc u me nt. It is n ot 
t o be c o pie d or distri b ute d t o ot her p arties wit h o ut writte n a p pr ov al fr o m Vic ore P h ar m a A B. 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 2  of 5 0  
 
 
 
 
 
 
S p o ns or ’s A p pr o v al of Cli nic al Tri al Pr ot oc ol 
 
T his trial pr ot oc ol was s u bject t o critical re vie w b y t he s p o ns or. T he i nf or mati o n it c o ntai ns is 
c o nsiste nt  wit h  c urr e nt  k n o wle d ge  of  t h e  ris ks  a n d  be nefits  of  t he  i n vesti gati o nal  me dici nal  
pr o d uct, as well as wit h t he et hical a n d scie ntific pri nci ples g o ver ni n g cli nical researc h as set o u t 
i n t he latest versi o n of t he Decl arati o n of Helsi n ki a n d t he c urre nt I nter n ati o nal C o nfere n ce o n 
Har m o nisati o n (I C H) G ui deli ne f or G C P. 
T his trial will be c o n d ucte d i n c o m plia nce wit h t he pr ot oc ol, G C P, a n d a p plica ble   re g ulat or y 
re q uire me nts. 
 
S p o ns or ’s Me dic al E x pert:  
 
 
   
 
 
 
Vic ore P har ma A B  
E- mail:  
 
  
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
 
 
Si g nat ure  
 
I n t he cas e of a me di cal e mer ge nc y, t he I n vesti gat or ma y c o ntact t he S p o ns or’s Me dical E x p ert.  
 
 
S p o ns or ’s St atistic al E x pert:   
 
 
    
 
 
 
   
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
 
 
Si g nat ure  
 
 
 
V P Cli nic al De vel o p m e nt :  
 
 
  
   
 
 
 
  
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
 
 
Si g nat ure  
 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 3  of 5 0  
 
 
 
 
 
 
Si g n at or y I n vesti g at or’s A p pr o v al of Cli nic al Tri al Pr ot oc ol  
 
T his trial will be c o n d uct e d i n c o m plia nce wit h t he pr ot oc ol, G C P, a n d t he a p plica ble re g ulat or y 
re q uire me nts. 
I c o nfir m t hat I a gr ee t o c o n d uct t his trial i n c o m plia nce wit h t he Declarati o n of Helsi n ki, t he 
c urre nt  I nt er nati o nal  C o nfere n ce o n  H ar m o nisati o n  (I C H) G ui deli ne f or  G C P  a n d a p plica ble 
re g ulat or y r e q uire me nts. 
F urt her m ore, I c o nfir m t hat I h a ve r ea d a n d u n derst o o d t he prese nt cli nical trial pr ot oc ol a n d a gree 
t o c o n d uct t he trial i n c o m plia nce wit h t his. I f ull y u n dersta n d t hat a n y c h a n ges fr o m t he cli nical 
trial pr ot oc ol c o nstit ute a de viati o n w hic h will be n otifie d t o s p o ns or. 
 
 
 
C o or di n ati n g 
I n vesti g at or:  
 
 
 
Pr of Ja n Nilss o n   
 
 
 
 
Cli nical Researc h Ce ntre 6 0: 1 3  
Ja n Wal de nstr ö ms gata 3 5 
S E - 2 1 4 2 8 Mal m ö 
P h o ne: 
  
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
 
 
Si g nat ure  
 
 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 4  of 5 0  
 
 
 
 
 
 
T A B L E O F C O N T E N T S 
S P O N S O R’ S A P P R O V A L O F C LI NI C A L T RI A L P R O T O C O L  ........................................ 2 
SI G N A T O R Y I N V E S TI G A T O R’ S A P P R O V A L O F C LI NI C A L T RI A L P R O T O C O L  ... 3 
1  
P R O T O C O L S U M M A R Y  ......................................................................................... 7 
2  
F L O W C H A R T  ........................................................................................................ 1 0 
3  
B A C K G R O U N D A N D R A TI O N A L E  .................................................................... 1 1 
3. 1  
E n d ot heli al D ysf u ncti o n ...................................................................................... 1 1  
3. 2  
C urre nt Tre at m e nt of E n d ot heli al D ysf u ncti o n  ............................................... 1 1 
3. 3  
C o m p o u n d 2 1 ....................................................................................................... 1 1  
3. 4  
R ati o n ale f or Tri al ............................................................................................... 1 3  
3. 5  
R ati o n ale f or Tri al Desi g n .................................................................................. 1 4  
3. 6  
R ati o n ale f or D ose a n d D osi n g Re gi me n ........................................................... 1 4  
3. 7  
Ris k -Be nefit Assess m e nt  ..................................................................................... 1 4 
4  
O B J E C TI V E S A N D E N D P OI N T S  ......................................................................... 1 7 
5  
T RI A L P O P U L A TI O N  ............................................................................................ 1 8 
5. 1  
Recr uit m e nt .......................................................................................................... 1 8 
5. 2  
Scree ni n g a n d E nr ol m e nt L o g  ............................................................................ 1 8 
5. 3  
I ncl usi o n Criteri a................................................................................................. 1 8 
5. 4  
E xcl usi o n Criteri a  ................................................................................................ 1 8 
5. 5  
Restricti o ns D uri n g t he Tri al  ............................................................................. 1 9 
5. 6  
Wit h dr a w al Criteri a  ............................................................................................ 2 1 
5. 7  
L ost t o F oll o w- u p  ................................................................................................. 2 2 
6  
T RI A L D E SI G N  ....................................................................................................... 2 4 
6. 1  
O ver all Tri al Desi g n  ............................................................................................ 2 4 
6. 2  
N u m ber of S u bjects  ............................................................................................. 2 4 
6. 3  
Tri al Di a gr a m ...................................................................................................... 2 4  
6. 4  
Tri al D ur ati o n ...................................................................................................... 2 4  
6. 5  
Sc he d ule of E ve nts  ............................................................................................... 2 5 
7  
T RI A L T R E A T M E N T  ............................................................................................. 2 6 
7. 1  
I n vesti g ati o n al Me dici n al Pr o d ucts ................................................................... 2 6 
7. 2  
P ac k a gi n g, L a beli n g a n d St or a ge ....................................................................... 2 6  
7. 3  
Tre at m e nt Assi g n m e nt  ........................................................................................ 2 7 
7. 4  
A d mi nistr ati o n of I n vesti g ati o n al Me dici n al Pr o d ucts .................................... 2 7  
7. 5  
C o m pli a nce C hec k a n d Dr u g Acc o u nt a bilit y  ................................................... 2 7 
7. 6  
O ver d ose  ............................................................................................................... 2 8 
7. 7  
Bli n di n g of t he Tri al  ............................................................................................ 2 8 
7. 8  
Pr oce d ures f or U n bli n di n g  ................................................................................. 2 8 
8  
A S S E S S M E N T S  ....................................................................................................... 2 9 
8. 1  
De m o gr a p hics a n d B aseli ne Assess me nts  .......................................................... 2 9 
8. 2  
P h ar m ac o d y n a mic Assess me nts  ......................................................................... 2 9 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 5  of 5 0  
 
 
 
 
 
 
8. 3  
S afet y Assess m e nts  .............................................................................................. 3 0 
8. 4  
Ot her Assess m e nts  ............................................................................................... 3 2 
9  
A D V E R S E E V E N T S  ................................................................................................ 3 3 
9. 1  
A d verse E ve nt D efi niti o ns  .................................................................................. 3 3 
9. 2  
Ot her Re p ort a ble I nf or m ati o n  ........................................................................... 3 3 
9. 3  
A d verse E ve nt Assess m e nt Defi niti o ns  .............................................................. 3 4 
9. 4  
Rec or di n g of A d vers e E ve nts  ............................................................................. 3 5 
9. 5  
Re p orti n g of Seri o us A d verse E ve nts  ................................................................ 3 6 
9. 6  
F oll o w- u p o n A d verse E ve nts  ............................................................................. 3 6 
1 0  
C H A N G E S T O T RI A L C O N D U C T  ....................................................................... 3 6 
1 0. 1  
Pr ot oc ol A m e n d m e nts  ......................................................................................... 3 6 
1 0. 2  
Pre m at ure Ter mi n ati o n of t he Tri al  .................................................................. 3 7 
1 0. 3  
Pre m at ure Ter mi n ati o n of a Tri al Site  .............................................................. 3 7 
1 1  
D A T A H A N D LI N G A N D R E C O R D K E E PI N G  .................................................. 3 8 
1 1. 1  
D at a M a n a ge m e nt ............................................................................................... 3 8  
1 1. 2  
D at a fr o m Cli nic al Tri al Site  .............................................................................. 3 8 
1 1. 3  
S o urce D at a  .......................................................................................................... 3 8 
1 1. 4  
C o di n g of D at a ..................................................................................................... 3 9  
1 1. 5  
S u bject C o nfi de nti alit y  ....................................................................................... 3 9 
1 2  
R E T E N TI O N O F D O C U M E N T S ........................................................................... 4 0 
1 3  
S T A TI S TI C A L M E T H O D S  .................................................................................... 4 1 
1 3. 1  
Ge ner al  ................................................................................................................. 4 1 
1 3. 2  
Deter mi n ati o n of S a m ple Size  ............................................................................ 4 1 
1 3. 3  
A n al ysis D at a Sets................................................................................................ 4 1  
1 3. 4  
S u bject Dis p ositi o n  .............................................................................................. 4 1 
1 3. 5  
P h ar m ac o d y n a mic A n al ysis ............................................................................... 4 2  
1 3. 6  
S afet y A n al ysis ..................................................................................................... 4 3  
1 4  
G O O D C LI NI C A L P R A C TI C E  ............................................................................. 4 4 
1 5  
E T HI C S  ..................................................................................................................... 4 4 
1 5. 1  
I n de pe n de nt Et hics C o m mittees / He alt h A ut h orities ..................................... 4 4 
1 5. 2  
I nf or m e d C o nse nt ................................................................................................ 4 4 
1 5. 3  
S u bject I nf or m ati o n C ar d  .................................................................................. 4 5 
1 5. 4  
S u bject Pri v ac y a n d D at a Pr otecti o n ................................................................. 4 5  
1 6  
A U DI T S A N D I N S P E C TI O N S  ............................................................................... 4 5 
1 7  
M O NI T O RI N G ......................................................................................................... 4 6 
1 8  
R E P O R TI N G O F R E S U L T S  .................................................................................. 4 6 
1 8. 1  
Cli nic al Tri al Re p ort  ........................................................................................... 4 6 
1 8. 2  
Use of I nf or m ati o n ............................................................................................... 4 6  
1 8. 3  
P u blic ati o n of Res ults  .......................................................................................... 4 6 
1 9  
I N S U R A N C E A N D LI A BI LI T Y............................................................................. 4 7 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 6  of 5 0  
 
 
 
 
 
 
2 0  
R E F E R E N C E S  ......................................................................................................... 4 8 
2 1  
A B B R E VI A TI O N S ................................................................................................... 4 9 
 
 
 




 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 8  of 5 0  
 
 
 
 
 
 
5)  C o ntrace pti ve use b y me n a n d w o me n of c hil d beari n g p ote ntial w hic h is hi g hl y 
effecti ve a n d c o nsiste nt wit h l ocal re g ulati o ns re gar di n g t he met h o ds of c o ntrace pti o n 
f or t h ose partici pati n g i n cli nical trials. 
E xcl usi o n Criteri a  
 
S u bjects m ust n ot e nter t he trial if a n y of t he f oll o wi n g e xcl usi o n criteria are f ulfille d:  
1)  C o nc urre nt seri o us me dical c o n diti o n w hic h i n t he o pi ni o n of t he in vesti gat or  
c o nstit utes a ris k or a c o ntrai n dicati o n f or t he partici pati o n i n t he trial or t hat c o ul d 
i nterfere wit h t he trial o bjecti ves, c o n d uct or e val uati o n. 
2)  K n o w n, acti ve he patitis B, C, or h u ma n i m m u n o deficie nc y vir us ( HI V) i nfecti o n ( i.e., 
HI V wit h a C D 4 c o u nt < 5 0 0 cells/ m m³).  
3)  I m paire d he patic f u ncti o n or cli nicall y si g nifica nt li ver disease, w hic h i n t he 
i n vesti gat or's o pi ni o n ma kes t he s u bject i na p pr o priate f or t his trial. 
4)  Se vere re nal i m pair me nt ( i.e., esti mate d gl o mer ular filtrati o n rate (e G F R) ≤3 0 
m L / mi n/ 1. 7 3 m2). 
5)  Pr ol o n ge d Q Tc F ( Q T i nter val wit h Fri dericia's c orrecti o n) ( > 4 5 0 ms), atrial 
fi brillati o n, cli nicall y si g nifica nt arr h yt h mia or ot her cli nicall y si g nifica nt a b n or malit y 
i n t he resti n g E C G at screee ni n g (Visit 1 ), as j u d ge d b y t he i n vesti gat or.  
6)  U nsta ble or deteri orati n g car diac c o n diti o n.  
7)  Hist or y of se vere aller g y/ h y perse nsiti vit y or o n g oi n g aller g y/ h y perse nsiti vit y, as 
j u d ge d b y t he in vesti gat or , or hist or y of h y perse nsiti vit y t o dr u gs wit h a si milar 
c he mical str uct ure or class t o a n y of t he I M Ps.  
8)  Pre g na nt or breast -fee di n g fe male s u bjects. 
9)  Mali g na nc y wit hi n t he past 5 years wit h t he e xce pti o n of i n sit u re m o val of basal cell 
carci n o ma a n d cer vical i ntrae pit helial ne o plasia gra de I.  
1 0)  Pla n ne d maj or s ur ger y wit hi n t he d urati o n of t he trial.  
1 1)  Treat me nt wit h t he me dicati o ns liste d bel o w wit hi n 1 4 da ys  pri or t o scree ni n g ( Visit 1) 
or a ntici pate d nee d f or s uc h me dicati o n d uri n g t he partici pati o n i n t his trial:  
•  
I ns uli n. 
•  
Gl uca g o n -li ke pe pti de- 1 (G L P - 1) a g o nists.  
•  
Str o n g C yt oc hr o me P 4 5 0 ( C Y P) 3 A 4 i n d ucers ( e. g., rifa m pici n, p he n yt oi n, 
car ba maze pi ne a n d St. J o h n's W ort).  
•  
Str o n g C Y P 3 A 4 i n hi bit ors (e. g. clarit hr o m yci n, ket oc o naz ole, nefaz o d o ne, 
itrac o naz ole, rit o na vir). 
•  
Warfa ri n, di g o xi n a n d ot her me dicati o n  w here t he d ose nee ds t o be i n di vi d uall y 
titrate d. 
•  
Narr o w t hera pe utic i n de x dr u gs t hat are s u bstrates of C Y P 1 A 2, C Y P 2 C 8, 
C Y P 2 C 9, C Y P 2 C 1 9, C Y P 3 A 4, or O A T P 1 B 1 . 
1 2)  C urre nt or pre vi o us partici pati o n i n a n y ot her cli nical trial w here t he s u bject has 
recei ve d a d ose of I M P wit hi n 1 m o nt h or 5 half-li ves of t he I M P, w hic he ver is l o n gest, 
pri or t o scree ni n g.  
1 3)  A b n or mal la b orat or y val ue at scree ni n g i n dicati n g a p ote ntial ris k f or t he s u bject if 
e nr olle d i n t he trial as e val uate d  b y t he in vesti gat or . 
I n vesti g ati o n al 
m e dici n al pr o d uct, 
d os a ge a n d m o de 
of a d mi nistr ati o n  
C 2 1  
C 2 1  is s u p plie d as a 5 0  m g  ca ps ule f or oral  a d mi nistrati o n.  C 2 1  2 0 0  m g  ( 4 ca ps ules)  will  be  
a d mi nistere d  as a si n gle oral  d ose.  
Place b o  t o C 2 1  




















