An Open-Label, Randomised, Controlled, Parallel-Design, Multicentre, Phase IV Study of Sodium Zirconium Cyclosilicate and Enhanced Nutrition Advice Compared to Standard of Care in Dialysis Patients With Hyperkalaemia (GRAZE)
Phase: PHASE4
Conditions: Hyperkalaemia
Sponsor: AstraZeneca

D oc u me nt T y pe:  
D oc u me nt Dat es: 
St u d y Title: 
Fi nal Pr ot oc ol  
D 9 4 8 0 C 0 0 0 1 4 Pr ot oc ol Versi o n 3. 0 ( 1 2 A u g ust 2 0 2 1) 
A n  O pe n- La bel, Ra n d o mise d, C o ntr olle d, Parallel- Desi g n, 
M ultice ntre, P hase I V St u d y of S o di u m Zirc o ni u m C ycl osilicate a n d 
E n ha nce d N utriti o n A d vice C o m pare d t o Sta n dar d of Care i n 
Dial ysis P atie nts wit h Hy per kalae mia  ( GR A Z E) 
Pr ot oc ol Refere nce  N u m ber: D 9 4 8 0 C 0 0 0 1 4 
N C T N u m ber:    
N C T 0 4 9 9 7 1 6 1 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y   
1 of 8 2  
 
 
Cli nic al St u d y Pr ot oc ol   
 
St u d y I nter ve nti o n  S o di u m zirc o ni u m c ycl osilicate  
 
St u d y C o de  
D 9 4 8 0 C 0 0 0 1 4  
 
Ve r s i o n  
3. 0  
 
Date  
1 2  A u g 2 0 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A n O pe n -L a bel, R a n d o mi se d, C o ntr olle d, P ar allel -Desi g n, 
M ultice ntre, P h ase I V St u d y of S o di u m Zirc o ni u m C ycl osilic ate  
a n d E n h a nce d N utriti o n A d vice C o m p are d t o St a n d ar d of C are i n 
Di al ysis P atie nts wit h H y per k al ae mi a ( G R A Z E)  
 
S p o ns or N a me: Astra Ze neca  A B  
Le g al Re gistere d A d dress : 1 5 1 8 5 S ö dertälje, S we de n  
Re g ul at or y A ge nc y I de ntifier N u m ber(s) : U S I N D : 1 0 8 9 5 1 / E u dra C T: 2 0 2 1 - 0 0 0 4 5 7- 8 1  
T his Cli nical St u d y Pr ot oc ol has bee n s u bject t o a peer re vie w acc or di n g t o Astra Ze neca 
sta n dar d pr oce d ures. T he Cli nical St u d y Pr ot oc ol is p u blicl y re gistere d a n d t he res ults are 
discl ose d a n d/ or p u blis he d acc or di n g t o t he Astra Ze neca Gl o bal P olic y o n Bi oet hics a n d i n 
c o m plia nce wit h pre vaili n g la ws a n d re g ulati o ns. 
Pr ot oc ol N u m ber:  3. 0 
St u d y I nter ve nti o n : S o di u m zirc o ni u m c ycl osilicate ( S Z C); bra n d n a me L O K E L M A ®  
St u d y P h ase:  4 
S h ort Title:  S o di u m Zirc o ni u m C ycl osilicate  a n d E n ha nce d N utriti o n St u d y 
St u d y p h ysici a n a n d i n vesti g at or n a mes a n d c o nt act I nf or m ati o n will be pr o vi de d 
se p ar atel y. 
 
Redacted for Public Disclosure

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y   
2 of 8 2  
P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S T A B L E  
 
D O C U M E N T HI S T O R Y  
D oc u me nt  
D ate  
A me n d me nt, C S P Versi o n 3. 0  
1 2 -A u g -2 0 2 1  
A me n d me nt , C S P V ersi o n 2. 0  
0 5 -Ma y -2 0 2 1  
C S P V ersi o n 1. 0 
1 6 - Mar-2 0 2 1  
 
A me n d me nt 2 1 2- A u g ust - 2 0 2 1 
T his a me n d me nt is c o nsi dere d t o be n o n -s u bsta ntial base d o n t he criteria set f ort h i n Article 1 0(a) of 
Directi ve 2 0 0 1/ 2 0/ E C of t he E ur o pea n Parlia me nt a n d t he C o u ncil of t he E ur o pea n U ni o n beca use it 
neit her si g nifica ntl y i m pacts t he safet y or p h ysical/ me ntal i nte grit y of partici pa nts n or t he scie ntific 
val ue of t he st u d y.  
O ver all R ati o n ale f or t he A me n d me nt:
Secti o n # a n d 
N a me  
Descri pti o n of C h a n ge  
Brief R ati o n ale  
S u bst a nti al/ N o n -s u bst a nti al 
Secti o n 5. 1 
I ncl usi o n 
Criteria  
Clarificati o ns o n t he birt h 
c o ntr ol met h o ds all o we d f or 
fe male partici pa nts of 
c hil d beari n g p ote ntial  
e nr olle d i n t he U nite d -
Ki n g d o m  
Me dici nes a n d 
healt hcare pr o d uct 
Re g ulat or y A ge nc y 
re q uest 
N o n -s u bsta ntial 
Secti o n 9. 3 
P o p ulati o ns f or 
A nal yses  a n d 
A p pe n di x A  3 
Clarificati o n o n scree ni n g 
p hase  defi niti o n  
T o all o w f or partici pa nts 
w h o are n ot c o nse nte d 
o n a LI DI da y t o still be 
eli gi ble 
N o n -s u bsta ntial 
Secti o n 1. 3 
Sc he d ule of 
Acti vities  a n d 
A p pe n di x A 3 
F urt her t o t he c ha n ge i n 
scree ni n g p hase  defi niti o n, 
t he date of o btai ni n g t he I C F 
has bee n clarifie d  
I C F ca n be o btai ne d u p 
t o 7 da ys pri or t o st u d y 
s pecific assess me nts 
N o n -s u bsta ntial 
Secti o n 9. 4. 3. 2 
Sec o n dar y 
E n d p oi nts  
Mi n or e dit orial re visi o ns  o n 
t he statistical testi n g 
state me nt f or t he n o n-
i nferi orit y test  
T y p os, t heref ore ha ve 
n ot bee n s u m marise d  
N o n -s u bsta ntial 
Secti o n 9. 4. 3. 2 
Sec o n dar y 
E n d p oi nts  
U p date i n t he c o n diti o n t o 
reject t he n ull h y p ot hesis 
T he c o n diti o n t o reject 
t he n ull h y p ot hesis needs 
t o matc h wit h t he 
c orrecte d statistical 
testi n g state me nt f or t he 
n o n -i nferi orit y test 
N o n -s u bsta ntial 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y   
3 of 8 2  
Secti o n # a n d 
N a me  
Descri pti o n of C h a n ge  
Brief R ati o n ale  
S u bst a nti al/ N o n -s u bst a nti al 
A p pe n di x C  3 
A b bre viate d 
Treat me nt 
Satisfacti o n 
Q uesti o n naire 
f or Me dicati o n 
T S Q M - 9 
Deleti o n of si de -effects i n t he 
i nstr ucti o n te xt 
T o clarif y t hat 
partici pa nts are n ot 
re q ueste d t o assess si de-
effects i n t his versi o n of 
t he T S Q M 
N o n -s u bsta ntial 
T hr o u g h o ut  
Mi n or e dit orial a n d d oc u me nt 
f or matti n g re visi o ns 
Mi n or, t heref ore ha ve 
n ot bee n s u m marise d  
N o n -s u bsta ntial 
 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y   
4 of 8 2  
T A B L E O F C O N T E N T S  
TI T L E P A G E  ............................................................................................................................. 1 
P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S T A B L E  ....................................... 2 
T A B L E O F C O N T E N T S  ........................................................................................................... 4 
1  
P R O T O C O L S U M M A R Y  ...................................................................................... 8 
1. 1  
S y n o psis .................................................................................................................. 8  
1. 2  
Sc he ma  .................................................................................................................. 1 1  
1. 3  
Sc he d ule of Acti vi ties ........................................................................................... 1 1  
2  
I N T R O D U C TI O N ................................................................................................ 1 5 
2. 1  
St u d y Rati o nale ..................................................................................................... 1 5  
2. 2  
Bac k gr o u n d ........................................................................................................... 1 5  
2. 3  
Be nefit/ Ris k Assess me nt  ...................................................................................... 1 6 
3  
O BJ E C TI V E S A N D E N D P OI N T S  ...................................................................... 1 7 
3. 1  
Esti ma n ds f or Pri mar y O bjecti ve  ......................................................................... 1 9 
4  
S T U D Y D E SI G N  ................................................................................................. 2 0 
4. 1  
O verall Desi g n  ...................................................................................................... 2 0 
4. 1. 1  
St u d y C o n d uct Miti gati o n D uri n g St u d y Disr u pti o ns D ue t o Cases of Ci vil 
Cr isis, Nat ural Disaster, or P u blic Healt h Crisis .................................................. 2 0 
4. 1. 2  
U p t o 1- m o nt h H K Treat me nt P hase (all partici pa nts)  ......................................... 2 0 
4. 1. 3  
4- m o nt h Diet C o m paris o n P hase ( 2 ar ms) ........................................................... 2 1  
4. 1. 4  
F oll o w- u p P hase (all partici pa nts)  ........................................................................ 2 1 
4. 2  
Scie ntific Rati o nale f or St u d y Desi g n  .................................................................. 2 1 
4. 3  
J ustificati o n f or D ose ............................................................................................ 2 1 
4. 4  
E n d of St u d y Defi niti o n ........................................................................................ 2 2  
5  
S T U D Y P O P U L A TI O N  ....................................................................................... 2 2 
5. 1  
I ncl usi o n Criteria .................................................................................................. 2 2 
5. 2  
E xcl us i o n Criteria ................................................................................................. 2 3 
5. 3  
Lifest yle C o nsi derati o ns  ....................................................................................... 2 5 
5. 4  
Scree n Fail ures  ..................................................................................................... 2 5 
6  
S T U D Y I N T E R V E N TI O N  ................................................................................... 2 5 
6. 1  
St u d y I nter ve nti o n(s) A d mi nistere d  ...................................................................... 2 5 
6. 1. 1  
I n vesti gati o nal Pr o d ucts ....................................................................................... 2 5 
6. 1. 2  
S o C Dietar y A d vice  .............................................................................................. 2 6 
6. 1. 3  
E n ha nce d Dietar y A d vice  ..................................................................................... 2 6 
6. 1. 4  
Diet M o bile A p p ( N o o m) ..................................................................................... 2 6  
6. 2  
Pre parati o n/ Ha n dli n g/ St ora ge/ Acc o u nta bilit y  ...................................................... 2 7 
6. 3  
Meas ures t o Mi ni mise Bias: Ra n d o misati o n a n d Bli n di n g  .................................. 2 7 
6. 4  
St u d y I nter ve nti o n C o m plia nce ............................................................................ 2 7  