 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 1 8  of 5 0  
 
 
 
 
 
 
5  
T RI A L P O P U L A TI O N  
Pr os pecti ve a p pr o v al of de viati o ns fr o m t he eli gi bilit y criteria, als o k n o w n as pr ot oc ol wai vers or 
e xe m pti o ns, is n ot per mitte d. 
5. 1  
Recr uit m e nt  
S u bjects will be recr uite d fr o m  t he trial site’s trial data base . 
5. 2  
Scree ni n g a n d E nr ol m e nt L o g  
I n v esti gat ors m ust kee p a rec or d of all scree ne d s u bjects e ve n if t he y were n ot s u bse q ue ntl y 
i ncl u de d i n t he trial. T his i nf or mati o n is necessar y t o verif y t hat s u bjects w ere sel ecte d wit h o ut 
bias.  
A scree ni n g n u m ber will be all ocate d t o eac h s u bj ect i n c o n necti o n t o t he i nf or me d c o ns e nt 
pr ocess at t he s cree ni n g visit ( Visit 1). T he scree ni n g n u m ber will all o w i de ntificati o n of s u bjects 
irres pecti ve of t heir p ossi ble eli gi bilit y f or t he trial. 
Scree n f ail ures are defi ne d as s u bjects w h o c o nse nt t o partici pate i n t he cli nical trial b ut d o n ot 
f ulfil all eli gi bilit y criteria a n d ar e n ot s u bse q ue ntl y i ncl u de d i n t he trial. A mi ni mal set of scree n 
fail ure i nf or m ati o n is re q uire d t o e ns ure tra ns pare nt re p orti n g of scree n fail ure s u bjects. Mi ni mal 
i nf or mati o n i ncl u des d oc u me ntati o n of si g ne d a n d date d i nf or me d c o nse nt f or m (I C F) a n d 
reas o n(s) f or scree ni n g fail ure. 
S u bjects w h o d o n ot meet t he criteria f or partici p ati o n i n t his trial ma y n ot be rescree n e d.  
5. 3  
I ncl usi o n Criteri a 
F or i ncl usi o n i n t he trial, s u bjects m ust f ulfil t he f oll o wi n g criteria:  
1)  Writte n i nf or me d c o ns e nt, c o nsiste nt wit h I C H- G C P R 2 a n d l ocal la ws, o btai ne d bef ore t he 
i nitiati o n of a n y trial-relate d pr oce d ure. 
2)  Male or fe m ale patie nt a ge d ≥ 4 0 years at t he ti me of t he scree ni n g visit ( Visit 1).  
3)  D oc u me nte d dia g n ose d wit h T 2 D M pri or t o t he scree ni n g vi sit ( Visit 1). 
4)  A n R HI s c ore ≤2 as assesse d b y E n d o P A T at t he ti me of t he scree ni n g visit ( Visit 1). 
5)  C o ntrace pti ve use b y me n a n d w o me n of c hil d beari n g p ote ntial w hic h is hi g hl y effecti ve a n d 
c o nsiste nt wit h l ocal re g ulati o ns re gar di n g t he met h o ds of c o ntrace pti o n f or t h ose 
partici pati n g i n cli nical trials.  
5. 4  
E xcl usi o n Criteri a  
S u bjects m ust n ot e nter t he trial if a n y of t he f oll o wi n g e xcl usi o n criteria are f ulfille d:  
1)  C o nc urre nt seri o us me dical c o n diti o n w hic h i n t he o pi ni o n of t he i n vesti gat or c o nstit utes a 
ris k or a c o ntr ai n dicati o n f or t he partici p ati o n i n t he trial or t hat c o ul d i nterfere wit h t he trial 
o bjecti ves, c o n d uct or e v al uati o n. 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 1 9  of 5 0  
 
 
 
 
 
 
2)  K n o w n, acti ve h e patitis B, C, or h u ma n i m m u n o deficie nc y vir us ( HI V) i nfecti o n ( i.e., HI V 
wit h a C D 4 c o u nt < 5 0 0 cells/ m m³).  
3)  I m paire d he p atic f u ncti o n or cli nicall y si g nifica nt li ver disease, w hic h i n t h e i n vesti gat or’s 
o pi ni o n ma kes t he s u bject i na p pr o priate f or t his trial. 
4)  Se vere r e nal i m pair me nt ( i.e., esti mate d gl o mer ular filtrati o n rate (e G F R) ≤3 0 m L / mi n/ 1.7 3 
m 2). 
5)  Pr ol o n ge d Q Tc F ( Q T i nt er val wit h Fri dericia’s c orrecti o n) ( > 4 5 0 ms), atri al fi brillati o n, 
cli nicall y si g nifica nt arr h yt h mia or ot her cli nicall y si g nifica nt a b n or malit y i n t he resti n g E C G 
at screee ni n g ( Visit 1 ), as j u d ge d b y t he i n vesti gat or. 
6)  U nsta ble or deteri orati n g car diac c o n diti o n. 
7)  Hist or y of se ver e aller g y/ h y perse nsiti vit y or o n g oi n g aller g y/ h y perse nsiti vit y, as j u d ge d b y 
t he i n vesti gat or, or hist or y of h y perse nsiti vit y t o dr u gs wit h a si milar c he mi cal str uct ure or 
class t o a n y of t he I M Ps. 
8)  Pr e g na nt or br east- f ee di n g fe male s u bjects. 
9)  Mali g na nc y wit hi n t he past 5 years wit h t he e x ce pti o n of i n sit u re m o val of basal cell 
carci n o ma a n d cer vical i ntrae pit helial ne o plasia gra de I.  
1 0)  Pla n ne d maj or s ur ger y wit hi n t he d urati o n of t he trial. 
1 1)  Treat me nt wi t h t he me di cati o ns liste d bel o w wit hi n 1 4 da ys pri or t o scree ni n g ( Visit 1) or 
a ntici pate d nee d f or s uc h me dicati o n d uri n g t he partici pati o n i n t his trial: 
•  I ns uli n. 
•  Gl uca g o n-li ke pe pti de- 1 ( G L P - 1) a g o nists. 
•  Str o n g C yt oc hr o me P 4 5 0 ( C Y P) 3 A 4 i n d ucers ( e. g., rifa m pici n, p he n yt oi n, 
car ba m aze pi n e a n d St. J o h n ’s W ort). 
•  Str o n g C Y P 3 A 4 i n hi bit ors ( e. g., clarit hr o m yci n, k et oc o naz ol e, nefaz o d o ne, itrac o naz ol e, 
rit o na vir). 
•  Warf ari n , di g o xi n a n d ot her me dicati o n w h ere t h e d ose nee ds t o be i n di vi d uall y titrate d. 
•  Narr o w t h era p e utic i n de x dr u gs t hat are s u bstrates of C Y P 1 A 2, C Y P 2 C 8, C Y P 2 C 9, 
C Y P 2 C 1 9, C Y P 3 A 4, or O A T P 1 B 1. 
1 2)  C urre nt or pre vi o us partici pati o n i n a n y ot her cli nical trial w here t he s u bject has recei ve d a 
d ose of I M P wit hi n 1 m o nt h or 5 half-li ves of t he I M P, w hic h e ver is l o n gest, pri or t o 
scree ni n g. 
1 3)  A b n or mal la b orat or y v al ue at scr ee ni n g i n dicati n g a p ote ntial ris k f or t he s u bject if e nr olle d 
i n t he trial as e val uate d b y t he i n vesti gat or. 
5. 5  
Restricti o ns D uri n g t he Tri al  
S u bjects m ust be willi n g t o c o m pl y wit h t he restricti o ns as o utli ne d i n  Secti o ns 5. 5. 1  a n d 5. 5. 2 . 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 2 0  of 5 0  
 
 
 
 
 
 
5. 5. 1  
Ge ner al Rest ricti o ns  
1.  C o ntrace pti o n re q u ir e me nts: W o me n of c hil d beari n g p ote ntial ( W O C B P) m ust practice 
a bsti ne nce (if t h at is t heir preferre d lifest yle) fr o m Visit 1 t o Visit 4, or m ust a gree t o us e a 
hi g hl y effecti ve m et h o d of c o ntrace pti o n wit h a fail ure rat e of < 1 % t o pre ve nt pre g na n c y 
(c o mbi ne d [ oestr o g e n a n d pr o gest o ge n c o ntai ni n g] h or m o nal c o ntrace pti o n ass ociate d wit h 
i n hi biti o n of o v ulati o n [ oral, i ntra va gi nal, tra ns der mal], pr o gest o ge n- o nl y h or m o nal 
c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n [ oral, i njecta bl e, i m pla nta ble], 
i ntra uteri ne de vice [I U D] or i ntra uteri ne h or m o ne-releasi n g s yste m [I U S]) fr o m at least 4 
wee ks pri or t o t he first I M P a d mi nistrati o n u ntil 4 wee ks after last I M P a d mi nistrati o n. T heir 
male part ner m ust a gree t o use a c o n d o m d uri n g t h e sa me ti me fra me, u nl ess he has ha d a 
de m o nstrate d s uccessf ul vasect o m y m ore t ha n 6 m o nt hs a g o. 
Males s h o ul d use c o n d o m a n d t heir fe mal e part n er of c hil d- b eari n g p ote ntial m ust use a 
c o ntracepti ve met h o d wit h a fail ure rate of < 1 % t o pre ve nt pre g na nc y (see a b o ve) a n d dr u g 
e x p os ure of a part n er a n d refr ai n fr o m d o nati n g s p er m fr o m t he dat e of d osi n g u ntil 3 m o nt hs 
after t he l ast I M P a d mi nistrati o n.  
2.  Meals a n d dietar y restricti o ns:  S u bje cts m ust fast f or at least 3 h o urs pri or t o a d missi o n t o t he 
trial site f or Visit s 2 a n d 3, a n d u ntil e n d of t he E n d o P A T assess me nt.  Water is all o we d  a d 
li bit u m, e xce pt f or 1 h o ur bef ore a n d 1 h o ur after I M P a d mi nistrati o n. 
3.  Alc o h ol: C o ns u m pti o n of alc o h ol is n ot all o we d fr o m 1 2 h o urs pri o r t o a d missi o n t o t he trial 
site f or Visits 2 a n d 3, a n d d uri n g t hese visits .  
4.  C offee , tea, a n d ot her caffei ne- c o ntai ni n g be vera g es: N o c offee , tea or ot her caffei ne -
c o ntai ni n g be ver a ges are all o we d fr o m 2 h o urs pri or t o a d missi o n t o t he trial site f or Visits 2 
a n d 3, a n d u ntil e n d of t h e E n d o P A T assess me nt.  
5.  Ta uri ne- c o ntai ni n g be ver a ges: Be vera ges c o nt ai ni n g ta uri ne, e. g., e n er g y dri n ks s uc h as Re d 
B ull a n d M o nster E ner g y, are n ot all o we d fr o m 2 h o urs pri or t o a d missi o n t o t he trial site f or 
Visits 2 a n d 3, a n d u ntil t he e n d of t he E n d o P A T assess me nt. 
6.  Nic oti ne: S m o ki n g or t he use of nic oti ne-c o nt ai ni n g pr o d ucts, i ncl u di n g n o n- t o bacc o oral 
nic oti ne pr o d ucts, is n ot all o we d fr o m 3 h o urs pri or t o a d missi o n t o t he trial site f or Visits 2 
a n d 3, a n d u ntil e n d of t h e E n d o P A T assess me nt. 
7.  Gra pefr uit a n d gr a pefr uit- c ontai ni n g pr o d uc ts: T h e c o ns u m pti o n of gra pefr uit a n d/ or 
gra pefr uit-c o ntai ni n g pr o d ucts s uc h as ja ms, jellies, preser v es,  a n d fr uit j uices is n ot all o we d 
fr o m 1 2 h o urs pri or t o u ntil 1 2 h o urs after I M P a d mi nistrati o n at Visits 2  a n d 3. 
8.  E xercise : S u bjects m ust r efrai n  fr o m stre n u o us e x ercise , d efi ne d as great er t ha n 7 0% of t he 
ma xi mal p ulse rate f or 1 h o ur or m ore, f or at least 1 2 h o urs pri or t o a d missi o n t o t he trial site 
f or Visits 2 a n d 3, a n d u ntil e n d of t he E n d o P A T assess me nts.  
9.  Bl o o d d o nati o n : S u bjects  m ust n ot d o nate bl o o d or plas ma fr o m t he scree ni n g visit u ntil 3 
m o nt hs after t he fi nal me dical e xa mi nati o n at t he e n d - of-tri al visit.  
1 0.  Partici pati o n i n ot her cli nical trials : S u bj ects are n ot all o we d t o partici pate i n a n y ot her 
i nter ve nti o nal cli nical tri al fr o m t he scree ni n g visit u ntil t he e n d- of-trial visit.  


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 2 1  of 5 0  
 
 
 
 
 
 
5. 5. 2  
Pri or a n d C o nc o mit a nt Me dic ati o n 
C o nc o mita nt me dicati o n  is defi ne d as a n y me di cati o n or vacci ne (i ncl u di n g o ver-t he-c o u nter, 
prescri pti o n me dici nes, r ecreati o nal dr u gs, vita mi ns, a n d/ or her b al s u p ple me nts) or ot her s pecific 
cate g ories of i nterest t hat t he s u bject is recei vi n g at t he ti me of e nr ol me nt or recei ves d uri n g t he 
trial.  
All pri or a n d c o nc o mita nt me dicati o n  ta ke n u p t o 2 wee ks pri or t o scree ni n g ( Visit 1) a n d u ntil 
t he f oll o w-u p visit ( Visit 4) s h o ul d be rec or de d.  
Pri or  a n d c o nc o mita nt m e dicati o n  m ust be rec or d e d al o n g wit h:  
•  Reas o n f or use. 
•  Dates of a d mi nistrati o n i ncl u di n g start a n d e n d dates.  
•  D osa ge i nf or m ati o n i ncl u di n g d ose a n d fre q ue nc y. 
T he me dical m o nit or s h o ul d be c o ntacte d if t h ere are a n y q u esti o ns re gar di n g pri or a n d 
c o nc o mita nt me dicati o n .  
T he c o nc o mita nt me dicati o n  wit h h ol ds re q uire me nts prese nte d i n Ta ble 2  m ust be e val uate d at 
scree ni n g ( Visit 1) a n d pri or t o perf or mi n g t he E n d o P A T at Visits 2 a n d 3. S u bjects vi olati n g a n y 
of t he re q uir e me nts ca n b e re -s c he d ule d f or a n e w v isit wit hi n less tha n 1 0 da ys. Re -sc he d uli n g 
ca n o nl y occ ur o nce p er visit. Wit h h ol di n g me dicati o n s h o ul d o nl y be d o ne if cli nicall y 
acce pta ble b as e d o n i n vesti gat or’s j u d ge me nt.  
T a ble 2. C o nc o mit a nt m e dic ati o n  wit h h ol d s re q uire me nts    
Ti me t o wit h h ol d  
T her a p y /su bst a nce  
2 wee ks  pri or t o Visit 1  
•  
See Secti o n 5. 4 , excl usi o n criteri o n 1 1. 
1 2 h o urs pri or t o trial site 
a d missi o n at Visits 2 a n d 
3 a n d u ntil 6 h o urs after 
d osi n g of I M P 
•  
C o nc o mita nt me dicati o ns t hat are se nsiti ve or m o deratel y se nsiti ve 
s u bstrates of C Y P 1 A 2, C Y P 2 C 8, C Y P 2 C 9, C Y P 2 C 1 9, C Y P 3 A 4 ( e. g., 
re p a gli ni de, pi o glit az o ne, l os art a n, li n a gli pti n, s ax a gli pti n, 
riv ar ox a b a n).  
•  
A n y s tati ns.  
1 2 h o urs pri or t o t rial site 
a d missi o n at Visits 2 a n d 
3 a n d u ntil e n d of t he 
E n d o P A T assess me nt  
•  
A n y o t her c o nc o mita nt me dicati o n . S u bjects will be i nstr ucte d t o 
bri n g t heir me dicati o n, if a n y, wit h t he m o n t he da y of t he E n d o P A T 
assess me nt  t o res u me t heir me dicati o ns ri g ht after t he c o m pleti o n of 
assess me nt . 
5. 6  
Wit h dr a w al Criteri a  
S u bjects are free t o disc o nti n ue t heir partici pati o n i n t he trial at a n y ti me a n d f or w hate v er reas o n 
wit h o ut affecti n g t heir ri g ht t o a n a p pr o priate f oll o w- u p i n vesti gati o n or t heir f ut ure care. If 
p ossi ble, t he reas o n f or wit h dra wal of c o nse nt s h o ul d be d oc u me nte d. 
S u bjects ma y be disc o nti n ue d fr o m t he trial at a n y ti me at t he discreti o n of t he i n vesti gat or. 
A s u bject w h o pre m at urel y disc o nti n ues part ici pati o n i n t he trial will al wa ys be as ke d a b o ut t he 
reas o n(s) f or disc o nti n uati o n a n d t he prese n ce of a n y A Es. If a s u bject wit h dra ws c o ns e nt, t he 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 2 2  of 5 0  
 
 
 
 
 
 
i n vesti gat or m ust as k t he s u bject if he/s he is willi n g, as s o o n as p ossi ble, t o be assesse d 
acc or di n g t o t h e pr oce d ures sc he d ule d f or t he e n d - of-trial visit ( Visit 4). A n y o n g oi n g A Es will 
be f oll o we d- u p as descri be d i n Secti o n 9. 6 . 
T he pri mar y r eas o n f or disc o nti n uati o n/earl y wit h dra wal m ust be s pecifie d i n t he e C R F a n d fi nal 
dr u g acc o u nt a bilit y m ust be perf or me d. If t h e reas o n f or disc o nti n uati o n was a n A E, t he A E m ust 
be s pecifie d i n t he e C R F.   
S u bjects w h o are pre mat urel y wit h dra w n fr o m t he trial f or a n y reas o n e xce pt t he occ urre n ce of 
A Es assesse d as relate d t o t he trial treat me nt, ma y be re place d.  
5. 6. 1  
Wit h dr a w al fr o m I M P 
A s u bject will be wit h dra w n fr o m I M P  treat me nt if a n y of t he f oll o wi n g occ urs:   
•  S p o ns or decisi o n t o st o p t he trial or t o st o p t he s u bject’s partici pati o n i n t he trial; reas o ns 
ma y i ncl u de me dical, saf et y, or re g ulat or y iss ues, or ot her reas o ns c o nsiste nt wit h 
a p plica ble la ws, re g ulati o ns, a n d G C P. 
•  Se vere n o n -c o m plia nce t o cli nical trial pr ot oc ol pr oce d ures, as j u d ge d b y t h e i n vesti gat or 
a n d/ or S p o ns or. 
•  It is t he wis h of t he s u bject f or a n y reas o n. 
•  T he i n vesti gat or j u d ges it necessar y d ue t o me dical reas o ns. 
•  Pre g na nc y. 
A s u bject wit h dra w n fr o m I M P at or after Visit 2 b ut bef ore Visit 3, s h o ul d n ot perf or m Visit 3 
b ut ret ur n t o t he trial site f or a n e n d- of-tri al visit ( Visit 4). 
5. 6. 2  
Wit h dr a w al fr o m Tr i al  
A s u bject will be wit h dra w n fr o m t he trial if a n y of t he f oll o wi n g occ urs:  
 
•  It is t he wis h of t he s u bject f or a n y reas o n.  
•  L ost t o f oll o w- u p. 
5. 7  
L ost t o F oll o w- u p  
A s u bject will be c o nsi dere d l ost t o f oll o w- u p if he/s he re p eate dl y fails t o ret ur n f or sc h e d ule d 
visits a n d is u na ble t o be c o ntacte d b y t he tri al site. 
T he f oll o wi n g acti o ns m ust be ta ke n if a s u bject fails t o ret ur n t o t he cli nic f or a re q uire d trial 
visit:  
•  T he site m ust atte m pt t o c o ntact t he s u bject a n d resc he d ule t he misse d visit as s o o n as 
p ossi ble, c o u nsel t he s u bject o n t he i m p orta nce of mai ntai ni n g t he assi g ne d visit sc he d ule 
a n d ascertai n w het h er t he s u bject wis hes t o a n d/ or s h o ul d c o nti n ue i n t he trial. 
•  Bef ore a s u bj ect is dee m e d l ost t o f oll o w- u p, t he i n vesti gat or or desi g nee m ust ma ke 
e ver y eff ort t o r e gai n c o ntact wit h t he s u bject ( w h ere p ossi ble, 3 tele p h o n e calls, a n d if 
necessar y, a certifie d lett er t o t he s u bject’s last k n o w n maili n g a d dress or l ocal e q ui vale nt 
met h o ds). T hese c o nt act att e m pts s h o ul d be d oc u me nte d i n t he s u bject’s me dical rec or d. 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 2 3  of 5 0  
 
 
 
 
 
 
•  S h o ul d t he s u bject c o nti n ue t o be u nreac ha bl e, he/s he will be c o nsi dere d t o ha ve 
wit h dra w n fr o m t he tri al.  
 
 
 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 2 4  of 5 0  
 
 
 
 
 
 
6  
T RI A L D E SI G N  
6. 1  
O ver all Tri al Desi g n  
T his is a ra n d o mize d, d o u ble- bli n d, place b o -c o ntr olle d, 2- wa y cr oss-o ver trial t o e val uate t he 
effect of C 2 1 o n e n d ot helial d ysf u ncti o n a n d safet y i n s u bjects wit h T 2 D M. 
T he s u bjects will ha ve 4 visits at t he trial site:  
•  Visit 1: Scree ni n g will ta ke place wit hi n 3 wee ks of t he pla n ne d first I M P a d mi nistrati o n 
( Da y - 2 1 t o D a y - 1) a n d will i ncl u de t he s u bject’s si g ni n g of t he i nf or me d c o nse nt a n d a n 
eli gi bilit y c hec k.  
•  Visits 2 a n d 3: S u bjects will visit t he trial site f or si n gle - d ose, oral I M P a d mi nistrati o n 
( C 2 1 or place b o acc or di n g t o ra n d o mizati o n list), safet y, t olera bilit y a n d 
p har mac o d y n a mic ( E n d o P A T) assess me nts. T here will be a was h o ut peri o d of 3 t o 1 4 
da ys bet wee n Visits 2 a n d 3. 
•  Visit 4: A fi nal e n d - of-tri al visit will ta ke place 5 t o 1 4 da ys after Visit 3 or after earl y 
wit h dra wal fr o m trial.  
T he d urati o n of t he tri al f or eac h s u bj ect will be  9 t o 4 7 da ys, i ncl u di n g a n u p t o 3-wee k 
scree ni n g p eri o d. 
6. 2  
N u m ber of S u bjects  
T he trial will i ncl u de  1 0 t o 1 4 ra n d o mise d s u bjects , wit h 1 2 bei n g t he tar get n u m ber. 
6. 3  
Tri al Di a gr a m 
 
6. 4  
Tri al D ur ati o n 
Pla n ne d first s u bject scr ee ne d:  
Quarter 2, 2 0 2 3 
Pla n ne d last s u bject ra n d o mise d:  
Q uarter 2, 2 0 2 3  
Pla n ne d last s u bject last visit:   
Quarter 3, 2 0 2 3  
 
T he e n d of trial is defi ne d as t he date of l ast s u bject last visit.  


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 2 5  of 5 0  
 
 
 
 
 
 
6. 5  
Sc he d ule of E ve nts  
Trial pr oce d ures will be perf or me d acc or di n g t o t he fl o w c hart f or trial pr o ce d ures, T a ble 1 , t he 
trial treat me nt i nstr ucti o ns i n Secti o n 7 , a n d t he trial assess me nt s pecifi cati o ns i n Secti o n 8 .  
 
 






 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 2 8  of 5 0  
 
 
 
 
 
 
After c o m plete d dr u g acc o u nta bilit y, all u n use d a n d partl y use d I M P will be ret ur ne d t o s p o ns or 
or s p o ns or’s desig nee f or de str ucti o n or destr u ct e d at t he site acc or di n g t o site pr oce d ures . All 
ret ur ne d I M P will be r ec o ncile d at t he e n d of t h e trial . 
7. 6  
O ver d ose  
A n o ver d ose is a d os e i n e xcess of t he d ose s pecifie d i n t his C T P. 
I n cases of acci de ntal o v er d ose of I M P, sta n dar d s u p p orti ve meas ures will be a d o pte d as 
re q uire d. N o k n o w n a nti d otes a n d/ or s pecifi e d treat me nts  are a vaila ble i n case of o ver d ose wit h 
C 2 1.  
O ver d oses m ust be d oc u me nte d i n t he e C R F. A n o ver d ose wit h ass oci ate d A E will be rec or de d 
as t he A E dia g n osis/s y m pt o ms i n t he A E l o g of t he e C R F. A n o ver d ose wit h o ut ass ociate d 
s y m pt o ms will o nl y be re p orte d i n t he s u bject’s m e dical rec or ds a n d d o c u me nte d i n t he P D l o g. 
7. 7  
Bli n di n g of t he Tri al  
T his is a d o u ble- bli n d trial i n w hic h s u bjects, care pr o vi ders, i n vesti gat ors, o utc o mes assess ors, 
s p o ns or a n d a n y ve n d or staff ar e bli n de d t o I M P all ocati o n i.e., i nter ve nti o n assi g n me nt. The 
all ocati o n of treat me nts will n ot be discl ose d u ntil clea n file has b ee n decl are d a n d t h e data b ase 
has bee n l oc k e d.  
7. 8  
Pr oce d ures f or U n bli n di n g  
T he s p o ns or or s p o ns or’s desi g nee will pr o vi de t h e trial site wit h o ne seale d ra n d o misati o n c o de 
e n vel o pe per eac h r a n d o mise d s u bject. 
I n case of a n e m er ge n c y, t he i n vesti gat or has t he s ole res p o nsi bilit y f or deter mi ni n g if u n bli n di n g 
of a s u bjects’ i nter v e nti o n assi g n me nt is warra nte d. S u bject safet y m ust al wa ys be t he first 
c o nsi derati o n i n ma ki n g s uc h a deter mi nati o n. If t he i n vesti gat or deci d es t hat u n bli n di n g is 
warr a nte d, t he i n vesti gat or s h o ul d ma ke e ver y eff ort t o c o ntact t he s p o ns or pri or t o u n bli n di n g a 
s u bject’s i nter ve nti o n assi g n me nt u nless t his c o ul d dela y e mer g e nc y treat m e nt f or t he s u bject. If 
a s u bject’s i nter v e nti o n assi g n me nt is u n bli n de d, t he s p o ns or m ust be n otifie d wit hi n 2 4 h o urs of 
t his occ urre n ce. T h e date a n d reas o n f or t he u n bli n di n g m ust be rec or de d. 
S p o ns or p har mac o vi gila nce staff or t he p har mac o vi gila nce ve n d or a p p oi nte d b y t he s p o ns or ma y 
u n bli n d t he i nter ve nti o n assi g n me nt f or a n y s u bject wit h a n S A E. If t he S A E re q uires t h at a n 
e x pe dite d re g ul at or y re p ort be se nt t o o ne or m ore re g ulat or y a ge n cies, a c o p y of t he re p ort, 
i de ntif yi n g t he s u bject’s i nter ve nti o n assi g n me nt, ma y be se nt t o t he i n vesti gat or i n acc or da n ce 
wit h l ocal re g ulati o ns a n d/ or s p o ns or p olic y. A bli n di n g pla n will descri be a n y u n bli n de d 
s p o ns or, or ve n d or staff d uri n g t he c o n d uct of t he trial. 
 