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y   
5 of 8 2  
6. 5  
C o nc o mita nt T hera p y  ........................................................................................... 2 8 
6. 5. 1  
Resc ue Me dici ne  ................................................................................................... 2 9 
6. 5. 2  
Dial ys ate P otassi u m C o nce ntrati o n Prescri pti o n  .................................................. 2 9 
6. 6  
D ose M o dificati o n  ................................................................................................ 3 0 
6. 7  
I nter ve nti o n After t he E n d of t he St u d y ................................................................ 3 0 
7  
DI S C O N TI N U A TI O N  O F  S T U D Y I N T E R V E N TI O N  A N D  P A R TI CI P A N T  
DI S C O N TI N U A TI O N/ WI T H D R A W A L  ............................................................. 3 0 
7. 1  
Disc o nti n uati o n of St u d y I nter ve nti o n ................................................................. 3 0  
7. 1. 1  
Te m p orar y Disc o nti n uati o n .................................................................................. 3 1  
7. 2  
Partici pa nt Wit h dra wal fr o m t he St u d y  ................................................................ 3 1 
7. 3  
L ost t o F oll o w- u p ................................................................................................. 3 2  
8  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  ................................................ 3 2 
8. 1  
Efficac y Assess me nts  ............................................................................................ 3 3 
8. 1. 1  
P otassi u m  .............................................................................................................. 3 3 
8. 1. 2  
Patie nt -Re p orte d O utc o mes ( P R Os)  ..................................................................... 3 3 
8. 1. 2. 1  
K D Q O L ™- 3 6 ....................................................................................................... 3 3  
8. 1. 2. 2  
E Q - 5 D- 5 L ............................................................................................................. 3 3 
8. 1. 2. 3  
T S Q M - 9 ................................................................................................................ 3 3 
8. 1. 2. 4  
P GI C  ..................................................................................................................... 3 4 
8. 1. 2. 5  
A d mi nistrati o n of Electr o nic Patie nt -Re p orte d O utc o mes (e P R Os)  .................... 3 4 
8. 2  
Safet y Assess me nts  ............................................................................................... 3 5 
8. 2. 1  
P h ysical E xa mi nati o ns  .......................................................................................... 3 5 
8. 2. 2  
Vital Si g ns  ............................................................................................................. 3 5 
8. 2. 3  
Electr ocar di o gra ms  ............................................................................................... 3 5 
8. 2. 4  
Cli nical Safet y La b orat or y Assess me nts  .............................................................. 3 6 
8. 2. 5  
Ot her Assess me nts  ................................................................................................ 3 7 
8. 2. 5. 1  
Dial ysis Prescri pti o n  ............................................................................................. 3 7 
8. 2. 5. 2  
Dial ysis A de q uac y  ................................................................................................ 3 7 
8. 2. 5. 3  
I nter dial ytic Wei g ht Gai n (I D W G) ....................................................................... 3 7 
8. 3  
A d verse E ve nts a n d Seri o us A d verse E ve nts ....................................................... 3 7  
8. 3. 1  
Ti me Peri o d a n d Fre q ue nc y f or C ollecti n g A E a n d S A E I nf or mati o n  ................. 3 7 
8. 3. 2  
F oll o w- u p of A Es a n d S A Es ................................................................................. 3 8  
8. 3. 3  
Ca usalit y C ollecti o n  ............................................................................................. 3 9 
8. 3. 4  
A d verse E ve nts Base d o n Si g ns a n d S y m pt o ms .................................................. 3 9  
8. 3. 5  
A d verse E ve nts Base d o n E xa mi nati o ns a n d Tests  .............................................. 3 9 
8. 3. 6  
Re p orti n g of Seri o us A d verse E ve nts ................................................................... 4 0  
8. 3. 7  
Pre g na nc y ............................................................................................................. 4 0  
8. 3. 7. 1  
Mater nal E x p os ure ................................................................................................ 4 1  
8. 3. 7. 2  
Pater nal E x p os ure ................................................................................................. 4 1  
8. 3. 8  
Me dicati o n Err or  ................................................................................................... 4 2 
8. 4  
O ver d ose ............................................................................................................... 4 2  
8. 5  
H u ma n Bi ol o gical Sa m ples  .................................................................................. 4 2 
8. 6  
H u ma n Bi ol o gical Sa m ple Bi o mar kers  ................................................................ 4 3 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y   
6 of 8 2  
8. 7  
O pti o nal Ge n o mics I nitiati ve Sa m ple  ................................................................... 4 3 
9  
S T A TI S TI C A L C O N SI D E R A TI O N S  ................................................................... 4 3 
9. 1  
Statistical H y p ot heses  ........................................................................................... 4 3 
9. 2  
Sa m ple Size Deter mi nati o n  .................................................................................. 4 3 
9. 3  
P o p ulati o ns f or A nal yses  ...................................................................................... 4 3 
9. 4  
Statistical A nal yses  ............................................................................................... 4 4 
9. 4. 1  
Ge neral C o nsi derati o ns  ......................................................................................... 4 4 
9. 4. 2  
C O VI D -1 9 C o nsi derati o ns  ................................................................................... 4 5 
9. 4. 3  
Efficac y  ................................................................................................................. 4 5 
9. 4. 3. 1  
Pri mar y E n d p oi nt .................................................................................................. 4 5  
9. 4. 3. 2  
Sec o n dar y E n d p oi nts ............................................................................................ 4 6  
9. 4. 3. 3  
E x pl orat or y E n d p oi nts  .......................................................................................... 4 8 
9. 4. 4  
Safet y  .................................................................................................................... 4 8 
9. 5  
I nteri m A nal yses ................................................................................................... 4 9 
9. 6  
Data M o nit ori n g C o m mittee  ................................................................................. 4 9 
1 0  
S U P P O R TI N G
 D O C U M E N T A TI O N
 A N D
 O P E R A TI O N A L
 
C O N SI D E R A TI O N S  ............................................................................................ 4 9 
1 1  
R E F E R E N C E S  ..................................................................................................... 8 1 
 
LI S T O F FI G U R E S  
Fi g ure 1  
St u d y Desi g n ............................................................................................... 1 1  
 
LI S T O F T A B L E S  
Ta ble  1 
Sc he d ule of Acti vities  ................................................................................. 1 2 
Ta ble 2   
O bjecti ves a n d E n d p oi nts ............................................................................ 1 7 
Ta ble 3   
I n vesti gati o nal Pr o d uct ................................................................................ 2 5 
Ta ble 4  
Restricte d Me dicati o ns  ................................................................................ 2 9 
Ta ble 5  
La b orat or y Safet y Varia bles  ....................................................................... 3 6 
Ta ble 6  
P o p ulati o ns f or A nal ysis  ............................................................................. 4 3 
Ta ble 7   
A nal ysis Peri o ds .......................................................................................... 4 4 
 
LI S T O F A P P E N DI C E S  
A p pe n di x A  
Re g ulat or y, Et hical, a n d St u d y O versi g ht C o nsi derati o ns .......................... 4 9  
A p pe n di x B  
A d verse E ve nts: Defi niti o ns a n d Pr oce d ures f or Rec or di n g, E val uati n g, 
F oll o w- u p, a n d Re p orti n g ........................................................................... 5 5  
A p pe n di x C 
Electr o nic Patie nt -Re p o rte d O utc o mes ....................................................... 6 0 
A p pe n di x D  
Ma na ge me nt of St u d y Pr oce d ures D uri n g t he C O VI D- 1 9 Pa n de mic ........ 7 6  

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y   
7 of 8 2  
A p pe n di x E  
A b bre viati o ns .............................................................................................. 7 8  
A p pe n di x F  
Pr ot oc ol A m e n d me nt Hist or y ..................................................................... 8 0 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 0  of 8 2  
Discl os ure St ate me nt:  
T his is a  parallel -gr o u p, n o n -i n dicati o n-see ki n g inter ve nti o n - m o del n utriti o n st u d y wit h 
2 a r ms t hat is o pe n-la bel. 
N u m ber of P artici p a nts:  
A p pr o xi matel y 3 8 2 partici pa nts will be scree ne d  a n d 1 9 1 e nr olle d t o ac hie ve 1 6 2 ra n d o mise d 
( 8 1 per treat me nt ar m) t o st u d y i nter ve nti o n. Secti o n 9. 2, Sa m ple Size Deter mi nati o n, e x plai ns 
h o w scree ni n g fail ures are defi ne d.  
N ote : ‘E nr olle d ’ mea ns a partici pa nt ’s, or t heir le gall y acce pta ble re prese ntati ve’s, a gree me nt 
t o partici pate i n a clinical st u d y f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt pr ocess. 
P ote ntial partici pa nts w h o are scree ne d f or t he p ur p ose of deter mi ni n g eli gi bilit y f or t he st u d y, 
b ut are n ot ra n d o ml y assi g ne d/assi g ne d i n t he st u d y, are c o nsi dere d ‘scree n failures’, u nless 
ot her wise s pecifie d b y t he pr ot oc ol.  
I nter ve nti o n Gr o u ps  a n d D ur ati o n : 
T he st u d y has a d urati o n of 5 m o nt hs of partici pa nt partici pati o n a n d c o nsists of u p t o 7- da ys 
scree ni n g, u p t o 1- m o nt h H K Treat me nt P hase  (all partici pa nt s ta ke S Z C wit h sta n dar d dietar y 
a d vice), 4- m o nt h Diet C o m paris o n P hase ( partici pa nt s are ra n d o mise d t o So C ar m wit h 
sta n dar d dietar y a d vice or t o S Z C ar m wit h e n ha nce d dietar y a d vice), a n d e n ds wit h a 
f oll o w- u p visit ( 2 wee ks [ 1 4 ± 3 da ys] t o matc h dial ysis sc he d ule).  
D at a M o nit ori n g C o m mittee: N o  
St atistic al Met h o ds  
Sa m ple size deter mi nati o n is base d u p o n t he pri mar y o bjecti ve of t he pri mar y esti ma n d, ie, T o 
ev al u ate t he effect of t he c o m bi n ati o n of S Z C a n d e n h a nce d n utriti o n al a dv ice t o c o ns u me 
fr uit a n d ve get a bles as c o m p are d t o S o C i n re d uci n g S- K+ . Wit h 8 0 % p o wer t o reject t he 
pri mar y h y p ot hesis, 8 1 ra n d o mise d partici pa nt s per treat me nt ar m ( 1 6 2 i n t otal) w o ul d be 
re q uire d wit h a 1-si de d al p ha of 0.0 2 5 , ass u mi n g a c o m m o n sta n dar d de viati o n acr oss 
treat me nt gr o u ps of 0. 4 5 a n d a n o n-i nferi orit y mar gi n of 0. 2. It is e x pecte d t hat 1 5 % of 
partici pa nts w h o e nter t he H K Treat me nt  P hase  will n ot c o nti n ue t o t he Diet C o m paris o n 
P hase , a n d c o nse q ue ntl y it is a ntici pate d t hat a p pr o xi matel y 1 9 1 partici pa nts will e nter t he H K 
Treat me nt P hase  i n or der t o ac hie ve 1 6 2 ra n d o mise d. F urt her, t he scree ni n g fail ure rate is 
esti mate d t o be 5 0 %, mea ni n g 3 8 2 partici pa nt s will be e nr olle d. Partici pa nts will be 
ra n d o mise d i nt o t he 4- m o nt h Diet C o m paris o n P hase u ntil t he re q uire d n u m ber of ra n d o mis e d 
partici pa nt s is reac he d, at w hic h p oi nt t he recr uit me nt will st o p. 
A nal ysis p o p ulati o ns are as f oll o ws : All-partici pa nts a nal ysis set, H K treat me nt safet y a nal ysis 
set, full a nal ysis set ( F A S), a n d safet y a nal ysis set ( S A S).  

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 1  of 8 2  
I nfere nce c o ncer ni n g t he pri mar y a nal ysis will be perf or me d at t he 1-si de d 2. 5 % si g nifica nce 
le vel. All p oi nt esti mates will be prese nte d t o get her wit h c o nfi de nce i nter vals of 2-si de d 9 5 % 
c o vera ge, wit h g ui da nce i ncl u de d i n o ut p uts w here i nfere nce is base d u p o n 1 tail of t he 
i nter val. 
1. 2  
Sc he m a  
Fi g ure 1 
St u d y Desi g n  
  
A b bre viati o ns: H K = h y per kalae mia; K +  = p otassi u m; LI DI = l o n g i nter dial ytic - dial ysis i nter val; N = n u m ber of partici pa nts; 
N K = n or m o kalae mia; S o C = sta n dar d of care; S Z C = s o di u m zirc o ni u m c ycl osilicate.  
N ote: O nl y partici pa nt s wit h S- K +  ≤5. 5 m m ol/ L o n 5 or 1 0 g S Z C at  e n d of H K Treat me nt P hase  will be ra n d o mi se d.  
 
1. 3  
Sc he d ule of Acti vities  
 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 2  of 8 2  
Ta ble  1 
Sc he d ule of Acti vities  
Pr oce d ure  
Scree ni n g/  
E nr oll me nt a 
H K Tre at me nt P h ase b  
Diet C o m p aris o n P h ase  
F oll o w- u p c 
E D d  
Det ails i n C li nic al 
St u d y Pr ot oc ol ( C S P)  
Secti o n or A p pe n di x  
M o nt h 1  
M o nt h 2  
M 3  
M 4  
M 5  
Visit e 
1  
2  
3  
4 f  
5f  
6g  
7  
8  
9  
1 0  
1 1  
1 2  
1 3 
Visit Wi n d o w ( Da ys)  
-7 t o - 1  
0  
± 1  
± 1  
± 1  
± 1  
± 1  
± 1  
± 1  
± 3  
± 3  
± 3  
  
  
 
Electr o nic i nf or me d 
c o nse nt h ( via e-de vice at 
site) 
X  
  
  
  
 
 
  
  
  
 
  
  
  
 
Secti o n  5. 1 
Eli gi bilit y criteria  
X  
  
  
  
  
  
  
  
  
  
  
  
  
  
Secti o ns  5. 1  a n d 5. 2 
De m o gra p h y 
X  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
P h ysical e xa mi nati o n i 
  
X  
  
  
  
X  
  
  
  
  
  
X  
  
X 
Secti o n  8. 2. 1   
Hei g ht 
  
X  
  
  
  
  
  
  
  
  
  
  
  
 
Secti o n  8. 2. 1   
Lea n wei g ht, trice ps s ki n -
f ol d t hic k nessi 
  
X  
  
  
  
X  
  
  
  
  
  
X  
  
X 
Secti o n  8. 2. 1  
Me dical hist or y j 
X  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
Ser u m pre g na nc y test 
( W O C B P o nl y) 
X  
  
  
  
 
 
  
  
  
 
  
  
  
 
Secti o n  8. 3. 7  
Ser u m K +  meas ure me nt i 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X 
Secti o n  8. 1. 1  
Cli nical safet y la b orat or y 
assess me nts i 
X  
  
  
  
  
X  
  
  
  
 
 
X 
 
X 
Secti o n  8. 2. 4  
E C G i 
X  
X  
  
  
  
X  
  
  
  
  
  
X  
X  
X 
Secti o n  8. 2. 3  
Vital si g ns d, i 
  
X  
  
  
  
X  
  
  
  
  
  
X  
X  
X 
Secti o n  8. 2. 2  
I D W Gk 
  
X  
  
  
  
X  
  
  
  
  
  
X  
  
X 
Secti o n  8. 2. 5. 3  
Dr u g dis pe nsati o n/ Dr u g 
acc o u nta bilit y 
 
X  
X  
X  
X  
X l  
Xl  
Xl  
Xl  
Xl  
Xl  
Xm   
 
X m  
Secti o ns  6. 1  a n d 6. 2  
A Es / S A Es 
X  
X  
X  
X  
X 
X 
X  
X  
X  
X  
X 
X 
X  
X  
S ecti o n 8. 3 
Pri or/ C o nc o mita nt 
me dicati o n  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X 
Secti o n  6. 5 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 3  of 8 2  
Pr oce d ure  
Scree ni n g/  
E nr oll me nt a 
H K Tre at me nt P h ase b  
Diet C o m p aris o n P h ase  
F oll o w- u p c 
E D d  
Det ails i n C li nic al 
St u d y Pr ot oc ol ( C S P)  
Secti o n or A p pe n di x  
M o nt h 1  
M o nt h 2  
M 3  
M 4  
M 5  
Visit e 
1  
2  
3  
4 f  
5f  
6g  
7  
8  
9  
1 0  
1 1  
1 2  
1 3 
Dial ysate K +  prescri pti o n  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X 
Secti o n  6. 5. 2  
Dial ysis prescri pti o n n 
X  
  
  
  
  
X  
X  
X  
X  
X  
X  
X  
  
 
Secti o n  8. 2. 5. 1  
Dial ysis a de q uac y o 
X  
  
  
  
  
  
  
  
  
  
  
X  
  
 
Secti o n  8. 2. 5. 2  
P R Os ( K D Q O L -3 6, E Q - 5 D-
5 L, T S Q M -9, P GI C) v ia e-
de vice at sitep 
  
X  
  
  
 
X 
  
  
  
  
  
X  
  
X 
Secti o n  8. 1. 2  
N o o m a p p q 
  
X  
  
  
  
  
  
  
  
  
  
  
  
 
Secti o ns  6. 1. 2, 6. 1. 3  a n d 
6. 1. 4 
Sta n dar d diet a d vice  
  
X  
X  
X  
X  
  
  
  
  
  
  
  
  
Xr 
Secti o n  6. 1. 2  
Sta n dar d diet a d vice ( S o C 
ar m i n Diet C o m paris o n 
P hase ) 
  
  
  
  
  
X  
X  
X  
X  
X  
X  
X  
  
 
Secti o n  6. 1. 2  
E n ha nce d diet a d vice ( S Z C 
ar m i n Diet C o m paris o n 
P hase ) 
  
  
  
  
  
X  
X  
X  
X  
X  
X  
X  
  
 
Secti o n  6. 1. 3  
A b bre viati o ns: A E = a d verse e ve nt; E C G = electr ocar di o gra m; E D = Earl y Disc o nti n uati o n; E Q -5 D -5 L = E ur o Q ol -5 Di me nsi o ns -5 Le vels;  H K = h y per kalae mia; I D W G = 
i nter dial ytic wei g ht gai n; K+  = p ot assi u m; K D Q O L -3 6 = Ki d ne y Disease a n d Q ualit y of Life -3 6 ite m; M = m o nt h; P GI C = Patie nts’ Gl o bal I m pressi o n of C ha n ge; P R O = p atie nt-
re p orte d o utc o me; S A E = seri o us a d verse e ve nt; S o C = sta n dar d of care; S Z C = s o di u m zirc o ni u m c ycl osilicate; T S Q M -9 = A b bre viate d Treat me nt Satisfacti o n Q uesti o n naire f or 
Me dicati o n ( 9 ite ms); W O C B P = w o ma n of c hil d beari n g p ote ntial.  
 