 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 2 9  of 5 0  
 
 
 
 
 
 
8  
A S S E S S M E N T S  
T he trial assess me nts ar e descri be d i n t he secti o ns bel o w a n d t he ti mi n g of assess me nts are 
detaile d i n t he fl o w c h art f or trial pr oce d ures (Ta ble 1 ). 
8. 1  
De m o gr a p hics a n d B aseli ne Assess me nts  
8. 1. 1  
I nf or m e d C o nse nt 
Si g ne d i nf or me d c o nse nt m ust be o btai ne d bef ore a n y scree ni n g pr oce d ures are i nitiate d. T he 
i nf or me d c o nse nt pr o ce d ure is f urt her descri be d i n Secti o n 1 5. 2 . 
8. 1. 2  
Eli gi bilit y Criteri a  
Eli gi bilit y criteria s h o ul d be c hec ke d at scree ni n g ( Visit 1) a n d verifie d b ef ore I M P 
a d mi nistrati o n at Visits 2 a n d 3 . T he criteria are s p ecifie d i n Secti o ns 5. 3  a n d 5. 4 . 
8. 1. 3  
De m o gr a p hic I nf or m ati o n 
T he f oll o wi n g de m o gra p hic data will be rec or d e d: ge n der, a g e, et h nicit y, a n d race.  
8. 1. 4  
Hei g ht, Wei g ht, a n d B MI  
Wei g ht a n d hei g ht will be meas ur e d wit h o ut s h oes. B o d y mass i n de x ( B MI) will be cal c ulate d, 
wit h o ne deci mal, fr o m t he rec or de d h ei g ht a n d w ei g ht. 
8. 1. 5  
Me dic al/ S ur gic al Hist or y  a n d C o nc o mit a nt Ill ness  
Me dical/s ur gical hist or y will be o btai ne d b y s u bject i nter vie w t o verif y t h at t he eli gi bilit y criteria 
are met. T h e me dical/s ur gical  hist or y i ncl u di n g date of first dia g n osis of disease u n der trial a n d 
c o nc o mita nt ill nesses will be o btai ne d b y i nter vie wi n g t he s u bject or b y c h ec ki n g his/ her me dical 
rec or ds. 
8. 2  
P h ar m ac o d y n a mic Assess me nts  
8. 2. 1  
E n d o P A T  
T he e n d ot helial vas o dilat or f u ncti o n will be assess e d b y E n d o P A T at visits a n d ti me p oi nts 
s pecifie d i n t he fl o w c hart f or trial pr oce d ures (Ta ble 1 ) acc or di n g t o t he m a n ufact urer’s 
i nstr ucti o ns.  
T he E n d o P A T assess me nt will be c o n d ucte d i n a q uiet, te m perat ure -c o ntr olle d r o o m. Bef ore 
i nitiati n g t he assess me nt, t he s u bject will be s u pi ne f or at least 1 5 mi n utes. T he s u bjects will be 
i nstr ucte d t o re mai n as still as p ossi ble d uri n g t he assess me nt peri o d. E n d o P A T bi o se ns ors will 
be place d o n t h e s u bjects ri g ht a n d left i n de x fi n gers. If t his fi n ger is u ns uita ble ( e. g., fi n ger is 
c ut or i nj ure d), a differe nt fi n ger ma y be use d as l o n g as t he sa me fi n ger is use d o n b ot h ha n ds. 
T he sa me fi n ger s h o ul d prefera bl y be u s e d at all assess me nts. A c uff will be place d o n t he 
n o n d o mi na nt u p per ar m f or occl usi o n of t he brac hi al arter y.  


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 3 0  of 5 0  
 
 
 
 
 
 
Eac h r ec or di n g will c o nsist  of a 5 -mi n ute baseli ne assess me nt, a 5 - mi n ute occl usi o n assess me nt, 
a n d 5- mi n ute p ost- occl usi o n assess me nt. D uri n g p ost- occl usi o n peri o d, bl o o d fl o w is rest ore d 
ca usi n g a n e n d ot heli u m- de pe n de nt vas o dilati o n.  
T he E n d o P A T s oft war e, pr o vi de d wit h t he de vice, will calc ulate t he f oll o wi n g o utc o mes usi n g a 
c o m p uterise d a ut o mate d al g orit h m a n d rec or de d i n t he e C R F:  
•  Reacti v e H y pere mia I n d e x ( R HI) sc ore: p ost- t o- pre occl usi o n p ulse a m plit u de t o n o metr y 
( P A T) si g nal rati o i n t he occl u de d  ar m relati ve t o t he sa me rati o i n t he c o ntr ol ar m, a n d  
c orrecte d f or baseli ne v asc ular t o ne. R HI is a meas ure of e n d ot h elial f u ncti o n.  
•  A u g me ntati o n i n de x ( AI): calc ulate d fr o m P A T p ulses at t he baseli ne peri o d. AI is a 
meas ure me nt of v asc ular  stiff ness a n d reflects t he str uct ural nat ure a n d bas al t o n us of t he 
vessel.  
T he ti me p oi nts of t he i nitiati o n a n d c o m pleti o n of t he E n d o P A T assess me nt, t he fi n gers 
assesse d a n d a n y si g nifica nt de viati o ns fr o m t he i nstr ucti o ns f or use will be rec or de d i n t he 
e C R F. 
8. 3  
S afet y Assess m e nts  
8. 3. 1  
A d verse E ve nts  
A d verse e ve nts ( A Es) will be re p orte d fr o m si g ni n g of i nf or me d c o ns e nt u ntil e n d- of- trial 
partici pati o n ( Visit 4 ).  
At Visits 2 a n d 3, t he s u bjects will be as ke d a b o ut A Es  at a d missi o n t o t he trial site a n d j ust 
bef ore disc h ar g e.  
8. 3. 2  
Pre g n a nc y Test  
W o me n of c hil d beari n g p ote ntial * will u n der g o pre g na nc y t ests ( uri ne di p- stic ks) at all visits. If 
t he uri ne pre g a nc y test is p ositi ve, a bl o o d pre g na nc y test will be perf or me d t o c o nfir m p ositi ve 
pre g na n y. 
* W o me n of n o n -c hil d beari n g p ote ntial are defi ne d as pre-me n o pa usal fe males w h o are sterilise d (t u bal 
li gati o n or per ma ne nt bilateral occl usi o n of fall o pia n t u bes); or p ost- me n o pa usal defi ne d as 1 2 m o nt hs of 
a me n orr hea. 
8. 3. 3  
P h ysic al E x a mi n ati o n 
A p h ysical e xa mi nati o n will be perf or me d b ase d u p o n t he I n vesti gat or’s j u d ge me nt a n d ma y 
i ncl u de t he f oll o wi n g: 
•  Hea d - eyes - ear - n ose-thr o at  
•  Car di o vasc ular s yste m  
•  Res pira t or y s yste m 
•  Ner v o us s yste m 
•  Gastr oi ntesti nal s yste m  
•  M usc ul o- s keletal s yste m 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 3 1  of 5 0  
 
 
 
 
 
 
•  Ur o ge nital s yste m 
•  Der mat ol o g y s yste m 
•  Ot hers, if re q uire d 
As a mi ni m u m , assess me nts of car di o vas c ular s yst e m a n d res pirat or y s yste m m ust be perf or me d 
at V isits 1 a n d 4. 
S y m pt o m- dri ve n p h ysical e xa mi nati o ns will be d o ne u p o n a d missi o n a n d disc har ge fr o m t he 
trial site at Visit 2 a n d 3. A s y m pt o m- dri ve n p h ysical e xa mi nati o n is o nl y warra nte d w he n t h e 
s u bject has pre vi o usl y i n dicate d a n y s y m pt o ms, or w he n t he i n vesti gat or or site n urse has reas o n 
t o belie ve t here m a y be a pr o ble m a n d will o nl y i ncl u de t he affecte d or ga n s yste m or s yste ms. 
A n y a b n or malities will be s pecifie d a n d d oc u me nt e d as cli nicall y si g nifica nt or n ot cli nicall y 
si g nifica nt i n t he e C R F. A b n or mal p ost-I M P ad mi nistrati o n fi n di n gs assesse d b y t he i n vesti gat or 
as cli nicall y si g nifica nt will be re p orte d as A Es.  
8. 3. 4  
Vit al Si g ns  
S yst olic a n d diast olic bl o o d press ure, p ulse a n d b o d y te m perat ure will be meas ure d i n s u pi ne 
p ositi o n after 1 0 mi n utes of rest at visits s pecifie d i n  t he fl o w c hart f or trial pr oce d ures (Ta bl e 1 ). 
At Visits 1, 2 a n d 3, vital si g ns will be meas ure d after I M P a d mi nistrati o n ( a p plica ble f or Visits 
2 a n d 3) a n d b ef or e i nitiati ng t he E n d o P A T assess me nt. 
A n y vital si g ns o utsi de of n or mal ra n g es will be j u d ge d as cli nicall y si g nifica nt or n ot cli nicall y 
si g nifica nt. T he assess me nt will be rec or d e d i n t he e C R F. A b n or mal p ost- I M P a d mi nistrati o n 
fi n di n gs assesse d b y t he i n vesti gat or as cli nicall y si g nifica nt will be re p orte d as A Es. 
8. 3. 5  
Electr oc a r di o gr a m  
A 1 2-lea d E C G will be r ec or de d i n s u pi ne p ositi o n after 1 0 mi n utes of rest at visits s pecifie d i n  
t he fl o w c hart f or trial pr oce d ures (Ta ble 1 ). At visits 2 a n d 3, E C Gs will be rec or de d wit hi n 6 0 
mi n utes p ri or t o I M P d osi n g a n d a gai n pri or t o i nitiati n g t he E n d o P A T assess me nt, 5 0 ± 1 0 
mi n utes after t he I M P d osi n g. T he E C Gs will be re vie we d a n d i nter prete d o n- site b y t he 
i n vesti gat or or desi g nee. 
A n y E C G fi n di n gs o utsi de of n or mal r a n ges will b e s pecifie d a n d d oc u me nt e d as cli nicall y 
si g nificant or n ot cli nicall y si g nifica nt. T he assess me nt a n d t he ti me p oi nt of E C G c ollecti o n  will 
be rec or de d i n t he e C R F. A b n or mal p ost-I M P a d mi nistrati o n fi n di n gs assesse d b y t he 
in vesti gat or as cli nicall y si g nifica nt will be re p ort e d as A Es.  
8. 3. 6  
S afet y L a b or at or y Assess me nts  
Bl o o d sa m ples f or t he a n al ysis of cli nical c he mistr y  a n d hae m at ol o g y para meters will be 
c ollecte d t hr o u g h ve n e p u nct ure a n d a nal yse d b y r o uti ne a nal ytical met h o ds. 
T he safet y  la b orat or y p ar a meters are defi ne d i n Ta ble 4  a n d will be assesse d at visits s pecifie d i n  
t he fl o w c hart f or trial pr oce d ures (Ta ble 1 ). 
A n y la b orat or y v al ues o utsi de of n or mal ra n g es will be s pecifie d a n d d o c u me nte d as a b n or m al 
n ot cli nicall y si g nifica nt, or a b n or mal cli nicall y si g nifica nt i n t he e C R F. A b n or mal val ues 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 3 2  of 5 0  
 
 
 
 
 
 
assesse d b y t he i n vesti gat or as cli nicall y si g nifica nt will be re p orte d as A Es. If a n a b n or mal 
val ue is ass ociate d wit h c orres p o n di n g cli nical si g ns or s y m pt o ms, t he si g n/s y m pt o m s h o ul d be 
re p orte d as t he A E. 
T a ble 4. S afet y l a b or at or y p ar a m eters  
C ate g or y  
P ar a m eter  
Cli nic al c he mistr y  
Ala ni ne a mi n otra nsferase ( A L T)  
Al b u mi n  
Al kali ne p h os p hatase ( A L P)  
As partate a mi n otra nsferase ( A S T)  
Bilir u bi n (t otal a n d c o nj u gate d)  
Calci u m  
Creati ni ne (e G F R i ncl u de d)  
C -reacti ve pr otei n ( CR P ) 
Ga m ma gl uta m yl tra nsferase ( g G T)  
Gl uc ose  
P otassi u m  
S o di u m  
Urea  
H ae m at ol o g y  
Er yt hr oc yte c o u nt  
Le u k oc yte c o u nt wit h differe ntial c o u nt  
Hae mat ocrit ( B -E V F)  
Hae m o gl o bi n ( H b)  
Platelet c o u nt  
F S H  test (at t he scree ni n g 
visit, p ost me n o pa usal fe males 
o nl y)  
F ollicle sti m ulati n g h or m o ne ( F S H)  
e G F R: Esti mate d gl o mer ular filtrati o n rate.  
A n y la b orat or y  a bn or malit y , j u d ge d b y t he i n vesti gat or t o be a cli nicall y rele va nt w orse ni n g 
si nce Visit 1, s h o ul d be re p orte d as A Es if t he la b orat or y a b n or m alit y re q uire d cli nical 
i nter ve nti o n or f urt her i n vesti gati o n, u nless t he la b orat or y a b n or malit y is ass ociate d wit h a n 
alrea d y re p orte d e ve nt.  
8. 4  
Ot her Assess m e nts  
8. 4. 1  
Pri or a n d C o nc o mit a nt M e dic ati o n  
Pri or me dicati o ns ta ke n will be o btai ne d b y s u bject i nter vie w i n or der t o verif y t hat t he eli gi bilit y 
criteria are met . 
A n y use of me dicati o n fr o m scree ni n g u ntil t he e n d- of- trial visit m ust be d oc u me nte d 
a p pr o priatel y i n t he s u bject’s/ patie nt’s e C R F. Rele va nt i nf or mati o n (i.e., na me of me dicati o n, 
d ose, u nit, fre q ue n c y, start a n d st o p dates, reas o n f or use) m ust be rec or d e d. All c ha n ges i n 
me dicati o n s h o ul d be n ote d i n t he e C R F. 
 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 3 3  of 5 0  
 
 
 
 
 
 
9  
A D V E R S E E V E N T S  
9. 1  
A d verse E ve nt D efi niti o ns  
A n a d vers e e ve nt ( A E) is defi ne d as a n y u nt o w ar d me dical occ urre n ce i n a s u bject a d mi nistere d 
t he I M P a n d w hic h ma y or ma y n ot ha v e a ca us al relati o ns hi p wit h t his I M P. A n A E ca n t heref ore 
be a n y u nfa v ora ble a n d u ni nte n de d si g n (e. g. a si g nifica nt a b n or mal la b orat or y fi n di n g, s y m pt o m, 
or dis ease te m p orall y ass ociate d wit h t he use of t h e I M P, w het her or n ot c o nsi dere d relate d t o t he 
I M P. 
A n a d verse dr u g reacti o n ( A D R) is a n y u nt o war d a n d u ni nte n de d res p o nse t o a n I M P assesse d as 
relate d t o a n y d os e a d mi nistere d. Res p o nse mea ns t hat t he A E is assi g ne d a ca us alit y assess me nt 
of “ Relate d ” t o I M P.  
A n A E is c o nsi dere d “ u ne x pecte d ” if t he nat ure, se verit y, or o utc o me is n ot c o nsista nt wit h t he 
refere nce saf et y i nf or mati o n i n t he c urre nt e diti o n of t he I B.  
A Treat me nt E mer g e nt A d verse E ve nt ( T E A E) is  a n y si g n, e ve nt or s y m pt o m t hat e mer ges d uri n g 
treat me nt ha vi n g bee n a bse nt pre-tr eat me nt, or w orse ns relati ve t o t he pre-treat me nt state.  
A Seri o us A d verse E ve nt ( S A E) is a n y u nt o war d me dical occ urre n ce t hat at a n y d ose: 
•  Res ults i n deat h . 
•  Is life-t hr eate ni n g (t his r efers t o a n e ve nt i n w hic h t he s u bject was at ris k of deat h at t he 
ti me of t he e ve nt; it d oes n ot refer t o a n e ve nt t hat h y p ot heticall y mi g ht ha ve ca use d deat h 
if it was m ore se vere.) 
•  Re q uires i n - patie nt h os pitalisati o n or pr ol o n gati o n of e xisti n g h os pitalisati o n*. 
•  Res ults i n persiste nt or si g nifica nt disa bilit y or i nca pacit y . 
•  Is a c o n ge nital a n o mal y or birt h defect. 
Me dical a n d scie ntific j u d ge me nt s h o ul d be e xercise d i n deci di n g w het her e x pe dite d re p orti n g is 
a p pr o priate i n ot her s it uati o ns, s uc h as i m p orta nt m e dical e v e nts t hat ma y n ot be i m me diatel y life-
t hreate ni n g or res ult i n deat h or h os pitalisati o n b ut ma y je o par dise t he s u bject or ma y re q uire 
i nter ve nti o n t o pre ve nt o ne of t he ot h er o utc o mes liste d i n t he defi niti o n a b o ve. T hese s h o ul d als o 
us uall y be c o nsi dere d seri o us. E xa m ples of s uc h e ve nts are i nte nsi ve treat me nt i n a n e mer ge nc y 
r o o m or at h o m e f or aller gic br o nc h os pas m; bl o o d d yscrasias or c o n v ulsi o ns t hat d o n ot res ult i n 
h os pitalisati o n; or de vel o p me nt of dr u g de pe n d e nc y or dr u g a b use. 
* E xe m pti o ns ma y be ma de w he n h os pitalizati o n is d ue t o:  
•  R o uti ne treat me nt or m o nit ori n g of t he i n vesti gate d i n dicati o n, n ot ass oci ate d wit h a n y 
deteri orati o n i n t he c o n diti o n. 
•  Treat me nt t hat was el ecti ve or pre -pla n n e d, f or a pre -e xistin g c o n diti o n t hat is u nrelate d t o 
t he i n dicati o n u n der i n vesti gati o n a n d di d n ot w orse n. 
•  A d missi o n t o a h os pital or ot her i nstit uti o n f or ge neral care, n ot ass ociate d wit h a n y 
deteri orati o n i n t he c o n diti o n. 
9. 2  
Ot her Re p ort a ble I nf or m ati o n  
Certai n i nf or mati o n  alt h o u g h n ot c o nsiste nt wit h a n S A E m ust be rec or d e d, re p orte d, a n d 
f oll o we d u p i n t he sa me wa y as a n S A E. T his i ncl u des: 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 3 4  of 5 0  
 
 
 
 
 
 
•  A n y pre g na n c y t hat occ urs d uri n g trial partici pati o n m ust be re p orte d a n d a d mi nistrati o n 
of I M P m ust be ter mi nate d i m me diatel y. A pre g n a nc y m ust be re p orte d i m me diatel y t o 
s p o ns or or desi g nee. T h e pre g na nc y m ust be f oll o we d u p t o deter mi ne o utc o me i ncl u di n g 
pre mat ure t er mi nati o n a n d stat us of m ot her a n d i nfa nt. T he o utc o me m ust be re p ort e d 
e ve n if t her e ar e n o a b n or mal fi n di n gs. Pre g na nc y c o m plicati o ns a n d electi ve 
ter mi nati ons f or me dical reas o ns m ust be re p orte d as A Es or S A Es, as a p pli ca ble. 
S p o nta ne o us a b orti o n m ust be re p orte d as a n S A E. I n a d diti o n, t he i n vesti gat or m ust 
atte m pt t o c ollect pre g na nc y i nf or mati o n o n a n y fe male part n ers of male trial partici pa nts 
w h o bec o me pre g na nt w hile t he male partici pa nt is e nr olle d i n t he trial. Pre g na nc y 
i nf or mati o n m ust be re p orte d t o s p o ns or as descri b e d a b o ve. 
•  Lactati o n e x p os ur e t o a n d I M P wit h or wit h o ut a n A E. 
•  O ver d ose of a n I M P wit h or wit h o ut a n A E. 
•  I n a d vert e nt or acci de ntal e xp os ure t o a n I M P wit h or wit h o ut a n A E. 
9. 3  
A d verse E ve nt Assess m e nt Defi niti o ns  
9. 3. 1  
Se verit y  
T he i n vesti gat or s h o ul d assess t he se verit y of all A Es acc or di n g t o t he f oll o wi n g defi niti o ns: 
•  Mil d: a ware ness of s y m pt o ms, si g ns, ill ness, or e ve nt t hat is easil y t olerate d.  
•  M o derate: disc o mf ort s ufficie nt t o ca use i nterferen ce  wit h us ual acti vit y. 
•  Se vere: i nca p acit ati n g wit h i na bilit y t o w or k or u n derta ke f urt her n or mal acti vities.  
N ote t he disti ncti o n bet wee n seri o us ness a n d se verit y: T h e ter m se v ere is use d t o descri be t he 
i nte nsit y of t he e ve nt a n d a se ver e e ve nt is n ot necessaril y seri o us. T he seri o us ness criteria ser ve 
as a g ui de f or defi ni n g re g ulat or y re p orti n g o bli gati o ns. 
9. 3. 2  
Rel ati o ns hi p t o I M P 
Assess me nt of ca us alit y is base d o n t he f oll o wi n g c o nsi derati o ns: ass ociati ve c o n necti o ns (ti me 
a n d/ or place), p har m ac ol o gical e x pla nati o ns, pre vi o us k n o wle d ge of t he dr u g, prese nce of 
c haracteristic cli nical or pat h ol o gical p he n o me na, e xcl usi o n of ot her ca uses, a n d/ or a bse n ce of 
alter nati ve e x pl a nati o ns. 
T he i n vesti gat or will assess t he relati o ns hi p t o trial treat me nt f or all A Es a n d S A Es. T he 
relati o ns hi p will be c har acterize d usi n g t he f oll o wi n g ca usalit y rati n gs:  
•  Relate d  
•  N ot relate d  
•  N ot a p plica ble 
Ca usalit y assess me nt i nstr ucti o ns are as f oll o ws: 
Relate d:  T here is a reas o na ble p ossi bilit y t hat t he A E was ca use d b y t he dr u g. T here is a 
reas o na bl e ti me relati o ns hi p t o dr u g i nta ke. T he A E ca n n ot be e x pl ai ne d b y disease or ot her 
dr u gs. T here m a y or ma y n ot be i nf or mati o n a b o ut de- c halle n g e or re-c halle n ge. Disa p peara n ce 


 
 
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of t he A E u p o n de-c halle n ge s u p p orts t his cate g or y. Rea p peara nce u p o n re-c halle n ge is str o n gl y 
s u p p orti ve.  
N ot relate d:  T here is n o r eas o na ble p ossi bilit y t hat t he e ve nt was ca use d b y t he I M P. T h e 
te m p oral relati o ns hi p t o dr u g a d mi nistrati o n ma kes a ca us al relati o ns hi p i m pr o ba ble or ot her 
dr u gs or u n derl yi n g disease or c o n diti o ns pr o vi de pla usi ble e x pla nati o ns.  
N ot a p plica ble:  T his ass ess me nt ca n be use d e. g. i n cases w h ere t he patie nt di d n ot recei ve a n y 
treat me nt wit h I M P. 
9. 3. 3  
O utc o m e  
T he i n vesti gat or will be as ke d t o rec or d t he m ost a p pr o priate o utc o me of t he f oll o wi n g cate g ories: 
•  Rec o ver e d/res ol ve d  
•  Rec o veri n g/res ol vi n g 
•  N ot rec o vere d/ n ot res ol v e d/ o n g oi n g 
•  Rec o ver e d/res ol ve d  wit h se q uelae  
•  
Fatal  
•  
U n k n o w n 
9. 4  
Re c or di n g of A d vers e E ve nts  
All e ve nts meeti n g t he defi niti o n of a n A E m ust be re p orte d i n t he p eri o d fr o m t he s u bject has 
si g ne d t he i nf or me d c o ns e nt f or m u ntil t he e n d- of-trial partici pati o n ( Visit 4 ). 
At eac h visit t he s u bject will be as ke d a b o ut A Es i n a n o bjecti ve ma n ner, e. g.: “ Ha ve y o u 
e x perie n ce d a n y pr o ble ms si nce t he last visit?”. T he y will als o be as ke d if t he y ha ve b ee n 
h os pitalize d, ha d a n y acci de nts, use n a n y ne w me dicati o ns, or c ha n g e d c o n c o mita nt me dicati o n 
re gi me nts ( b ot h prescri pti o n a n d o ver t he c o u nt er me dicati o n). 
O nl y me dicall y q ualifie d pers o n nel ar e all o we d t o assess A Es.  
A Es m ust be re p orte d o n t he A E pa ge of t he e C R F. T he dia g n osis s h o ul d be rec or d e d, if 
a vaila ble. If n o dia g n osis is a vaila ble eac h si g n a n d s y m pt o m s h o ul d be rec or de d as i n di vi d ual 
A Es.  
I nf or mati o n t o be c ollecte d i ncl u des t y pe of e ve nt, ti me of o nset, i n vesti gat or’s assess me nt of 
se verit y a n d r elati o ns hi p t o trial treat me nt, ti me of res ol uti o n of t he e ve nt, s eri o us ness, as w ell as 
a n y re q uir e d treat me nt or e val uati o ns, a n d o utc o m e. T he A Es res ulti n g fr o m c o nc urre nt ill nesses, 
reacti o ns t o c o n c urr e nt ill nesses, reacti o ns t o c o nc urre nt me dicati o ns, or pr o gressi o n of disease 
states m ust als o be re p ort e d. F or f oll o w- u p of A Es please refer t o Secti o n 9. 6 . 
T he Me dical Di cti o nar y f or Re g ulat or y Acti vities ( Me d D R A) will be use d t o c o de all A Es.  
A n y me dical c o n diti o n t hat is prese nt at t he ti me t hat t he s u bject is scree ne d f or t he trial a n d 
w hic h d oes n ot deteri or at e s h o ul d n ot be re p orte d as a n A E. H o w e ver, if t he c o n diti o n 
deteri orat es/ w orse ns at a n y ti me d uri n g t he s u bject’s partici pati o n i n t he trial, it s h o ul d be 
rec or d e d as a n A E. 


 
 
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A b n or mal la b orat or y v al ues s hall be rec or de d as A Es if assesse d as cli nicall y si g nifica n t b y t he 
i n vesti gat or. I n t h at cas e, t he se verit y will be assesse d as per a b o ve. L a b orat or y a b n or malities 
t hat are ass o ciate d wit h a n alrea d y re p orte d m e dical c o n diti o n will n ot be re p orte d as se p arate 
A Es b ut will be use d f or t he assess me nt of t he ass ociate d me dical c o n diti o n (e. g., i ncrease d 
ne utr o p hil c o u nt i n case of a re p orte d i nfecti o n or i ncreas e d gl uc ose i n a p atie nt wit h dia betes).  
C ha n ges i n t he se verit y of a n A E s h o ul d be rec or d e d t o all o w a n assess me nt of t he d urati o n of 
t he e ve nt at eac h le v el of i nte nsit y t o be perf or me d. A n A E c haract erize d as i nter mitte nt re q uires 
d oc u me ntati o n of t he o ns et a n d d urati o n of eac h e pis o de. 
9. 5  
Re p orti n g of Seri o us A d verse E ve nts  
A n y A E w hic h meets t he defi niti o n of a S A Es m ust be re p orte d wit hi n 2 4 h o urs of o btai ni n g 
k n o wle d ge of t he e ve nt. T he i nf or mati o n t o be re p orte d will i ncl u de assess me nt of se verit y, 
ca usal r elati o ns hi p t o I M P or trial pr oce d ures, acti o n ta ke n, o utc o me, a n d a narrati ve d escri pti o n 
of t he c o urse of t he e v e nt.  
T he s p o ns or is res p o nsi ble f or n otif yi n g t he rele va nt Healt h A ut h orities i n c o m plia nce wit h 
a p plica ble le gislati o n. All s us pecte d u ne x pecte d s eri o us a d vers e reacti o ns ( S U S A Rs) are s u bject 
t o e x pe dite d re p orti n g t o Healt h Aut h orities.  
T he i n vesti gat or is res p o nsi ble f or n otif yi n g Et hics C o m mittees ( E Cs) directl y as per E C 
re q uire me nts. 
T he trial s pecific S A E f or m m ust be use d w he n re p orti n g t o t he s p o ns or.  
A d diti o nal i nf or mati o n ma y be s u bse q ue ntl y pr o vi de d. 
T he S A E f or m a n d all ot her rel e va nt d oc u me nts s u p p orti n g t he re p orte d S A E (e. g. dia g n ostic 
pr oce d ur es, h os pital rec or ds, a ut o ps y re p orts) m ust be fa xe d or sca n n e d/e m aile d t o t he s p o ns or 
or s p o ns or’s desi g nee usi n g t he f oll o wi n g e-mail a d dress Vic ore @ pri me vi gila nce.c o m .  
9. 6  
F oll o w- u p o n A d verse E ve nts  
All  A Es  s h o ul d  be  f oll o we d  u ntil  t he y  ha ve  reac h e d  a  fi nal  o utc o me  ( Rec o vere d/res ol ve d;  
Rec o veri n g/res ol vi n g; N ot rec o vere d/ n ot res ol ve d/ o n g oi n g; Rec o vere d/res ol ve d wit h se q uelae; 
Fatal, U n k n o w n) or t he s u bject’s partici pati o n i n t he trial e n ds, w hic h e ver c o mes first. 
S A Es a n d se v ere, n o n -seri o us A Es c o nsi dere d relat e d t o I M P still o n g oi n g after t he tri al e n d s h o ul d 
be f oll o we d o n a re g ular basis acc or di n g t o t he i n vesti gat or’s cli nical j u d g me nt u ntil a f i nal 
o utc o me has b ee n esta blis he d. T he o ut c o me cate g or y “ N ot rec o v ere d/ n ot res ol ve d/ o n g oi n g” ma y 
use d as a fi nal o utc o m e i n sit uati o ns w here t he se verit y gra de is n o l o n ger s u bject t o c ha n ge. 
 