a 
Scree ni n g P hase d urati o n: U p t o 7 da ys bef ore Da y 0.  
b 
H K Treat me nt P hase d urati o n: U p t o 1 m o nt h.  
c F oll o w- u p P hase d urati o n: 1 4 ± 3 da ys after pre vi o us visit . I ncl u des partici pa nts w h o ha ve bee n e nr olle d i nt o t he H K Treat me nt P hase  b ut n ot bee n ra n d o mi se d i nt o t he Diet 
C o m paris o n P hase . 
d 
A p plica ble f or E D pri or t o t he e n d of st u d y treat me nt.  
e 
Visits 1 t o 1 2 re q uire d t o be perf or me d at a l o n g i nter dial ytic-dial ysis i nter val  visit . 
f Visits 4 a n d 5 if nee de d; partici pa nt s wit h c o ntr olle d S- K +  le vels ca n be ra n d o mise d earlier. 
g  Ra n d o mis ati o n occ urs at Visit 6 . O nl y partici pa nt s wit h S- K +  ≤5. 5 m m o l/ L o n 5 or 1 0 g S Z C will be ra n d o mise d. 
h  I C F ca n be o btai ne d u p t o 7 da ys pri or t o st u d y s pecific assess me nts. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 4  of 8 2  
i 
Pr oce d ure t o be perf or me d bef ore dial ysis.  
j C O VI D -1 9 vacci nati o n bef ore e nr ol me nt s h o ul d be ca pt ure d u n der “ me dical hist or y”  a n d u n der “ pri or me dicati o n”.  
k  C urre nt pre -dial ysis wei g ht mi n us pre vi o us p ost -dial ysis wei g ht ( meas ure d at i m me diate dial ysis sessi o n pri or t o t he st u d y visit) i n K g.  
l  Dr u g dis pe nsati o n i n S Z C ar m o nl y.  
m  O nl y dr u g acc o u nta bilit y at Visit 1 2 a n d at E D.  
n 
Bl o o d fl o w ( Q b, m L / mi n), ti me o n dial ysis ( mi n utes). 
o 
s p Kt/ V a n d/ or urea re d ucti o n rati o; rec or d t he m ost rece nt val ue b ut t his s h o ul d be n o ol der t ha n 5 wee ks.  
p 
P R Os are t o be c ollecte d bef ore treat me nt i nitiati o n o n Visits 2 a n d 6 . P GI C t o be c ollecte d at Visit 6 , 12, a n d E D visits o nl y.  
q 
Create t he N o o m acc o u nt a n d trai n t he partici pa nt s o n N o o m a p plicati o n. Partici pa nt s are e x pecte d t o trac k t heir dail y f o o d i nta ke via t he N o o m a p p u ntil Visit 1 2. 
r  I n case of earl y disc o nti n uati o n, all partici pa nt s will be pr o vi de d wit h sta n dar d diet a d vice. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 5  of 1 6  
2  
I N T R O D U C TI O N 
S o di u m zirc o ni u m c ycl osilicate ( S Z C) is a n o vel n o n- a bs or be d zirc o ni u m silicate t hat 
prefere ntiall y ca pt ures p otassi u m  ( K+ ) i n e xc ha n ge f or h y dr o ge n a n d s o di u m t hat is bei n g 
de vel o pe d f or t he treat me nt of h y per kalae mia ( H K) i n a d ult patie nts. S Z C ( bra n d na me 
L O K E L M A ® ) is a p pr o ve d i n t he U nite d States ( U S), E ur o pea n U ni o n, Ca na da, Ja pa n, C hi na, 
a n d Brazil. 
2. 1  
St u d y R ati o n ale  
Prescri bi n g S Z C  wit h e n ha nce d n utriti o nal a d vice t o partici pa nts wit h h y per kalae mia o n 
hae m o dial ysis will re d uce ser u m K +  ( S- K+ ) a n d e na ble t he c o ns u m pti o n of m ore fr uit a n d 
ve geta bles a n d m ore satisf yi n g diet. T he st u d y ai ms t o s h o w t hat partici pa nt s usi ng S Z C  
ac hie ve S- K +  re d ucti o n as well as partici pa nts o n S o C ( ot her t ha n K +  bi n ders), wit h o ut t he 
nee d f or restricti n g K +  i n t he diet. 
2. 2  
B ac k gr o u n d  
T here is gr o wi n g e vi de nce s u p p orti n g t he p ositi ve effects of pla nt- base d dietar y patter ns. 
Dietar y a d vice t hat e nc o ura ges i ncrease d fr uit a n d ve geta ble i nta ke c o ul d be a n effecti ve t o ol 
t o re d uce m or bi dit y a n d m ortalit y i n pe o ple wit h ki d ne y disease ( Wai et al. 2 0 1 7). T his st u d y 
ai ms t o s h o w t hat f or hae m o dial ysis patie nts wit h H K, treat me nt wit h S Z C t o get her wit h 
e n ha nce d n utriti o nal a d vice e nc o ura gi n g t he c o ns u m pti o n of fr uit a n d ve geta bles is as 
effecti ve as S o C, w hic h i ncl u des dietar y restricti o n of K + -c o ntai ni n g f o o ds, i n mai ntai ni n g 
S- K +  i n t he ra n ge 3. 5 – 5. 5 m m ol/ L.
Healt h y diet patter ns ha ve bee n wi del y li n ke d t o better healt h a n d healt h o utc o mes. 
Diets ric h i n ve geta bles a n d fr uits, w hile l o w i n fats, meats , a n d s weete ne d pr o d ucts, ha ve 
bee n i de ntifie d as heal t h y dietar y patter ns a n d ha ve s h o w n pr otecti ve ass ociati o ns wit h 
m or bi dit y a n d m ortalit y. S uc h diets ha ve bee n s h o w n t o l o wer bl o o d press ure i n 
pre h y perte nsi ve a n d h y perte nsi ve a d ults, a n d ha ve bee n ass ociate d wit h l o wer ris ks of 
car di o vasc ular a n d cere br o vasc ular disease i n o bser vati o nal st u dies (Li u et al. 2 0 1 7 ). 
A m o n g ki d ne y o utc o mes e xa mi ne d, a healt hier fr uit a n d ve geta ble ric h diet has bee n 
ass ociate d wit h sl o wer esti mate d gl o mer ular filtrati o n rate decli ne (Ki m et al. 2 0 1 9)  a n d wit h 
l o wer o d ds of i nci de nt c hr o nic ki d ne y disease (C K D ). I n a d diti o n, a n i nter ve nti o nal st u d y 
f o u n d t hat a dietar y patter n, ric h i n fr uits a n d ve geta bles, atte n uate d mar kers of ki d ne y i nj ur y 
a m o n g pers o ns wit h macr oal b u mi n uria (G ora ya et al. 2 0 1 9 ). 
T he mai n s o urce of re nal aci d l oa d c o mes fr o m diet, a n d t he mai n s o urce of dietar y bala nce is 
pr o vi de d b y K + -c o ntai ni n g a mi n o aci ds pri nci pall y f o u n d i n fr uits a n d ve geta bles 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 6  of 1 7  
(Sie ner  2 0 1 8). It has bee n s h o w n t hat fr uits a n d ve geta bles ha ve a si milar effect o n meta b olic 
aci d osis as  s o di u m bicar b o nate ta blets (G ora ya et al. 2 0 1 4 ). 
O ne of t he mai n wa ys of e xcreti n g K +  o nce t he ki d ne y is i m paire d is b y e xcreti o n i n t he st o ol. 
K +  e xcreti o n i n t he st o ol is pr o p orti o nal t o  t he a m o u nt of st o ol pr o d uce d (Ha yes et al. 1 9 6 7 ), 
a n d dial ysis patie nts wit h c o nsti pati o n ha ve si g nifica ntl y h i g her S- K +  t ha n t h ose wit h o ut 
c o nsti pati o n (El - S har ka w y et al. 2 0 0 9). 
A detaile d descri pti o n of t he c he mistr y, p har mac ol o g y, efficac y, a n d safet y of S Z C  is pr o vi de d 
i n t he I n vesti gat or’s Br oc h ure (I B). 
2. 3  
Be nefit/ Ris k Assess me nt  
T he pri mar y be nefit f or partici pa nts ra n d o mi se d t o S Z C treat me nt is e x pecte d t o be t he 
mai nte na nce of n or m o kalae mia d uri n g t he l o n g i nter dial ytic-dial ysis i nter val ( LI DI ), i n li ne 
wit h w hat was o bser ve d  i n t he DI A LI Z E st u d y. F urt her, s h o ul d t he st u d y h y p ot hesis pr o ve 
tr ue, partici pa nt s ta ki n g S Z C will be a ble t o c o ns u me a healt h y diet i ncl u di n g m ore fr uit a n d 
ve geta bles. S uc h dietar y c ha n ges are e x pecte d t o ha ve partici pa nt be nefits i ncl u di n g i m pr o ve d 
q u alit y of life a n d satisfacti o n wit h treat me nt.  
Partici pa nts treate d wit h S o C ma y n ot o btai n a n y be nefit i n ter ms of h y per kala e mia c orrecti o n 
a n d mai nte na nce b ut ma y be nefit fr o m a cl oser f oll o w-u p. Partici pa nts will recei ve alter nati ve 
t hera pies w he ne ver cli nicall y i n dicate d.  
A n esta blis he d d ose a dj ust me nt al g orit h m will be use d d uri n g t he st u d y t o titrate S Z C d oses t o 
e na ble partici pa nts t o ac hie ve a n d mai ntai n pre- dial ysis n or m o kala e mia after t he LI DI. I n 
acc or da nce wit h t he al g orit h m, t he d ose ma y be i n crease d, re d uce d , or ke pt u nc ha n ge d, 
de pe n di n g o n t he c urre nt K +  c o nce ntrati o n, a da pti n g t he d osi n g re gi me n t o eac h partici pa nt 
a n d pre ve nti n g u n necessaril y hi g h e x p os ure t o t he pr o d uct. 
T he ris ks i de ntifie d wit h S Z C treat me nt i ncl u de h y p o kalae mia a n d o e de ma-relate d e ve nts 
(i ncl u des fl ui d o verl oa d, fl ui d rete nti o n, ge neralise d oe de ma, h y per v ol ae mia, l ocali se d 
o e de ma, o e de ma, peri p heral o e de ma, peri p heral s welli n g). I n t his st u d y, t he ris k f or 
h y p o kala e mia is miti gate d b y peri o dic m o nit ori n g of S- K +  a n d a dj ust me nt of t he S Z C d ose as 
necessar y. Oe de ma ca n be ma na ge d b y c o nser vati ve meas ures i n li ne wit h sta n dar d cli nical 
practice. N o a d diti o nal safet y ris ks were i de ntifie d i n t he DI A LI Z E st u d y.  
I n c o ncl usi o n, t he fa v o ura ble be nefit-ris k rati o t hat has bee n esta blis he d f or S Z C i n t he 
cli nical de vel o p me nt pr o gra m re mai ns p ositi ve w he n S Z C is use d t o treat h y per kal ae mia i n 
partici pa nts o n c hr o nic hae m o dial ysis, as s h o w n i n t he DI A LI Z E st u d y. 
M ore detaile d i nf or mati o n a b o ut t he k n o w n a n d e x pecte d be nefits a n d p ote ntial ris ks of S Z C  
ma y be f o u n d i n t he  I B. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 9  of 8 2  
3. 1  
Esti m a n ds f or Pri m ar y O bjecti ve  
I n li ne wit h t he I C H E 9 ( R 1) a d de n d u m, 5 attri b utes (treat me nt, p o p ulati o n, e n d p oi nt, 
i nterc urre nt e ve nts, a n d p o p ulati o n le vel s u m mar y) ha ve bee n s pecifie d t o tra nslate t he 
pri mar y a n d sec o n dar y efficac y o bjecti ves i nt o treat me nt effects t hat are t o be esti mate d 
(esti ma n ds). 
•  T he treat me nt c o n diti o n of i nte rest is: 
o  S Z C  d ose d as per l ocal la bel t o c o ntr ol H K a n d mai ntai n n or m o kalae mia i n 
a d diti o n t o S o C dietar y a d vice f or t he u p t o 1- m o nt h H K Treat me nt P hase  f oll o we d 
b y t he 4- m o nt h Diet C o m paris o n P hase  (S Z C  wit h e n ha nce d n utriti o n a d vice 
vers us S o C, i ncl u di n g sta n dar d dietar y a d vice) f or t he f ull 5 -m o nt h treat me nt 
d urati o n. 
•  T he treat me nt effect is assesse d b y t he pri mar y efficac y e n d p oi nt of c ha n ge fr o m 
baseli ne i n S- K +  le vels o ver t he M 3, M 4, a n d M 5 visits. 
•  T he p o p ulati o n of partici pa nt s tar gete d is a d ults wit h H K  as defi ne d b y t he 
i ncl usi o n/e xcl usi o n criteria w h o are a ble t o c o m plete t he H K Treat me nt P hase . 
•  I nterc urre nt e ve nts are ha n dle d t hr o u g h a c o m bi nati o n of a treat me nt p olic y strate g y a n d 
a c o m p osite strate g y. S pecificall y, t he f oll o wi n g e ve nts w hic h precl u de t he c ollecti o n of 
data f or t he pri mar y esti ma n d as defi ne d i n S ecti o n 9. 4. 3. 1 will be ha n dle d acc or di n g t o 
t he ta ble bel o w: 
I nterc urre nt e ve nt 
D at a c ollecti o n a n d a n al ysis  
Pre mat ure treat me nt 
disc o nti n uati o n d ue t o lac k of 
efficac y or p h ysicia n’s decisi o n  
S u bjects will be f oll o we d a n d data c ollecte d will be a nal yse d after 
t he i nterc urre nt e ve nt i n li ne wit h a treat me nt p olic y strate g y . 
I n t he case of missi n g data after treat me nt disc o nti n uati o n, val ues 
will be i m p ute d t hr o u g h a m ulti ple i m p utati o n ( MI) pr oce d ure.  
Pre mat ure treat me nt 
disc o nti n uati o n d ue t o reas o ns 
ot her t ha n lac k of efficac y or 
p h ysicia n’s decisi o n  
S u bjects will be f oll o we d a n d data c ollecte d after t he i nterc urre nt 
e ve nt i n li ne wit h a treat me nt p olic y strate g y. 
I n t he case of missi n g data after treat me nt disc o nti n uati o n, val ues 
will be i m p ute d t hr o u g h a MI pr oce d ure.  
I ntr o d ucti o n of resc ue t hera p y of a 
K +  bi n der f or H K  
S u bjects will be f oll o we d a n d data c ollecte d after t he i nterc urre nt 
e ve nt f or re p orti n g p ur p os es; h o we ver , t his data will n ot be use d f or 
t he pri mar y a nal ysis of t he pri mar y esti ma n d. 
All val ues after i ntr o d ucti o n of resc ue me dicati o n will be i m p ute d 
usi n g a c o m p osite p ol ic y t hr o u g h a MI pr oce d ure . 
•  T he treat me nt effect will be q ua ntifie d b y via re c o m bi nati o n of t he least s q uares ( L S) 
mea n of t he c ha n ge fr o m baseli ne i n S- K +  le vels acr oss t he M 3, M 4, a n d M 5 visits, 
o btai ne d fr o m a re peate d meas ures a nal ysis of c o varia nce ( A N C O V A ) perf or me d 
m ulti ple ti mes o n MI  data as o utli ne d i n Secti o n  9. 4. 3. 1. 
Details re gar di n g se nsiti vit y esti ma n ds f or t he pri mar y o bjecti ve a n d esti ma n ds f or t he 
sec o n dar y o bjecti ve will be i ncl u de d wit hi n t he S tatistical A nal ysis P la n ( S A P). 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 0  of 8 2  
4  
S T U D Y D E SI G N  
4. 1  
O ver all  Desi g n  
T his is a P hase I V, ra n d o mi se d, c o ntr olle d, o pe n -la bel, parallel-gr o u p, m ultice nt re, 
pr os pecti ve st u d y t o e val uate t he effect of t he c o m bi nati o n of S Z C  a n d e n ha nce d n utriti o nal 
a d vice t o c o ns u me fr uit a n d ve geta bles as c o m pare d t o S o C i n re d uci n g S- K+  le vels i n 
partici pa nts wit h h y per kalae mia o n hae m o dial ysis . 
4. 1. 1  
St u d y C o n d uct Miti g ati o n D ur i n g St u d y Disr u pti o ns D ue t o 
C ases of Ci vil Crisis, N at ur al Dis aster, or P u blic He alt h Crisis  
T he g ui da nce gi ve n bel o w s u perse des i nstr ucti o ns pr o vi de d else w here i n t his Cli nical St u d y 
Pr ot oc ol ( C S P ) a n d s h o ul d be i m ple me nte d o nl y d uri n g cases of ci vil crisis, nat ural disaster, 
or p u blic healt h crisis ( e g, d uri n g q uara nti nes a n d res ulti n g site cl os ures, re gi o nal tra vel 
restricti o ns, a n d c o nsi derati o ns if site pers o n nel or st u d y partici pa nts bec o me i nfecte d wit h 
C O VI D - 1 9 or si milar pa n de mic i nfecti o n) t hat w o ul d pre ve nt t he c o n d uct of st u d y- relate d 
acti vities at st u d y sites, t here b y c o m pr o misi n g t he st u d y site staff or t he partici pa nt’s a bilit y t o 
c o n d uct t he st u d y. T he i n vesti gat or or desi g nee s h o ul d c o ntact t he st u d y s p o ns or t o disc uss 
w het her t he miti gati o n pla ns bel o w s h o ul d be i m ple me nte d. 
To e ns ure c o nti n uit y of t he cli nical st u d y d uri n g a ci vil crisis, nat ural disaster, or p u blic healt h 
crisis, c ha n ges ma y be i m ple me nte d t o e ns ure t he safet y of st u d y partici pa nts, m ai ntai n 
c o m plia nce wit h G o o d Cli nical Practice ( G C P), a n d mi ni mi se ris ks t o st u d y i nte grit y.  
W here all o wa ble b y l ocal healt h a ut h orities, et hics c o m mittees, healt hcare pr o vi der ( H C P) 
g ui deli nes ( e g, h os pital p olicies) , or l ocal g o ver n me nt, t hese c ha n ges ma y i ncl u de t he 
f oll o wi n g o pti o ns: 
•  
O btai ni n g c o nse nt f or t he miti gati o n pr oce d ures a n d d oc u me nti n g t his i n t he s o urce data 
•  
Tele me dici ne visit: Re m ote c o ntact wit h t he partici pa nts usi n g telec o m m u nicati o ns 
tec h n ol o g y i ncl u di n g p h o ne calls, virt ual or vi de o visits, a n d m o bile healt h de vices. 
F or f urt her details o n st u d y c o n d uct d uri n g ci vil crisis, na t ural disaster, or p u blic healt h crisis, 
refer t o A p pe n di x D.  
4. 1. 2  
U p t o 1 -m o nt h H K Tre at me nt P h ase ( all p artici p a nt s) 
Partici pa nt s will f oll o w la belle d i nstr ucti o ns f or d osi n g dial ysis partici pa nt s, starti n g at 5 g o n 
n o n- dial ysis da ys. At wee kl y i nter vals partici pa nt s ca n be titrate d u p or d o w n i n 5-g ste ps t o a 
ma xi m u m of 1 5 g o n n o n- dial ysis da ys a n d a mi n i m u m of 5 g o n n o n- dial ysis da ys, t o kee p 
S- K +  i n t he ra n ge of 3. 5- 5. 5 m m ol/ L. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 1  of 8 2  
K +  will be c orrecte d wit h S Z C  as per l ocal la bel. Partici pa nts will recei ve dietar y a d vice 
c o nsiste nt wit h S o C at t hat site , i ncl u di n g K+  restricti o n. Dietar y a d vice will be gi ve n b y 
dietitia ns at st u d y visits.  
4. 1. 3  
4- m o nt h Diet C o m p aris o n P h ase ( 2 ar ms)  
Ra n d o misati o n will occ ur at Visit 6 . O nl y partici pa nt s wit h S- K +  ≤5. 5 m m ol/ L o n 5 or 1 0 g 
S Z C will be ra n d o mis e d. Partici pa nt s o n 1 5 g S Z C will be c o nsi dere d as ra n d o misati o n 
fail ures. 
S Z C ar m:  Partici pa nt s will c o nti n ue ta ki n g S Z C, w hic h ca n be titrate d u p or d o w n as 
descri be d i n Secti o n  4. 1. 2 t o mai ntai n S- K +  i n t he ra n ge 3. 5- 5. 5 m m ol/ L; partici pa nt s will als o 
recei ve e n ha nce d n utriti o nal a d vice t o c o ns u me fr uit a n d ve geta bles. A d vice will be pr o vi de d 
b y dietitia ns at st u d y visits a n d b y N o o m a p p bet wee n visits. 
S o C ar m: S Z C will be wit h dra w n a n d partici pa nt s will recei ve S o C as per site practice, 
i ncl u di n g dietar y K+  restricti o n. Dietar y a d vice will be gi ve n b y dietitia ns at st u d y visits a n d 
b y N o o m a p p bet wee n st u d y visits. 
4. 1. 4  
F oll o w - up P h ase ( all p artici p a nt s) 
U p o n c o m pleti o n of t he st u d y, or earl y disc o nti n uati o n, all partici pa nts t hat ha ve recei ve d 
st u d y dr u g, i ncl u di n g t h ose w h o ha ve bee n e nr olle d i nt o t he H K Treat me nt P hase  b ut n ot bee n 
ra n d o mise d i nt o t he Diet C o m paris o n P hase , will pr ocee d t o t he p ost-treat me nt f oll o w- u p visit 
after 1 4± 3 da ys. After c o m pleti n g t he st u d y, or earl y disc o nti n uati o n, partici pa nt s will recei ve 
S o C a n d sta n dar d diet a d vice as deter mi ne d b y t heir treati n g p h ysicia n. 
4. 2  
Scie ntific R ati o n ale f or St u d y Desi g n  
F or t he p ur p oses of t his st u d y, t he acce pte d ra n ge f or n or m o kalae mia of 3. 5 – 5. 5 m m ol/ L has 
bee n selecte d f oll o wi n g a d vice fr o m t he steeri n g c o m mittee t o ali g n wit h ne p hr ol o gist 
perce pti o ns of H K i n dial ysis patie nts a n d t o cl osel y reflect t he ra n ge c o m m o nl y re gar de d as 
acce pta ble i n t hese patie nts.  
4. 3  
J ustific ati o n f or D ose 
F or patie nts o n dial ysis, S Z C s h o ul d o nl y be d ose d o n n o n- dial ysis da ys. T he rec o m me n de d 
starti n g d ose is 5 g o nce dail y. To esta blis h n or m o kalae mia (i n t he ra n ge c o m m o nl y re gar de d 
as acce pta ble i n t hese patie nts [ 3. 5 -5. 5 m m ol/ L]) , t he d ose ma y be titrate d u p or d o w n wee kl y 
base d o n t he pre- dial ysis S- K +  val ue after t he LI DI . T he d ose ca n be a dj uste d at i nter vals of 
1 wee k i n i ncre me nts of 5 g u p t o 1 5 g o nce dail y o n n o n- dial ysis da ys. It is rec o m me n de d t o 
m o nit or S- K +  wee kl y w hile t he d ose is a dj uste d; o nce n or m o kalae mia is esta blis he d, S- K +  
s h o ul d be m o nit ore d re g ularl y (e g, m o nt hl y, or m ore fre q ue ntl y base d o n cli nical j u d ge me nt 
i ncl u di n g c ha n ges i n dietar y K+  or me dicati o n affecti n g S- K+ ). 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 2  of 8 2  
4. 4  
E n d of St u d y  Defi niti o n  
A partici pa nt is c o nsi dere d t o ha ve c o m plete d t he st u d y if he/s he has c o m plete d all p hases of 
t he st u d y i ncl u di n g f oll o w- u p visit. 
T he e n d of t he st u d y is defi ne d as t he date of t he last visit of t he last partici pa nt i n t he st u d y.  
E n d of treat me nt is defi ne d as t he date of t he last visit i n t he Diet C o m paris o n P hase 
( Visit 1 2). 
5  
S T U D Y P O P U L A TI O N  
Pr os pecti ve a p pr o val of pr ot oc ol de viati o ns t o recr uit me nt a n d e nr ol me nt 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  
I ncl usi o n Criteri a 
Partici pa nts are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if all of t he f oll o wi n g criteri a a p pl y: 
A ge  
1  
Partici pa nt m ust be ≥1 8 years of a ge at t he ti me of si g ni n g t he i nf or me d c o nse nt. 
T y pe of P artici p a nt a n d Dise ase C h ar acteristics  
2  
Partici pa nts wit h pre vale nt H K ( S- K +  > 5. 5 m m ol/ L at t he e n d of LI DI) n ot re q uiri n g ac ute 
treat me nt. 
3  
Recei vi n g ha e m o dial ysis 3 ti mes a wee k wit h sta ble vasc ular access f or at least 3 m o nt hs 
bef ore scree ni n g visit.  
4  
Partici pa nts w h o ha ve a n d are a ble a n d willi n g t o use s mart p h o ne (a n dr oi d or i O S) 
n utriti o n a p p. 
Se x  
5  
C o ntrace pti ve use b y me n or w o me n s h o ul d be 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 st u dies. 
•  
F e male partici pa nts  of c hil d beari n g p ote ntial m ust ha ve a ne gati ve pre g na nc y 
test (see Secti o n 8. 3. 7 ). 
•  
Fe male partici pa nts m ust be 1 year p ost - me n o pa usal, s ur gicall y sterile, or usi n g 
1 hi g hl y effecti ve f or m of birt h c o ntr ol ( de fi ne d as o ne t hat ca n ac hie ve a fail ure 
rate of less t ha n 1 % per year w he n use d c o nsiste ntl y a n d c orrectl y). T he y s h o ul d 
ha ve bee n sta ble o n t heir c h ose n met h o d of birt h c o ntr ol f or a mi ni m u m of 
3 m o nt hs bef ore e nteri n g t he st u d y a n d willi n g t o re mai n o n t he birt h c o ntr ol 
u ntil 1 2 wee ks after t he last d ose . 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 3  of 8 2  
F or w o me n of c hil d beari n g p ote ntial ( W O C B P; ie, t h ose w h o are n ot c he micall y 
or s ur gicall y sterilise d or w h o are n ot p ost- me n o pa usal) i ncl u de d i n U nite d-
Ki n g d o m sites, hi g hl y effecti ve f or ms of birt h c o n tr ol are defi ne d as f oll o ws: 
a) C o m bi ne d (estr o ge 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  
b)  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: ora l, i njecta ble, i m pla nta ble 
c) I ntra uteri ne de vice (I U D) 
d)  I ntra uteri ne h or m o ne-releasi n g s yste m (I U S) 
e) Bilateral t u bal occl usi o n  
f) 
Vasect o mise d part ner ( vasect o mise d part ner is a hi g hl y effecti ve birt h 
c o ntr ol met h o d pr o vi de d t hat part ner is t he s ole se x ual part ner of t he 
W O C B P partici pa nt a n d t hat t he vasect o mise d part ner has recei ve d me dical 
assess me nt of t he s ur gical s uccess  
g)  Se x ual a bsti ne nce: it is c o nsi dere d a hi g hl y effecti ve met h o d o nl y if defi ne d 
as refrai ni n g fr o m heter ose x ual i nterc o urse d uri n g t he e ntire peri o d of ris k 
ass ociate d wit h t he st u d y treat me nts. T he relia bilit y of se x ual a bsti ne nce 
nee ds t o be e val uate d i n relati o n t o t he d urati o n of t he st u d y a n d t he 
preferre d a n d us ual lifest yle of t he partici pa nt.  
 