1 0  
C H A N G E S T O T RI A L C O N D U C T  
1 0. 1  
Pr ot oc ol A m e n d m e nts  
Bef ore i m ple me ntati o n of s u bsta ntial c ha n ges (as defi ne d i n E U Cli nical Trials Directi ve 
( 2 0 0 1/ E C/ 2 0)) u nless c o nsi dere d a n Ur ge nt Safet y Meas ure, a p pr o val/fa v o ura ble o pi ni o n m ust 
be o btai ne d fr o m t he a p pr o priate r e g ulat or y a ut h orit y(ies) a n d I E C(s). 


 
 
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Vic ore P h ar m a A B  
Versi o n: 2. 0   
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P a ge 3 7  of 5 0  
 
 
 
 
 
 
1 0. 2  
Pre m at ure Ter mi n ati o n of t he Tri al  
I n case of pre m at ure ter mi nati o n of t he trial, healt h a ut h orities a n d I E Cs will be n otifie d i n 
writi n g, i ncl u di n g t he reas o n f or pre mat ure ter mi n ati o n. 
C o n diti o ns t hat ma y warra nt pre mat ur e ter mi nati o n of t he trial i ncl u de, b ut are n ot li mite d t o t he 
f oll o wi n g: 
•  T he disc o ver y of a n u ne x pecte d a n d si g nifica nt or u nacce pta ble ris k t o t he s u bjects e nr olle d 
i n t he trial. 
•  A decisi o n of t he s p o ns or t o disc o nti n ue de vel o p me nt of t he dr u g. 
1 0. 3  
Pre m at ure Ter mi n ati o n of a Tri al  Sit e 
T he s p o ns or ca n d eci de t o pre mat urel y ter mi nate a site. C o n diti o ns t hat ma y warra nt ter mi nati o n 
i ncl u de, b ut are n ot li mite d t o: 
•  I ns ufficie nt a d h ere n ce t o pr ot oc ol re q uire m e nts. 
•  Fail ure t o e nr ol s u bjects at a n acce pta ble rate . 
 
 
 


 
 
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Versi o n: 2. 0   
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1 1  
D A T A H A N D LI N G A N D R E C O R D K E E PI N G  
1 1. 1  
D at a M a n a ge m e nt 
T he data ma n a ge me nt r o uti nes i ncl u de pr oce d ures f or ha n dli n g of t he e C R F, data b ase set- u p a n d 
ma na ge me nt, data e ntr y a n d verificati o n, data vali dati o n, Q C of t he data bas e, a n d d oc u me nt ati o n 
of t he perf or me d acti vities i ncl u di n g i nf or mati o n of discre pa n cies i n t he pr o cess. T he dat a base, 
data e ntr y scree ns, a n d pr o gra m will be desi g ne d i n acc or d a nce wit h t he C T P. 
Data vali dati o n/ data cl ea ni n g pr oce d ur es are desi g ne d t o ass ure v ali dit y a n d acc urac y of cli nical 
data. T hese pr oce d u res c o nsist of c o m p uterise d o nli ne e dit c hec ks i de ntif yi n g e. g., data val ues 
t hat are o utsi de t he all o we d ra n ge a n d S A S- pr o gra m me d batc h c hec ks o n d ata e x p orts. All trial-
s pecific a n d sta n d ar d d ata vali dati o n pr o gra m mi n g will be teste d pri or t o bei n g use d o n fi nal 
data.  
Detaile d i nf or mati o n o n data ma na g e me nt will be descri be d i n a tri al -s pecific Data M a na ge m e nt 
Pla n ( D M P).  
1 1. 2  
D at a fr o m Cli nic al Tri al Site  
Data fr o m cli nical trial site will be e ntere d i n a n e C R F.  T he e C R F will be a 2 1 C F R part 1 1  
c o m plia nt, pass w or d pr ot ecte d a n d v ali date d s yste m. 
T he in vesti gat or will si g n rele v a nt e C R F secti o ns b y use of a n electr o ni c si g nat ure. O nl y t he 
in vesti gat or  (i.e. , me dicall y  q ualifie d  pers o n nel)  ca n  si g n  data  o n  me dical  assess me nts.  A n y  
c orrecti o ns ma de  b y t he in vesti gat or or a ut h oris e d s taff t o t h e e C R F after ori gi nal e ntr y will be 
d oc u me nt e d i n a n a u dit trail. T he p ers o n ma ki n g t he c ha n g e a n d t he date, ti me a n d reas o n f or t he 
c ha n ge will be i de ntifie d i n t he a u dit trail. C ha n ges t o t he data alrea d y a p pr o ve d/si g ne d b y a n 
in vesti gat or will re q uire re -si g nat ur e b y t he in vesti gat or. T he in vesti gat or ( pri nci pal i n vesti gat or 
or s u b-i n vesti gat or) will si g n all patie nt data i n t he e C R F b y a n electr o nic si g nat ure.  
S u bject  data  will  be  r ec or de d  ps e u d o n y mize d  a n d t he  s u bjects  will  b e  i de ntifie d  o nl y  b y  a  
scree ni n g n u m ber a n d a r a n d o misati o n n u m ber. 
T he  m o nit or  will  c hec k  t he  e C R F  f or  acc urac y  a n d  c o m pleti o n  a n d  perf or m  s o urce  data  
verificati o n. D ata e nte re d i n t he e C R F will be verifie d a gai nst s o urce d ata.  
1 1. 3  
S o urce D at a  
S o urce d oc u me nts c o nt ai ni n g s o urce data pr o vi de e vi de nce f or t he e xiste nce of t he s u bject a n d 
s u bsta ntiate t he i nte grit y of t he data c ollecte d. S o urce d oc u m e nts are file d at t he i n vesti gat or’s 
site. 
A se par ate ori gi n of s o ur ce data list will be ge nerate d bef ore t he start of e nr ol me nt, s pecif yi n g 
t he l ocati o n of t he s o urce of deri ve d i nf or mati o n a p peari n g i n t he e C R F. T his d oc u me nt m ust be 
si g ne d b y t he PI  a n d t he M o nit or t o c o nfir m a gree me nt bef ore start of recr uit me nt. 
S o urce d oc u me nts are all d oc u me nts use d b y t he i n vesti gat or or h os pital t hat relate t o t he 
s u bject’s me dical hist or y, a n d t hat verif y t he e xiste nce of t h e s u bject, t he i n cl usi o n a n d e xcl usi o n 
criteria, a n d all rec or ds c o veri n g t he s u bject’s p artici pati o n i n t he trial. T he y i ncl u de la b orat or y 


 
 
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n otes, me m ora n da, mat erial dis pe nsi n g rec or ds, s u bject files, etc. T h e e C R F ma y c o nstit ute 
s o urce dat a if clearl y defi ne d i n t he ori gi n of s o urce data list.  
T he i n vesti gat or m ust g uara ntee access t o s o urce d oc u me nts t o t he m o nit or, C As a n d t he I E Cs, if 
re q uire d. 
T he m o nit or will perf or m o n g oi n g s o urce data v erificati o n t o c o nfir m t hat data rec or de d i n t he 
eC R F b y a ut h orize d site pers o n nel ar e acc urate, c o m plete, a n d verifi a ble fr o m s o urce 
d oc u me nts; t hat t he safet y a n d ri g hts of s u bjects are bei n g pr otecte d; a n d t h at t he trial is bei n g 
c o n d ucte d i n acc or d a nce wit h t he c urre ntl y a p pr o v e d pr ot oc ol a n d a n y ot h er trial a gree me nts, 
I C H G C P, a n d all a p plica ble re g ulat or y re q uire m e nts.  
T he le vel of s o ur ce d ata verificati o n will be des cri be d i n t he m o nit ori n g pla n. 
1 1. 4  
C o di n g of D at a 
Me dical  hist or y  a n d  A Es  will  be  c o d e d  usi n g  t he  lastest  versi o n  of  M e dical  Dicti o nar y  f or  
Re g ulat or y Acti vities ( Me d D R A ). 
C o nc o mita nt me dicati o n will be c o de d usi n g t h e latest versi o n of W orl d Healt h Or g a nisati o n 
(W H O ) Dr u g Ref ere n ce List.  
1 1. 5  
S u bject C o nfi de nti alit y  
T he c o nfi d e ntialit y of t he s u bject data a n d s u bject rec or ds s hall b e pr otecte d, res pecti n g t he pri vac y 
a n d c o nfi de ntialit y r ules i n acc or d a nce wit h a p plica ble re g ulat or y re q uire me nts. 
 
 
 


 
 
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Vic ore P h ar m a A B  
Versi o n: 2. 0   
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D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 4 0  of 5 0  
 
 
 
 
 
 
1 2  
R E T E N TI O N O F D O C U M E N T S  
T he m o nit or will i nstr uct t he i n vesti gat or t o mai ntai n s o urce d o c u me nts a n d t he si g ne d i nf or me d 
c o nse nt f or m f or eac h s u bject.  
F urt her m ore, t he m o nit or w ill i nstr uct t he i n vesti gat or t o arc hi v e esse ntial d oc u me nts f or t he 
d urati o n defi ne d i n t he I C H G C P R 2  or f or 1 5 years, w hic he v er c o m es first. 
T he s p o ns or will n otif y t he i n vesti gat or w he n rete nti o n of t he trial -relate d rec or ds is n o l o n ger 
re q uire d. 
 
 


 
 
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Versi o n: 2. 0   
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1 3  
S T A TI S TI C A L M E T H O D S  
T he pri nci pal f eat ures of t he statistical a nal ysis  t o be perf or me d are des cri b e d i n t his secti o n. A 
m ore tec h nical a n d detail e d ela b or ati o n of t he pri n ci pal feat ures will be prese nte d i n a se parate 
Statistical A nal ysis Pla n ( S A P), w hic h will be si g ne d a n d a p pr o ve d pri or t o data base l oc k. 
1 3. 1  
Ge ner al  
C o nti n u o us data will be prese nte d i n ter ms of e val ua ble a n d missi n g o bser vati o ns, arit h metic 
mea n, sta n dar d d e viati o n ( S D), me dia n, mi ni m u m,  a n d ma xi m u m val ue.  
Cate g orical data will be prese nte d as c o u nts a n d p erce nt a ges. W h e n a p plica ble, s u m mar y data 
will be pres e nte d b y tr eat me nt, a n d b y assess me nt ti me. I n di vi d ual s u bject d ata will be liste d b y 
s u bject n u m ber, treat me nt a n d, w here a p plica ble, b y assess me nt ti me. 
All descri pti ve s u m maries a n d statistical a nal yses will be perf or me d usi n g S A S Versi o n 9. 4 or 
later ( S A S I nstit ute, I n c., Car y, N C).  
Baseli ne (a part fr o m E n d o P A T assess me nts) will be defi ne d as t he last n o n-missi n g data 
c ollecti o n p oi nt pri or t o t he (firs t) a d mi nistrati o n of I M P. All h y p ot hesis testi n g will use a 
si g nifica nce le v el of 5 %. N o i m p utati o n of missi n g data will be perf or me d. 
1 3. 2  
Deter mi n ati o n of S a m ple Size  
N o f or mal sa m ple size calc ulati o n has bee n perf or me d f or t his trial. T he pr o p ose d sa m ple si ze is 
c o nsi dere d s ufficie nt t o pr o vi de a de q u ate i nf or mati o n t o meet t he trial o bjecti ves. 
1 3. 3  
A n al ysis D at a Sets 
T he S afet y  Set will c o nsist of all s u bjects w h o ha ve bee n ra n d o mise d a n d recei v e d at least o ne 
d ose of I M P. T his a nal ysis set will be use d f or safe t y assess me nts. 
T he P D  A n al ysis Set (P D A S)  will c o nsist of all s u bjects w h o ha ve b ee n ra n d o mise d a n d 
recei v e d at least o ne d ose of I M P, pr o vi de d e val u a ble P D varia bles fr o m eit her Visit 2 or 3, a n d 
w h o ha ve n o A E or pr ot o c ol de viati o ns j u d ge d t o affect t he P D a nal ysis. I n di vi d ual P D val ues 
ma y be e xcl u d e d fr o m t h e a nal ysis as s pecifie d i n t he S A P.    
T he P D R ati o A n al ysis Set ( P D R A S)  will c o nsist of all s u bjects w h o ha ve c o m plete d t he trial 
u p u ntil Visit 3 , pr o vi de d e val ua ble P D varia bles  fr o m b ot h Visits 2 a n d 3, a n d w h o ha ve n o A Es 
or pr ot oc ol de viati o ns j u d ge d t o aff ect t he P D a n al ysis. I n di vi d ual P D val u es ma y be e x cl u de d 
fr o m t he a nal ysis as s pecifie d i n t he S A P.   
1 3. 4  
S u bject Dis p ositi o n  
1 3. 4. 1  
De m o gr a p hics a n d B aseli ne C h ar acteristics  
Descri pti ve statistics f or de m o gra p hics, w ei g ht, hei g ht, a n d B MI will be prese nte d f or all 
s u bjects. All data will be liste d b y s u bject. 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 4 2  of 5 0  
 
 
 
 
 
 
1 3. 4. 2  
Me dic al/s ur gic al  hist or y  
Me dical hist or y will be prese nte d b y s yste m- or ga n -class ( S O C) a n d preferre d ter m ( P T). All data 
will be liste d b y s u bject.  
1 3. 4. 3  
Pri or/c o nc o mit a nt m e dic ati o n  
Pri or/c o nc o mita nt me dicati o ns will be prese nte d b y A T C le vel 4 a n d 5.  All data will be liste d b y 
s u bject. 
1 3. 4. 4  
I M P a d mi nistr ati o n 
All a d mi nistere d i n di vi d ual I M P a d mi nistrati o ns  will be liste d b y s u bject.  
1 3. 5  
P h ar m ac o d y n a mic A n al ysis  
T he E n d o P A T s oft war e, pr o vi de d wit h t he de vice, will calc ulate t he f oll o wi n g o utc o me usi n g a 
c o m p uterise d, a ut o mate d al g orit h m:  
•  Reacti ve H y pere mia I n d e x ( R HI) sc ore: p ost -t o- pre occl usi o n p ulse a m plit u de t o n o metr y 
( P A T) si g nal rati o i n t he occl u de d ar m relati ve t o t he sa me rati o i n t he c o ntr ol ar m, a n d 
c orrecte d f or baseli ne v asc ular t o ne. R HI is a meas ure of e n d ot h elial f u ncti o n. 
•  A u g me ntati o n i n de x ( AI): calc ulate d fr o m P A T p ulses at t he baseli ne peri o d. AI is a 
meas ure me nt of v asc ular stiff ness.  
1 3. 5. 1  
A n al ysis of Pri m ar y E n d p oi nt 
T he per ce nta g e c ha n g e i n t he  pri mar y e n d p oi nt ( R HI) will be c o m pare d b et wee n treat me nts 
usi n g a n a nal ysis of varia nce m o del ( A N O V A) a dj usti n g f or s u bject (ra n d o m), peri o d a n d 
treat me nt. T he a dj uste d mea n differe nce will be prese nte d t o get h er wit h 9 0 % c o nfi de n ce i nter v al 
a n d ass ociated t w o -si de d p-val ue.  
All data will be liste d b y s u bject.  
1 3. 5. 2  
A n al ysis of Sec o n d ar y / E x pl or at or y E n d p oi nt  
T he s ec o n d ar y e n d p oi nt ( AI) will be c o m pare d bet wee n treat me nts usi n g si milar A N O V A m o del  
as f or t he pri mar y e n d p oi nt. 
1 3. 5. 3  
St atistic al/ A n al ytic al Iss ues  
All tests will be t w o -si de d at a 1 0 % si g nifica n ce l e vel.  T here will be n o a dj ust me nt f or m ulti ple 
tests. 
1 3. 5. 3. 1  Missi n g D at a  
T here will be n o i m p utati o n of p har mac o d y na mic or safet y dat a.  


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 4 3  of 5 0  
 
 
 
 
 
 
1 3. 5. 3. 2  E x a mi n ati o n of S u b gr o u ps 
I m p ort a nt de m o gra p hic a n d baseli ne val ue- defi ne d s u b gr o u ps will be e xa mi ne d a n d t he res ults 
prese nte d, e. g., c o m paris o n of eff ects b y a g e, se x a n d baseli ne disease se v erit y  ( T 2 D M). A 
detaile d descri pti o n will be pr o vi de d i n t he S A P . 
 
1 3. 6  
S afet y A n al ysis 
1 3. 6. 1  
A d verse E ve nts  
A n o ver vie w of all treat me nt -e mer gi n g A Es i ncl u di n g se verit y, relati o ns hi p t o I M P, S A Es a n d 
A Es lea di n g t o wit h dra w als of treat me nt a n d wit h dra wal fr o m trial or deat h will be prese nte d . 
T he i nci de nce of treat me nt-e mer gi n g A Es a n d S A Es will be s u m marise d b y s y ste m or ga n class 
(acc or di n g t o Me d D R A) a n d pref err e d ter m (acc or di n g t o Me d D R A) b y treat me nt.  
All treat me nt -e mer ge nt A Es will be liste d  b y s u bject a n d i ncl u de t he v er b ati m ter m e ntere d b y 
t he i n vesti gat or. 
1 3. 6. 2  
Pre g n a nc y  
All pre g na nc y test r es ults will be liste d b y s u bject. 
1 3. 6. 3  
P h ysic al e x a mi n ati o n 
A b n or mal fi n di n gs o n t he p h ysical e xa mi nati o n will be s u m marise d b y visit. 
All p h ysical e xa mi nati o n data will be liste d b y s u bject.  
1 3. 6. 4  
Vit al Si g ns  
Vital si g ns data (e. g., bl o o d press ure a n d b o d y te m perat ure) will be s u m marise d b y visit.  
All vital si g n s data will be liste d b y s u bject. 
1 3. 6. 5  
Electr oc a r di o gr a m  
All E C Gs will be cate g orise d as ” n or mal”, ”a b n or mal, n ot cli nicall y si g nifica nt”, or ”a b n or m al, 
cli nicall y si g nifica nt” (as j u d ge d b y t he i n vesti gat or). T he ass ess me n t will be s u m marise d b y 
visit  a n d ti me p oi nt relati ve t o I M P a d mi nistrati o n.   
All E C G data will be liste d b y s u bject.  
1 3. 6. 6  
L a b or at or y S afet y Assess me nts 
All cli nical la b orat or y val ues o utsi de of n or mal ra n ges will be cate g orise d as ”a b n or m al, n ot 
cli nicall y si g nifica nt”, or ”a b n or mal, cli nicall y si g nifi ca nt” as j u d ge d b y t h e i n vesti gat or.   
All cli nical la b orat or y data ( i.e., val ues o utsi de of n or mal ra n ges a n d cat e g orisati o n) will be 
liste d b y s u bject.  
 
 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 4 4  of 5 0  
 
 
 
 
 
 
1 4  
G O O D C LI NI C A L P R A C TI C E  
T his trial will be carrie d o ut i n c o m plia nce wit h t he pr ot oc ol, c urre nt I C H G C P, sta n dar d 
o perati n g pr oce d ures, t h e E U Cli nical Trials Directi ve  ( 2 0 0 1/ 2 0/ E C), a n d a p plica ble l ocal 
re g ulat or y r e q uire me nts. 
T he i n vesti gat or a gr ees, w he n si g ni n g t his pr ot oc ol, t o a d here t o t he i nstr u cti o ns a n d pr oce d ures 
descri be d i n it, t o t he pri nci ples of t he Declarati o n of Helsi n ki, c urre nt I CH G C P , a n d a p plica ble 
re g ulat or y r e q uire me nts.  
I n c o m plia nce wit h I C H G C P R 2  re q uire me nts, s p o ns or will i de ntif y t h ose pr ocesses a n d data 
t hat are critical t o e ns ure h u ma n s u bject pr otecti o n a n d t he relia bilit y of trial res ults a n d 
f urt her m or e, i de ntif y, e v al uate, c o ntr ol, c o m m u ni cate a n d re vie w ris ks t o t h ose. 
1 5  
E T HI C S  
1 5. 1  
I n depe n de nt Et hics C o m mittees / He alt h A ut h orities  
Bef ore i m ple me nti n g t his trial, t he pr ot oc ol, t he pr o p ose d s u bject i nf or mati o n a n d s u bject 
c o nse nt f or m, a n d ot her d oc u me nts as re q uire d, will be re vie we d b y pr o perl y c o nstit ute d 
I n d e pe n de nt Et hics C o m mittees (I E Cs) a n d b y t he nati o nal re g ulat or y a ut h orities. 
A si g ne d a n d date d stat e me nt t hat t he pr ot oc ol a n d s u bject i nf or mati o n a n d s u bject c o nse nt f or m 
ha ve bee n a p pr o v e d b y t he I E Cs a n d r e g ulat or y a ut h orities will be o btai ne d bef ore tri al i nitiati o n. 
F or eac h i n di vi d ual I E C t he na me a n d o cc u p ati o n of t he c hair m a n a n d t he me m bers of t he I E C 
will be c ollecte d as w ell as a state me nt t hat t he I E C w or ks i n acc or d a nce wit h I C H G C P. 
I E Cs will recei ve u p d ates o n trial pr o gress acc or di n g t o l ocal re g ulati o ns. 
1 5. 2  
I nf or m e d C o nse nt 
T he s u bject’s si g ne d a n d date d i nf or me d c o nse nt t o partici pate i n t he trial will be o btai ne d pri or 
t o a n y trial relate d pr oce d ure bei n g carrie d o ut. 
Bef ore a n y trial relat e d pr oce d ur e t he i n vesti gat or will e x plai n t o t he p ote ntial s u bject t he ai ms, 
met h o ds, reas o na bl y e x p ecte d be n efits a n d p ote ntial hazar ds of t he trial a n d a n y disc o mf ort 
partici pati o n i n t he trial ma y e ntail. S u bjects will be i nf or me d t hat partici pati o n i n t he trial is 
v ol u ntar y a n d t hat t he s u bject ma y wit h dra w fr o m t he trial at a n y ti me a n d f or a n y reas o n. 
S u bjects will be i nf or me d t hat if t he y c h o ose n ot t o partici pate, t his will n ot affect t he care t he 
s u bject will recei v e f or t h e treat me nt of his or h er disease. Fi n all y, s u bjects will be i nf or me d t hat 
t heir rec or ds ma y be accesse d b y healt h a ut h orities a n d a ut h orize d  s p o ns or staff wit h o ut 
vi olati n g t he c o nfi de ntialit y of t he s u bject, t o t he e xte nt p er mitte d b y t he a p plica ble la ws or 
re g ulati o ns. 
All s u bjects will be gi ve n o p p ort u nit y t o as k q uesti o ns a n d will be gi ve n s ufficie nt ti me t o 
c o nsi der bef ore c o nse nti n g. T he s u bjects ma y c h o ose t o be acc o m pa nie d, e. g. b y a fa mil y 
me m ber, d uri n g t he i nf or mati o n pr ocess. After ha vi n g c o nse nte d, a c o p y of t he i nf or me d c o ns e nt 
f or m will be gi ve n t o t he s u bject. 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 4 5  of 5 0  
 
 
 
 
 
 
1 5. 3  
S u bject I nf or m ati o n Car d  
T he s u bject will be pr o vi de d wit h a s u bject i nf or m ati o n car d i ncl u di n g t he f oll o wi n g 
i nf or mati o n:  
•  T hat t he y ar e partici pati n g i n a cli nical trial.  
•  S u bject  trial I D. 
•  T hat t he y ar e treat e d wit h t he I M P.  
•  T he na me a n d p h o n e n u m ber of t he i n vesti gat or. 
•  T he na me a n d a d dr ess of t he s p o ns or. 
1 5. 4  
S u bject Pri v ac y a n d D at a P r otecti o n  
T he i nf or me d c o ns e nt i ncl u des i nf or mati o n t hat d ata will be rec or de d, c ollecte d, a n d pr ocess e d 
a n d i nf or mati o n relat e d t o p ote ntial tra nsfer t o E ur o pea n E c o n o mic Area ( E E A) or n o n- E E A 
c o u ntries. I n acc or d a nce wit h t he Ge neral Data Pr otecti o n Re g ulati o n ( G D P R [ E U] 2 0 1 6/ 6 7 9), 
t hese pse u d o n y mise d dat a will n ot i de ntif y a n y s u bjects ta ki n g part i n t he trial. If a n y p art of t he 
data is ha n dle d b y a n y ot her or ga nisati o n, i nsi de or o utsi de t he E ur o pea n U ni o n, a p pr o priate 
a gree m e nts a n d/ or ot her d oc u me ntati o n will be  esta blis he d, t o e ns ure t hat t he data pr o cessi n g is 
perf or me d i n acc or da n ce wit h t he pr o visi o ns of t he G D P R a n d ot her rel e va nt le gislati o n bef ore 
a n y data tra nsfer t a kes pl ace.  
T he s u bject has t he ri g ht t o re q uest access t o t heir pers o nal data a n d t he ri g ht t o re q uest 
rectificati o n of a n y data t hat is n ot c orrect a n d/ or c o m plete i n acc or d a nce wit h G D P R a n d t he 
re q uest will be rais e d t o t he PI.  
T he in vesti gat or m ust file a s u bject i de ntificati o n list w hic h i ncl u des s ufficie nt i nf or mati o n t o 
li n k rec or ds, i.e., t he e C R F a n d cli nical rec or ds. T his list m ust be preser v e d f or p ossi ble f ut ure 
i ns pecti o ns/a u dits b ut m ust n ot be ma de a vaila ble t o t he s p o ns or e xce pt f or m o nit ori n g or 
a u diti n g p ur p oses. 
Pers o nal data t hat are c ollecte d i n t he trial s uc h as healt h i nf or mati o n a n d et h nicit y are 
c o nsi dere d as se nsiti ve pers o nal data. T his d ata will be pse u d o n y mize d, i.e., pers o nall y 
i de ntifia ble i nf or mati o n ( PII) will be re m o ve d a n d re place d b y a u ni q ue s u bject I D a n d will be 
pr ocesse d b y t h e s p o ns or a n d ot her i n v ol ve d parties d uri n g t he trial. After t he trial e n d, o nl y 
pse u d o n y mize d data ca n be use d, i.e., a g gre gat e d data sets, ca n b e use d. 
F or t his trial, t he s p o ns or is t he data c o ntr oller of all data pr ocesse d d uri n g t he trial (e. g., trial 
master file [ T M F], trial r e p orts) a n d a n y s u bc o ntract ors use d i n t he trial are data pr o cess ors. 
F or d ata t h at ar e pr ocesse d at t he trial site (e. g., me dical rec or ds a n d I S F), t h e site is t he data 
c o ntr oller. 
 