I nf or me d C o nse nt  
6  
Ca pa ble of gi vi n g si g ne d i nf or me d c o nse nt as descri be d i n  A p pe n di x A, w hic h i ncl u des 
c o m plia nce wit h t he re q uire me nts a n d restricti o ns liste d i n t he I nf or me d C o nse nt For m 
(I C F) a n d i n t his pr ot oc ol. 
5. 2  
E xcl usi o n Criteri a  
Partici pa nts are e xcl u de d fr o m t he st u d y if a n y of t he f oll o wi n g criteria a p pl y:  
Me dic al C o n diti o ns  
1  
As j u d ge d b y t he i n vesti gat or or s p o ns or , a n y me dical c o n diti o n (i ncl u di n g acti ve, 
cli nicall y si g nifica nt i nfecti o n) t hat ma y p ose a safet y ris k t o t he partici pa nt i n t his st u d y, 
ma y c o nf o u n d safet y or efficac y assess me nts a n d je o par di se t he q ualit y of data, or ma y 
i nterfere wit h st u d y partici pati o n. 
2  
M y ocar dial i nfarcti o n, ac ute c or o nar y s y n dr o me ( S T -ele vati o n m y ocar dial i nfarcti o n , 
n o n- S T -ele vati o n m y ocar dial i nfarcti o n , or u nsta ble a n gi na), str o ke, seiz ure, 
t hr o m b otic/t hr o m b oe m b olic e ve nt (e g, dee p vei n t hr o m b osis or p ul m o nar y e m b olis m, b ut 
e xcl u di n g vasc ular access t hr o m b osis), perc uta ne o us tra nsl u mi nal c or o nar y a n gi o plast y, 
or c or o nar y arter y b y pass graft wit hi n 1 2 wee ks pri or t o scree ni n g visit. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 4  of 8 2  
3  
Se vere le uc oc yt osis ( > 2 0 × 1 0 9/ L) or t hr o m b oc yt osis ( ≥4 5 0 × 1 09/ L) d uri n g scree ni n g. 
4  
P ol yc yt hae mia ( hae m o gl o bi n > 1 4 g/ d L) d uri n g scree ni n g. 
5  
Se vere c o nsti pati o n, b o wel o bstr ucti o n, p ost- o perati ve m otilit y dis or ders.  
6  
Sc he d ule d date f or li vi n g d o n or ki d ne y tra ns pla nt. 
7  
Partici pa nts wit h a life e x pecta nc y of less t ha n 6 m o nt hs.  
8  
Fe males of c hil d beari n g p ote ntial, u nless usi n g c o ntrace pti o n as detaile d i n t he pr ot oc ol 
or se x ual l y a bsti ne nt. 
9  
C urre ntl y pre g na nt (c o nfir me d wit h p ositi ve pre g na nc y test) or breast-fee di n g. 
1 0  Prese nce of car diac arr h yt h mias or c o n d ucti o n defects t hat re q uire i m me diate tre at me nt at 
H C P discreti o n . 
1 1  Hist or y of alc o h ol or dr u g a b use wit hi n 2 years pri or t o scree ni n g visit. 
1 2  Hist or y of Q T pr ol o n gati o n ass ociate d wit h ot her me dicati o ns t hat re q uire d 
disc o nti n uati o n of t hat me dicati o n. 
1 3  C o n ge nital l o n g Q T s y n dr o me or Q T i nter val c orrecte d f or heart rate ( Q Tc) usi n g 
Fri dericia’s met h o d ( Q Tc F) > 5 5 0 ms. 
1 4  S y m pt o matic or u nc o ntr olle d atrial fi brillati o n des pite treat me nt, or as y m pt o matic 
s ustai ne d ve ntric ular tac h ycar dia. S u bjects wit h atrial fi brillati o n c o ntr olle d b y 
me dicati o n are per mitte d.  
1 5  If t he partici pa nt  has e vi de nce of C or o na vir us disease 2 0 1 9 ( C O VI D - 1 9) wit hi n 2 wee ks 
pri or t o scree ni n g (see  A p pe n di x D), t he partici pa nt ca n n ot be e nr olle d i n t he st u d y. 
 
Pri or/ C o nc o mit a nt T her a p y  
1 6  Partici pa nt s treate d wit h S Z C , s o di u m p ol yst yre ne s ulf o nate (S P S: Ka ye xalate ™; 
Res o ni u m ™ A), calci u m p ol yst yre ne s ulf o nate ( C P S: Calci u m Res o ni u m ™), or 
patir o mer ( Veltassa ™)
1 wit hi n 4 wee ks bef ore scree ni n g. 
1 7  Partici pa nts wit h a k n o w n h y perse nsiti vit y or pre vi o us a na p h yla xis t o S Z C or a n y of t he 
e xci pie nts of t he pr o d uct. 
1 8  Partici pa nt s u na ble t o ta ke oral S Z C . 
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce  
1 9  Partici pati o n i n a n ot her cli nical st u d y wit h a n in vesti gati o nal pr o d uct a d mi nistere d d uri n g 
t he m o nt h bef ore scree ni n g2.  
 
1  As a p pr o ve d a n d a vaila ble l ocall y  
2 Partici pa nts vacci nate d wit h C O VI D -1 9 vacci ne w hilst still u n der E mer ge nc y Use Utilisati o n will n ot be 
e xcl u de d fr o m t he st u d y  

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 5  of 8 2  
2 0  I n v ol ve me nt i n t he pla n ni n g a n d/ or c o n d uct of t he st u d y (a p plies t o b ot h Astra Ze neca 
staff a n d/ or staff at t he st u d y site). 
2 1  J u d g me nt b y t he i n vesti gat or t hat t he partici pa nt s h o ul d n ot partici pate i n t he st u d y if t he 
partici pa nt is u nli kel y t o c o m pl y wit h st u d y pr oce d ures, restricti o ns, a n d re q uire me nts. 
2 2  Pre vi o us e nr ol me nt i n t he prese nt st u d y. 
5. 3  
Lifest yle C o nsi der ati o ns  
T here are n o pr oject -s pecific safet y re q uire me nts or restricti o ns f or S Z C . 
5. 4  
Scree n F ail ures  
Scree n fail ures are defi ne d as partici pa nts w h o c o nse nt t o partici pate i n t he cli nical st u d y b ut 
are n ot s u bse q ue ntl y assi g ne d t o st u d y i nter ve nti o n . A mi ni mal set of scree n-fail ure 
i nf or mati 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 partici pa nts t o meet 
t he C o ns oli date d Sta n dar ds of Re p orti n g Trials ( C O N S O R T) p u blis hi n g re q uire me nts a n d t o 
res p o n d t o q ueries fr o m re g ulat or y a ut h orities. Mi ni mal i nf or mati o n i ncl u des de m o gra p h y, 
scree n-fail ure details, eli gi bilit y criteria, a n d a n y serio us a d verse e ve nt s ( S A Es). 
I n di vi d uals w h o d o n ot meet t he criteria f or partici pati o n i n t his st u d y (scree n fail ure) ma y  be 
rescree ne d. O nl y 1 rescree ni n g is all o we d i n t he st u d y. Rescree ne d partici pa nts s h o ul d be 
assi g ne d t he sa me partici pa nt n u m ber as f or t he i nitial scree ni n g. 
At Visit 6, o nl y partici pa nt s wit h S- K +  ≤5. 5 m m ol/ L o n 5 or 1 0 g S Z C will be ra n d o mise d. 
Partici pa nt s o n 1 5 g S Z C are ra n d o misati o n fail ures.  
6  
S T U D Y I N T E R V E N TI O N  
St u d y i nter ve nti o n is defi ne d as a ny i n vesti gati o nal i nter ve nti o n(s), mar kete d pr o d uct(s), or 
place b o i nte n de d t o be a d mi nistere d t o or me dical de vice(s) utilise d b y a st u d y partici pa nt 
acc or di n g t o t he C S P . 
6. 1  
St u d y I nter ve nti o n(s) A d mi nistere d  
6. 1. 1  
I n vesti g ati o n al Pr o d ucts 
Ta ble 3 
I n vesti g ati o n al Pr o d uct 
I nter ve nti o n N a me 
S Z C  
D ose F or m ul ati o n/ U nit D ose 
Stre n gt h  
W hite t o gre y cr ystalli ne p o w der f or oral s us pe nsi o n i n 5 - a n d 1 0-g sac hets  
D os a ge Le vel(s)  
Partici pa nt s i n t he acti ve ar m will recei ve S Z C d ose d as per t he l ocal la bel t o 
c o ntr ol H K a n d mai ntai n n or m o kalae mia . A n y decisi o n t o disc o nti n ue S Z C 
will be u p t o t he treati n g p h ysicia n’s j u d ge me nt a n d as a d vise d b y t he la bel. 
Per t he la bel, S Z C s h o ul d o nl y be d ose d o n n o n -dial ysis da ys. T he 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 6  of 8 2  
rec o m me n de d starti n g d ose is 5 g o nce dail y. T o esta blis h n or m o kalae mia (i n 
t he ra n ge c o m m o nl y re gar de d as acce pta ble i n t hese patie nts [ 3. 5-
5. 5  m m ol/ L]) , t he d ose ma y be titrate d u p or d o w n wee kl y base d o n t he 
pre -dial ysis S- K +  val ue after LI DI . T he d ose ca n be a dj uste d at i nter vals of 
1 wee k i n i ncre me nts of 5 g u p t o 1 5 g o nce dail y o n n o n -dial ysis da ys.  
R o ute of A d mi nistr ati o n  
O ral 
Use 
I n vesti gati o nal pr o d uct 
I M P a n d NI M P 
S o di u m zirc o ni u m c ycl osilicate   
S o urci n g  
Pr o vi de d ce ntrall y b y t he s p o ns or  
P ac k a gi n g a n d L a belli n g  
St u d y i nter ve nti o n will be pr o vi de d i n sac hets pac ke d i n a b o x. Eac h sac het 
a n d b o x will be la belle d i n acc or da nce wit h G M P A n ne x 1 3 a n d per c o u ntr y 
re g ulat or y re q uire me nt. 
A b bre viati o ns: G M P = G o o d Ma n ufact uri n g Practice; H K = h y per kalae mia; I M P = i n vesti gati o nal me dici nal 
pr o d uct; LI DI = l o n g i nter dial ytic -dial ysis i nter val; NI M P = n o n -I M P; S Z C = s o di u m zirc o ni u m c ycl osilicate. 
6. 1. 2  
S o C Diet ar y A d vice  
All partici pa nt s d uri n g t he H K Treat me nt P hase , a n d partici pa nts ra n d o mise d t o t he So C ar m 
of t he Diet C o m paris o n P hase  will recei ve sta n dar d dietar y a d vice i ncl u di n g K +  restricti o n. 
T his a d vice will be pr o vi de d b y dietitia ns at st u d y visits a n d will be c o nsiste nt wit h S o C at 
t hat site a n d will use a m o bile a p p ( N o o m, descri be d bel o w) t o trac k f o o d i nta ke o nl y. 
Partici pa nts will be e nc o ura ge d t o c o ns u me less t ha n 5 0 m m ol K +  per da y. 
6. 1. 3  
E n h a nce d D iet ar y A d vice  
U p o n ra n d o mis ati o n t o t he S Z C  ar m of t he Diet C o m paris o n P hase , partici pa nts will recei ve 
e n ha nce d dietar y a d vice i n a d diti o n t o ta ki n g S Z C . T his will i ncl u de a d vice fr o m dietit ia ns at 
st u d y visits t o c o ns u me fr uit a n d ve geta bles. Partici pa nt s will recei ve dietar y s u p p ort fr o m t he 
N o o m a p p bet wee n visits.  Partici pa nt s will be e nc o ura ge d t o c o ns u me u p t o 7 0 m m ol K +  per 
da y.  
6. 1. 4  
Diet M o bile A p p ( N o o m)  
I n or der t o trac k dietar y c ha n ges, partici pa nts i n b ot h ar ms will be s u p p orte d b y a m o bile a p p 
( N o o m) bet wee n st u d y visits. Partici pa nts will be re q uire d t o e nter i nf or mati o n dail y o n t heir 
f o o d i nta ke. T his a p p will (a) trac k f o o d i nta ke, i ncl u di n g K+ , fr uit a n d ve geta bles, a n d fi bre, 
( b) pr o vi de fee d bac k re gar di n g a n esti mate of dail y K+  c o ns u m pti o n, a n d (c) pr o vi de li ve 
g ui da nce o n f o o d c o ns u m pti o n b y h u ma n c oac hes. 
N o o m is a c o m merciall y a vaila ble m o bile a p p (a n dr oi d a n d i O S) t hat has bee n i n use f or o ver 
7 years a n d c urre ntl y has m ore t ha n 5 0 milli o n users w orl d wi de. T he a p p all o ws partici pa nt s 
t o e nter a n d trac k t heir f o o d i nta ke a n d has a 3. 7 milli o n -ite m pre dicti ve f o o d data base 
bac ke n d, w hic h i ncl u des f o o d ite m K +  c o nte nt. T here are 1 5 p u blis he d st u dies (i ncl u di n g 