1 6  
A U DI T S A N D I N S P E C TI O N S  
A re pr ese ntati ve of t h e s p o ns or ma y visit t he trial site(s) at a n y ti me d uri n g t he trial or after 
c o m pleti o n of t he trial t o c o n d uct a n a u dit of t he trial. T hese a u dits will re q uire access t o all trial 
rec or ds, i ncl u di n g s o ur ce d oc u me nts, f or i ns pecti o n a n d c o m paris o n wit h t h e eC R Fs. T h e 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 4 6  of 5 0  
 
 
 
 
 
 
i n vesti gat or a n d ot her tri al pers o n nel will be res p o nsi ble f or bei n g pres e nt a n d a vaila ble f or 
c o ns ultati o n d uri n g r o uti nel y sc he d ule d site a u dit visits c o n d ucte d b y t he s p o ns or ’s 
re pres e ntati ve. 
Si milar a u diti n g pr oce d ures (i ns pecti o ns) ma y als o be c o n d ucte d b y a ge nts of re g ulat or y h ealt h 
a ut h orities, eit her as p art of a nati o nal G C P c o m plia nce pr o gra m or t o re vie w t he res ults of t his 
trial i n s u p p ort of a re g ul at or y s u b missi o n. T he i n vesti gat or s h o ul d n otif y t he s p o ns or’s 
re pres e ntati ve or s p o ns or i m me diatel y, if he/s he has bee n c o nt acte d b y a re g ulat or y a ge nc y 
c o ncer ni n g a n u pc o mi n g i ns pecti o n.  
 
1 7  
M O NI T O RI N G  
M o nit ori n g will be c o n d ucte d b y a s p o ns or re prese ntati ve. Bef ore trial i nitiati o n t he m o nit or will 
re vie w t he pr ot oc ol a n d t he eC R F wit h t he i n vesti g at or(s) a n d t h eir trial pers o n nel.  
As descri be d i n t he m o nit ori n g pla n, t he m o nit or will peri o dicall y visit t he trial site t o c hec k t he 
c o m plete ness of s u bject r ec or ds, t he acc urac y of e ntries i n e C R Fs, t he a d here nce t o t he pr ot oc ol 
a n d t o G C P, t he pr o gress of e nr ol me nt a n d t he h a n dli n g a n d acc o u nti n g of I M P. Ke y trial 
pers o n nel m ust be a vaila ble t o assist t he m o nit or d uri n g t hese visits.  
T he i n vesti gat or m ust gi ve t he m o nit or direct access t o s o urce dat a/ d oc u m e nts (e. g. rel e va nt 
h os pital or me dical rec or ds) t o c o nfir m t heir c o nsiste nc y wit h t he e ntries i n e C R Fs. N o 
i nf or mati o n i n t hese rec or ds a b o ut t he i de ntit y of t he s u bjects m ust lea ve t h e trial site. 
 
1 8  
R E P O R TI N G O F R E S U L T S  
1 8. 1  
Cli nic al Tri al Re p ort  
Data will be re p orte d i n  a n i nte grate d cli nical trial re p ort i n c o m plia nce wit h t he re q uire m e nts of 
t he c urr e nt versi o n of I C H E 3: Str uct ure a n d C o nt e nt of Cli nical St u d y Re p ort. T he si g nat or y 
i n vesti gat or will re vie w a n d si g n t he i nte grate d cli nical trial re p ort. 
1 8. 2  
Use of I nf or m ati o n 
All u n p u bli s he d i nf or mati o n relati n g t o t his trial a n d/ or t o t he trial dr u g is c o nsi dere d 
c o nfi de ntial b y t he s p o ns or a n d s hall re mai n t he s ole pr o pert y of t he s p o ns or. 
T he i n vesti gat or m ust acc e pt t hat t he s p o ns or ma y use t he i nf or mati o n fr o m t his cli nical trial i n 
c o n necti o n wit h t he de v el o p me nt of t he I M P, a n d t heref ore, ma y discl ose it as re q uire d t o ot her 
i n vesti gat ors, t o g o ver n me nt lice nsi n g a ut h orities, t o re g ulat or y a g e ncies of ot her g o ver n me nts, 
st oc k e xc ha n g e mar k et, a n d c o m mercial part ners. 
1 8. 3  
P u blic ati o n of Res ults  
T he s p o ns or is c o m mitte d t o p u blis hi n g t he trial res ults, w het her p ositi ve or ne gati ve, i n a p eer-
re vie we d j o ur nal. 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 4 7  of 5 0  
 
 
 
 
 
 
T he criteri a f or a ut h ors hi p as set o ut b y t he C o m mittee of Me dical J o ur n al E dit ors 
(w w w.ic mje. or g ) will be a p plie d (Wa g er  et al., 2 0 0 3; Graf et al., 2 0 0 9). 
T he c o ntri b ut ors hi p m o del will be a p plie d a n d c o ntri b ut ors w h o d o n ot meet t he criteria f or 
a ut h ors hi p will be liste d i n a n ac k n o wl e d g me nts secti o n wit h descri pti o ns of t he r ole of eac h 
c o ntri b ut or i n or der t o e ns ure i n de xati o n i n t he Nati o nal Li brar y of Me dici n e. 
P u blicati o ns are s u bject t o t he f oll o wi n g c o n diti o ns: 
•  Data ar e t he pr o p ert y of t he s p o ns or a n d ca n n ot be p u blis he d wit h o ut pri or a ut h orizati o n 
fr o m t he s p o ns or. 
•  P u blicati o ns s h o ul d be drafte d wit h pr otecti o n of i n di vi d ual pri vac y, i ntellect ual pr o pert y a n d 
c o ntract ri g hts i n mi n d, a n d als o c o nf or m t o le gislati o n a n d c urre nt nati o nal practices i n 
pate nt a n d ot her la ws. 
•  T he pri mar y p u blicati o n ( i.e. t he res ults fr o m all ce nters) s h o ul d be p u blis h e d bef ore, or i n 
parallel wit h, a n y sec o n d ar y p u blicati o ns.  
•  P u blicati o ns s hall n ot discl ose a n y s p o ns or c o nfi d e ntial i nf or mati o n or pr o pert y. 
 
1 9  
I N S U R A N C E A N D LI A BI LI T Y 
T he s p o ns or has s u bscri b e d t o a n i ns ura nce p olic y c o veri n g, i n its ter ms a n d pr o visi o n, its le gal 
lia bilit y f or i nj uries ca use d t o partici pati n g s u bjects a n d arisi n g o ut of trial pr oce d ures perf or me d 
i n acc or d a nce t his pr ot oc ol, i n acc or da n ce wit h a p plica ble la w a n d wit h I C H G C P R 2 . 
 
 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
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2 0  
R E F E R E N C E S  
Graf, C., Battista, W. P., Bri d ges, D., Br uce- Wi n kler, V., C o nat y, J. M., Ellis o n, J. M., Fiel d, E. 
A., G urr, J. A., M ar x, M. E., Patel, M., Sa nes- Miller, C., Yar k er, Y. E. I nter nati o nal S ociet y f or 
Me dical P u blicati o n Pr ofessi o nal. 2 0 0 9 G o o d p u blicati o n practice f or c o m m u nit y c o m pa n y 
S p o ns ore d me dical res earc h: t he G P P 2 g ui deli nes. B MJ 3 3 9: b 4 3 3 0. 
I C H H ar m o nize d Tri partite G ui deli ne E 3. 1 9 9 5 Str uct ure a n d C o nte nt of Cli nical St u d y Re p orts. 
Ste p 5. 
I C H H ar m o nize d Tri partite G ui deli ne E 6 ( R 2). 1 9 9 7 Ste p 5: G ui deli ne f or G o o d Cli nical 
Practice. A d o pte d b y C P M P Dec 2 0 1 6. 
Matr o u g ui, K., L o ufr a ni, L. , He y mes, C., Le v y, B. I., a n d He nri o n, D. 1 9 9 9 Acti vati o n of A T( 2) 
rece pt ors b y e n d o ge n o us a n gi ote nsi n II is i n v ol ve d i n fl o w-i n d uce d dilati o n i n rat resista nce 
arteries. H y p erte nsi o n 3 4: 6 5 9 – 6 6 5. 
Stec keli n g s, U. M., Wi d d o p, R. E., St urr oc k, E. D., L u b be, L., H ussai n, T., Kasc hi na , E., U n g er, 
T., Hall ber g , A., Care y, R. M., a n d S u m ners, C. 2 0 2 2 T he a n gi ote nsi n A T 2 rece pt or: fr o m a 
bi n di n g site t o a n o vel t hera pe utic t ar get. P har m ac ol . Re v . 7 4: 1 0 5 1 – 1 1 3 5. 
Wa ger, E., Fiel d, E. A., Gr oss ma n, L. 2 0 0 3 G o o d p u blicati o n practices f or p har mace utical 
c o m pa nies: w h y we n ee d a n ot her set of g ui deli nes. C urr. Me d. Res. O pi n. 1 9( 3): 1 4 7- 8. 
 
 
 


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 4 9  of 5 0  
 
 
 
 
 
 
2 1  
A B B R E VI A TI O N S  
A b bre vi ati o n   
E x pl a n ati o n  
A D R  
A d verse Dr u g Reacti o n  
A E  
A d verse E ve nt  
AI  
A u g me ntati o n In de x  
A L P  
Al kali ne P h os p hatase  
A L T  
Ala ni ne A mi n otra nsferase  
A N C  
A bs ol ute N e utr o p hil C o u nt  
A N O V A  
A nal ysis of Varia nce  
A R B  
A n gi ote nsi n R ece pt or B l oc ker 
A S T  
As partate A mi n otra nsferase  
A T 1 R  
A n gi ote nsi n II T y pe  1 R ece pt or 
A T 2 R  
A n gi ote nsi n II T y pe  2 R ece pt or 
A T C  
A nat o mical T hera pe utic C he mical  
A T R A G  
A n gi ote nsi n II T y pe 2 R ece pt or A g o nist  
A U C  
Area U n der  t he C ur ve  
A V  
Atri o ve ntric ular  
BI D  
T wice dail y (lat. bis i n die ) 
B MI  
B o d y Mass I n de x  
B C R P  
Breast ca ncer resista nce pr otei n  
B U N  
Bl o o d Urea Nitr o ge n  
C 2 1  
C o m p o u n d 2 1  
C ma x  
Ma xi m u m plas ma c o nce ntrati o n  
C O VI D -1 9  
C or o na vi r us D isease 2 0 1 9 
C N S  
Ce ntral Ner v o us S yste m  
C R F  
Case Re p ort F or m  
C R P  
C -reacti ve pr otei n 
C T C A E  
C o m m o n ter mi n ol o g y criteria f or a d verse e ve nts  
C T P  
C li nical Trial  Pr ot oc ol  
C T R  
C li nical Trial  R e p ort 
C V  
C oefficie nt of V ariati o n 
C Y P  
C yt oc hr o me P 4 5 0 e nz y mes  
D DI  
Dr u g -D r u g I nteracti o ns 
e C R F  
electr o nic Case Re p ort F or m  
E C G  
Electr ocar di o gra p h y  
E o T  
E n d of Treat me nt  
E M A  
E ur o pea n Me dici nes A ge nc y  
e N O S  
E n d ot helial nitric o xi de s y nt hase  
E R A  
E n d ot heli n rece pt or a nta g o nist  
E U  
E ur o pea n U ni o n  
F S H  
F ollicle -sti m ulati n g H or m o ne  
F U  
F oll o w -u p  
G C P  
G o o d Cli nical Practice  
g G T  
Ga m ma Gl uta m yl Tra nsferase  
G L P -1  
Gl uca g o n -L i ke P e pti de-1  
G M P  
G o o d Ma n ufact uri n g Practise  
H b  
Hae m o gl o bi n  
H Bs A g  
He patitis B vir us s -A nti ge n   
H C G  
H u ma n C h ori o nic G o na d otr o pi n  
H C V A b  
He patitis C vir us a nti b o dies  


 
 
Cli nic al Tri al Pr ot oc ol  
 
Vic ore P h ar m a A B  
Versi o n: 2. 0   
Tri al I D: V P-C 2 1 -0 1 3  
D ate: 0 3 -M A R -2 0 2 3  
 
 
C o nfi de nti al  
P a ge 5 0  of 5 0  
 
 
 
 
 
 
HI V  
H u ma n I m m u n o deficie nc y Vir us  
H D L  
Hi g h -de nsit y Li p o pr otei n  
hs -C R P  
h i g h-se nsiti vit y C-Reacti ve Pr otei n  
I B 
I n vesti gat or’s Br oc h ure 
I C H 
I nter nati o nal C o nfere nce o n Har m o nizati o n 
I E C 
I n de pe n de nt Et hics C o m mittee 
I M P 
I n vesti gati o nal Me dici nal Pr o d uct 
I P F 
I di o pat hic P ul m o nar y Fi br osis 
I U D 
I ntra uteri ne de vice  
I U S 
I ntra uteri ne h or m o ne-releasi n g s yste m 
L D  
Lactate de h y dr o ge nase  
L D L  
L o w -de nsit y Li p o pr otei n  
L F T  
Li ver F u ncti o n Test  
M D R 1  
M ulti -Dr u g Resista nce Pr otei n  1  
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
N O  
Nitric o xi de  
N O A E L  
N o O bser ve d A d verse Effect Le vel  
P D  
P har mac o d y na mic  
P K  
P har mac o ki netic  
P P A R Ɣ  
P er o xis o me P r oliferat or-A cti vate d R ece pt or -ga m ma  
O A T 3  
Or ga nic A ni o n T ra ns p orter 3 
O A T P 1 B 1  
Or ga nic A ni o n T ra ns p orti n g P ol y pe pti de 1 B  
Q Tc F  
Q T i nter val wit h Fri dericia's  c orrecti o n 
R A S  
Re ni n -A n gi ote nsi n S yste m  
R HI  
Reacti ve H y pere mia In de x  
R P  
Ra y na u d’s P he n o me n o n  
S A E  
Seri o us A d verse E ve nt  
S A P  
Statistical A nal ysis P la n 
S A S  
Safet y A nal ysis Set  
S L C  
S ol ute Car rier 
S Sc  
S yste mic Scler osis  
S O P  
Sta n dar d O perati n g Pr oce d ure  
S U S A R  
S us pecte d U ne x pecte d Seri o us A d verse Reacti o n  
T 2 D M  
T y pe 2 Dia betes Mellit us  
T S H  
T h yr oi d Sti m ulati n g H or m o ne  
W H O  
W orl d Healt h Or ga nizati o n  
W H O D r u g 
W H O Dr u g Dicti o nar y  
W O C B P  
W o me n of C hil d beari n g P ote ntial