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Nat ure a n d B MJ) descri bi n g use of t he a p p, a n d N o o m has recei ve d 4 Nati o nal I nstit utes of 
Healt h ( NI H ) gra nts. 
6. 2  
Pre p ar ati o n/ H a n dli n g/ St or a ge/ Acc o u nt a bilit y  
1)  T he i n vesti gat or or desi g nee m ust c o nfir m a p pr o priate te m perat ure c o n diti o ns ha ve bee n 
mai ntai ne d d uri n g tra nsit f or all st u d y i nter ve nti o n recei ve d a n d a n y discre pa ncies are 
re p orte d a n d res ol ve d bef ore use of t he st u d y i nter ve nti o n. 
2)  O nl y partici pa nts e nr olle d i n t he st u d y ma y recei ve st u d y i nter ve nti o n a n d o nl y a ut h or ised 
staff ma y s u p pl y or a d mi nister st u d y i nter ve nti o n. All st u d y i nter ve nti o n m ust be st ore d i n 
a sec ure, e n vir o n me ntall y c o ntr olle d, a n d m o nit ore d ( ma n ual or a ut o mate d) area i n 
acc or da nce wit h t he la belle d st ora ge c o n diti o ns wit h access li mite d t o t he i n vesti gat or a n d 
a ut h orise d site staff. 
3)  T he i n vesti gat or, i nstit uti o n, or t he hea d of t he me dical i nstit uti o n ( w here a p plica ble) is 
res p o nsi ble f or st u d y i nter ve nti o n acc o u nta bilit y, rec o nciliati o n, a n d rec or d mai nte na nce 
(ie, recei pt, rec o nciliati o n, a n d fi nal dis p ositi o n rec or ds). 
4)  F urt her g ui da nce a n d i nf or mati o n f or t he fi nal dis p ositi o n of u n use d st u d y i nter ve nti o ns 
are pr o vi de d i n t he St u d y Refere nce Ma n ual . 
6. 3  
Me as ures t o Mi ni m ise Bi as: R a n d o mi sati o n a n d Bli n di n g  
T his is a n o pe n -la bel st u d y; h o we ver, t he s pecific i nter ve nti o n t o be ta ke n b y a partici pa nt will 
be ra n d o ml y assi g ne d usi n g a n I nteracti ve Res p o nse Tec h n ol o g y/ Ra n d o misati o n a n d Trial 
S u p pl y Ma na ge me nt (I R T/ R T S M). Bef ore t he st u d y is i nitiate d, t he tele p h o ne n u m ber a n d 
call-i n directi o ns f or t he I R T a n d/ or t he l o g-i n i nf or mati o n a n d directi o ns f or t he R T S M will 
be pr o vi de d t o eac h site. T he site will c o ntact t he I R T/ R T S M pri or t o t he start of  st u d y 
i nter ve nti o n a d mi nistrati o n f or eac h partici pa nt. T he site will rec or d t he i nter ve nti o n 
assi g n me nt o n t he a p plica ble electr o nic C ase Re p ort F or m ( e C R F), if re q uire d. P ote ntial bias 
will be re d uce d b y ce ntral ra n d o misati o n. 
6. 4  
St u d y I nter ve nti o n C o m pli a nce 
W he n partici pa nts are d ose d at t he site, w hic h will occ ur o n n o n- dial ysis da ys a n d s h o ul d be 
ke pt t o a mi ni m u m, t he y will recei ve st u d y i nter ve nti o n directl y fr o m t he i n vesti gat or or 
desi g nee, u n der me dical s u per visi o n. T he date, a n d ti me if a p plica ble, of d ose a d mi nistere d i n 
t he cli nic will be rec or de d i n t he s o urce d oc u me nts a n d rec or de d i n t he e C R F. T he d ose of 
st u d y i nter ve nti o n a n d st u d y partici pa nt i de ntificati o n will be c o nfir me d at t he ti me of d osi n g 
b y a me m ber of t he st u d y  site staff ot her t ha n t he pers o n a d mi nisteri n g t he st u d y i nter ve nti o n. 
W he n partici pa nts self -a d mi nister st u d y i nter ve nti o n(s) at h o me, c o m plia nce wit h st u d y 
i nter ve nti o n will be assesse d at eac h visit. C o m plia nce will be assesse d b y c o u nti n g ret ur ne d 
sachets d uri n g t he site visits a n d d oc u me nte d i n t he s o urce d oc u me nts a n d e C R F. De viati o n(s) 
fr o m t he prescri be d d osa ge re gi me n s h o ul d be rec or de d i n t he e C R F. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 8  of 8 2  
A rec or d of t he n u m ber of S Z C  sac hets dis pe nse d t o a n d ta ke n b y eac h partici pa nt m ust be 
mai ntai ne d  a n d rec o ncile d wit h st u d y i nter ve nti o n a n d c o m plia nce rec or ds. I nter ve nti o n start 
a n d st o p dates, i ncl u di n g dates f or i nter ve nti o n dela ys a n d/ or d ose re d ucti o ns will als o be 
rec or de d i n t he eC R F.  
6. 5  
C o nc o mit a nt T her a p y  
S Z C  ca n tra nsie ntl y i ncrease gastric p H  b y a bs or bi n g h y dr o ge n i o ns t hat ca n lea d t o c ha n ges 
i n s ol u bilit y a n d a bs or pti o n ki netics f or c o-a d mi nistrate d dr u gs wit h p H - de pe n de nt 
bi oa vaila bilit y. T heref ore, S Z C  s h o ul d be a d mi nistere d at least 2 h o urs bef ore or 2 h o urs after 
oral me dicati o ns wit h ga stric p H-de pe n de nt bi oa vaila bilit y.  
E xa m ples of dr u gs t hat s h o ul d be ta ke n 2 h o urs bef ore or after S Z C  t o a v oi d p ossi ble raise d 
gastric p H dr u g i nteracti o n are liste d bel o w: 
Cl ass of Dr u g  
Dr u gs  
Az ole a ntif u n gals  
Ket oc o naz ole, itrac o naz ole, p osac o naz ole  
A nti -HI V dr u gs  
Ataza na vir, nelfi na vir , i n di na vir, rit o na vir, sa q ui na vir, ralte gra vir, 
le di pas vir, ril pi viri ne 
T yr osi ne ki nase i n hi bit ors  
Erl oti ni b, dasati ni b , nil oti ni b  
S Z C  ca n be c o -a d mi nistere d wit h oral me dicati o ns t hat d o n ot e x hi bit p H - de pe n de nt 
bi oa vaila bilit y wit h o ut s paci n g of d osi n g ti mes. 
A n y me dicati o n or vacci ne (i ncl u di n g o ver- t he-c o u nter or prescri pti o n me dici nes, vita mi ns, 
a n d/ or her bal s u p ple me nts, or ot her s pecific cate g ories of i nterest) t hat t he partici pa nt 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 st u d y m ust be rec or de 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 mati o n i ncl u di n g d ose a n d fre q ue nc y. 
H o we ver, if t he partici pa nt recei ve d o ne ( or m ore) C O VI D - 1 9 vacci nati o n(s) pri or t o 
e nr ol me nt t he n t his nee ds t o be rec or de d i n t he e C R F. 
T he i n vesti gat or s h o ul d be c o ntacte d if t here are a n y q uesti o ns re gar di n g c o nc o mita nt or pri or 
t hera p y. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
2 9  of 8 2  
Ta ble 4 
Restricte d Me dic ati o ns  
T y pe of Me dic ati o n/ Tre at me nt  
Ti meli ne/I nstr ucti o ns  
K +  bi n ders i ncl u di n g S P S, C P S, p atir o mer 
O nl y per mitte d t o be use d as resc ue t hera p y t o treat se vere 
H K ( S- K +  > 6. 0 m m ol/ L) after I M P has bee n disc o nti n ue d  
K +  s u p ple me nts or ot her dr u gs a d mi nistere d t o 
raise S- K +  (e g, p otassi u m c hl ori de)  
E xce pt if use d t o treat h y p o kalae mia ( S -K +  < 3. 5  m m ol/ L) 
acc or di n g t o me dical j u d ge me nt  
A b bre viati o ns: C P S = G o o d Ma n ufact uri n g Practice; H K = h y per kalae mia; I M P = i n vesti gati o nal me dici nal 
pr o d uct; S- K +  = ser u m p otassi u m; S P S = s o di u m p ol yst yre ne s ulf o nate.  
6. 5. 1  Resc ue Me dici ne  
F or b ot h ar ms, resc ue t hera p y is defi ne d as a n y t hera pe utic i nter ve nti o n c o nsi dere d necessar y 
i n acc or da nce wit h  l ocal practice patter ns t o re d uce S- K +  i n t he setti n g of se vere H K as 
defi ne d b y p h ysicia n a n d site. 
Treat me nts c o nsi dere d resc ue ma y i ncl u de : 
•  I ntra ve n o us i ns uli n/ gl uc ose or de xtr ose, beta a dre ner gic a g o nists, i ntra ve n o us s o di u m 
bicar b o nate, a n d a n y a d diti o nal dial ysis or ot her f or ms of re nal -re place me nt treat me nts 
w he n use d s pecificall y f or t he treat me nt of se vere H K as defi ne d l ocall y at site. 
•  I n a d diti o n, re d ucti o n i n t he dial ysate K+  c o nce ntrati o n t hat is prescri be d f or t he 
treat me nt of se vere H K d uri n g t he st u d y is als o c o nsi dere d resc ue t hera p y. 
I n vesti gat ors ma y c ha n ge dial ysate bat h as nee de d. 
•  Use of ot her K +  bi n ders i ncl u di n g S P S, C P S, a n d patir o mer. 
Resc ue t hera p y s h o ul d be f oll o we d b y t he a p pr o priate S Z C  d ose a dj ust me nt if a p pr o priate a n d 
pr o per d oc u me ntati o n of t he e ve nt. Use of resc ue t hera p y will be treate d statisticall y a s 
descri be d i n t he S A P. 
See Statistical C o nsi derati o ns, Secti o n  9,  f or i m plicati o ns of t he use of resc ue t hera p y a n d/ or 
ot her K +  bi n ders t o t he a nal ysis of e n d p oi nts. 
6. 5. 2  
Di al ys ate  P ot assi u m C o nce ntr ati o n Prescri pti o n  
T he dial ysate K +  c o nce ntrati o n prescri pti o n s h o ul d be rec or de d at t he ti mes i n dicate d i n t he 
Sc he d ule of Acti vities ( S o A ; see Ta ble  1). 
F or pre- dial ysis S- K +  c o nce ntrati o ns < 3. 5 m m ol/ L, s u bse q ue nt a dj ust me nts will be ma de i n 
acc or da nce t o l ocall y acce pte d cli nical practice patter ns a n d g ui de d b y t he i n vesti gat or’s 
cli nical j u d g me nt . 
F or ce ntres  t hat a d o pt t he cli nical practice of m o dif yi n g t he prescri be d dial ysate p otassi u m 

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3 0  of 8 2  
c o nce ntrati o n w he n t he pre- dial ysis ser u m p otassi u m c o nce ntrati o n decreases, if pre -dial ysis 
S- K +  is bel o w 3. 5 m m ol/ L t he dial ysate K +  c o nce ntrati o n s h o ul d be i ncrease d b y 0. 5 or 
1 m m ol/ L acc or di n g t o S o C, e g, i ncrease dial ysate K+  fr o m 1 K+  t o 1. 5 or 2 K+ , fr o m 2 K+  t o 2. 5 
or 3 K + , or fr o m 3 K+  t o 3. 5 or 4 K+ . 
6. 6  
D ose M o dific ati o n  
T he rec o m me n de d starti n g d ose is 5 g o nce dail y o n n o n- dial ysis da ys. To esta blis h 
n or m o kalae mia (i n t he ra n ge c o m m o nl y re gar de d as acce pta ble i n t hese patie nts [ 3. 5-
5. 5 m m ol/ L]) , t he d ose ma y be titrate d u p or d o w n wee kl y base d o n t he pre- dial ysis S- K+  
val ue after t he LI DI . T he d ose c o ul d be a dj uste d at i nter vals of 1 wee k i n i ncre me nts of 5 g u p 
t o 1 5 g o nce dail y o n n o n- dial ysis da ys. 
6. 7  
I nter ve nti o n After t he E n d of t he St u d y  
N o i nter ve nti o n will f oll o w t he e n d of t he st u d y. Decisi o n t o c o nti n ue o n S Z C treat me nt or 
S o C will be at i n vesti gat or’s discreti o n.  
7  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D 
P A R TI CI P A N T DI S C O N TI N U A TI O N/ WI T H D R A W A L  
7. 1  
Disc o nti n u ati o n of St u d y I nter ve nti o n 
It ma y be necessar y f or a partici pa nt t o per ma ne ntl y disc o nti n ue ( defi niti ve disc o nti n uati o n) 
st u d y i nter ve nti o n. If st u d y i nter ve nti o n is per ma ne ntl y disc o nti n ue d, t he partici pa nt will 
re mai n i n t he st u d y a n d c o m plete all e n d- of-treat me nt pr oce d ures. See t he S o A (Ta ble  1) f or 
data t o be c ollecte d at t he ti me of disc o nti n uati o n of st u d y i nter ve nti o n a n d f oll o w- u p a n d f or 
a n y f urt her e val uati o ns t hat nee d t o be c o m plete d. 
N ote t hat disc o nti n uati o n fr o m st u d y i nter ve nti o n is N O T t he sa me t hi n g as a wit h dra wal fr o m 
t he st u d y. 
To mi ni mi se ris k f or e ve nts relate d t o pr ol o n gati o n of Q Tc, t he f oll o wi n g disc o nti n uati o n 
criteria will be f oll o we d:  
•  
If a n a bs ol ute Q Tc F > 5 5 0 ms or a n i ncrease i n Q Tc F i nter val > 6 0 ms fr o m 
e nr ol me nt t o m ore t ha n 5 0 0 ms is reac he d , t he s u bject s h o ul d i m me diatel y 
recei ve a p pr o priate me dical i nter ve nti o n a n d be disc o nti n ue d fr o m t he st u d y 
dr u g treat me nt.  
•  
All partici pa nts meeti n g t he Q Tc F > 5 0 0 ms criteri o n s h o ul d i m me diatel y ha ve 
K +  assesse d, if n ot alrea d y d o ne wit hi n 1 h o ur of perf ormi n g t he E C G.  

Cli nical St u d y Pr ot oc ol  - 3. 0  
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3 1  of 8 2  
Ot her reas o ns f or disc o nti n uati o n of st u d y i nter ve nti o n ma y i ncl u de: 
•  
Partici pa nt decisi o n : T he partici pa nt is at a n y ti me free t o disc o nti n ue treat me nt, 
wit h o ut prej u dice t o f urt her treat me nt.  
•  
I nc orrectl y ra n d o mise d partici pa nt i n w h o m t he i ncl usi o n/e xcl usi o n criteria 
vi olati o n w o ul d p ut t he partici pa nt at u n d ue ris k. 
•  
A d verse e ve nt f or w hic h t he i n vesti gat or j u d ges c o nti n ue d treat me nt ma y p ut t he 
partici pa nt at u n d ue ris k. 
•  
Se vere n o nc o m plia nce wit h t he C S P . 
See t he S o A  (Ta ble  1) f or data t o be c ollecte d at t he ti me of i nter ve nti o n disc o nti n uati o n a n d 
f oll o w- u p a n d f or a n y f urt her e val uati o ns t hat nee d t o be c o m plete d . 
7. 1. 1  
Te m p or ar y Disc o nti n u ati o n  
I n hae m o dial ysis  patie n ts, if S- K +  is < 3. 0 m m ol/ L o n a n y n o n- dial ysis da y or pre-dial ysis , 
S Z C  a d mi nistrati o n s h o ul d be wit h hel d a n d h y p o kalae mia s h o ul d be ma na ge d as per sta n dar d 
practice. T he  partici pa nt  s h o ul d be e val uate d f or a n y i nterc urre nt ill ness or c o m or bi dit y t hat 
ma y i ncrease t he ris k of h y p o kalae mia. S Z C  a d mi nistrati o n ca n be res u me d if i n dicate d  b ut 
o nl y after t he i nterc urre nt me dical c o n diti o n  t hat preci pitate d t he h y p o kalae mia has i m pr o ve d 
a nd S- K +  has ret ur ne d t o t he tar get ra n ge of n or mal le vels ( 3. 5 – 5. 5 m m ol/ L).  
If partici pa nt  te m p oraril y disc o nti n ue st u d y i nter ve nti o n f or reas o ns ot her t ha n h y p o kalae mia, 
S Z C a d mi nistrati o n ca n be res u me d o nce partici pa nt c o n diti o n is sta bilis e d acc or di n g t o 
i n vesti gat or j u d ge me nt, a n d if t he partici pa nt  is willi n g to ta ke treat me nt.  
7. 2  
P artici p a nt Wit h dr a w al fr o m t he St u d y  
•  
A partici pa nt ma y wit h dra w fr o m t he st u d y at a n y ti me at his/ her o w n re q uest, or ma y be 
wit h dra w n at a n y ti me at t he discreti o n of t he i n vesti gat or f or safet y, be ha vi o ural, 
c o m plia nce, or a d mi nistrati ve reas o ns. T his is e x pecte d t o be u nc o m m o n. 
•  
A partici pa nt w h o c o nsi ders wit h dra wi n g fr o m t he st u d y m ust be i nf or me d b y t he 
i n vesti gat or a b o ut m o difie d f oll o w- u p o pti o ns (e g, tele p h o ne c o ntact, a c o ntact wit h a 
relati ve or treati n g p h ysicia n, or i nf or mati o n fr o m me dical rec or ds). 
•  
At t he ti me of wit h dra wal fr o m t he st u d y, if p ossi ble, a n Earl y Disc o nti n uati o n visit 
s h o ul d be c o n d ucte d, as s h o w n i n t he S o A ( Ta ble 1) f or data t o be c ollecte d at t he ti me of 
st u d y wit h dra wal a n d f oll o w- u p a n d f or a n y f urt her e val uati o ns t hat nee d t o be 
c o m plete d. 
− 
T he partici pa nt will disc o nti n ue t he st u d y i nter ve nti o n a n d be wit h dra w n fr o m t he 
st u d y at t hat ti me. 
•  
If t he partici pa nt wit h dra ws c o nse nt f or discl os ure of f ut ure i nf or mati o n, t he s p o ns or ma y 
retai n a n d c o nti n ue t o use a n y data c ollecte d bef ore s uc h a wit h dra wal of c o nse nt. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 2  of 8 2  
•  
If a partici pa nt wit h dra ws fr o m t he st u d y, it s h o ul d be c o nfir me d if he/s he still a grees f or 
e xisti n g sa m ples t o be use d i n li ne wit h t he ori gi nal c o nse nt. If he/s he re q uests wit h dra wal 
of c o nse nt f or use of sa m ples, destr ucti o n of a n y sa m ples ta ke n a n d n ot teste d s h o ul d be 
carrie d o ut i n li ne wit h w hat was state d i n t he i nf or me d c o nse nt a n d l ocal re g ulati o n. T he 
i n vesti gat or m ust d oc u me nt t he decisi o n o n use of e xisti n g sa m ples i n t he site st u d y 
rec or ds a n d i nf or m t he Gl o bal St u d y Tea m. 
7. 3  
L ost t o F oll o w - u p 
A partici pa nt  will be c o nsi dere d l ost t o f oll o w- u p if he or s he re peate dl y fails t o ret ur n f or 
sc he d ule d visits a n d is u na ble t o be c o ntacte d b y t he st u d y site. 
T he f oll o wi n g acti o ns m ust be ta ke n if a partici pa nt fails t o ret ur n t o t he cli nic f or a re q uire d 
st u d y visit: 
•  
T he site m ust atte m pt t o c o ntact t he partici pa nt a n d resc he d ule t he misse d visit as s o o n as 
p ossi ble a n d c o u nsel t he partici pa nt o n t he i m p orta nce of mai ntai ni n g t he assi g ne d visit 
sc he d ule a n d ascertai n w het her or n ot t he partici pa nt wis hes t o a n d/ or s h o ul d c o nti n ue i n 
t he st u d y. 
•  
Bef ore a partici pa nt is dee me d l ost t o f oll o w - u p, t he i n vesti gat or or desi g nee m ust ma ke 
e ver y eff ort t o re gai n c o ntact wit h t he partici pa nt ( w here p ossi ble, 3 tele p h o ne calls a n d, 
if necessar y, a certifie d letter t o t he partici pa nt’s last k n o w n maili n g a d dress or as per 
l ocall y all o we d re g ulati o ns). T hese c o ntact atte m pts s h o ul d be d oc u me nte d i n t he 
partici pa nt’s me dical rec or d.  
•  
S h o ul d t he partici pa nt c o nti n ue t o be u nreac ha ble, he/s he will be c o nsi dere d t o ha ve 
wit h dra w n fr o m t he st u d y. 
Disc o nti n uati o n of s pecific sites or of t he st u d y as a w h ole are ha n dle d as part of  A p pe n di x A.  
8  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  
•  
St u d y pr oce d ures a n d t heir ti mi n g are s u m marise d i n t he S o A (Ta ble  1). Pr ot oc ol wai vers 
or e xe m pti o ns are n ot all o we d. 
•  
I m me diate safet y c o ncer ns s h o ul d be disc usse d wit h t he s p o ns or i m me diatel y u p o n 
occ urre nce or a ware ness t o deter mi ne if t he partici pa nt s h o ul d c o nti n ue or disc o nti n ue 
st u d y i nter ve nti o n. 
•  
A d here nce t o t he st u d y desi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he S o A 
(Ta ble  1), is esse ntial a n d re q uire d f or st u d y c o n d uct. 
•  
A ll scree ni n g e val uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial 
partici pa nts meet all eli gi bilit y criteria. T he i n vesti gat or will mai ntai n a scree ni n g l o g t o 
rec or d details of all partici pa nts scree ne d a n d t o c o nfir m eli gi bilit y or rec or d reas o ns f or 
scree ni n g fail ure, as a p plica ble. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 3  of 8 2  
•  
Pr oce d ures c o n d ucte d as part of t he partici pa nt’s r o uti ne cli nical ma na ge me nt (e g, bl o o d 
c o u nt) a n d o btai ne d bef ore si g ni n g of t he I C F ma y be utilise d f or scree ni n g or baseli ne 
p ur p oses pr o vi de d t he pr oce d ures met t he pr ot oc ol- s pecifie d criteria a n d were perf or me d 
wit hi n t he ti me fra me defi ne d i n t he S o A  (Ta ble  1). 
8. 1  
Effic ac y Assess me nts  
8. 1. 1  
P ot assi u m  
P otassi u m will be meas ure d after LI DI a n d after vital si g ns , E C G , a n d p h ysical e xa mi nati o n . 
Ser u m sa m ples will be a nal yse d usi n g l ocal la b orat or y f or t he p ur p oses of st u d y i ncl usi o n a n d 
m o nit ori n g.  
All ser u m sa m ples s h o ul d be e xa mi ne d a n d a n y o vertl y hae m ol yse d sa m ples m ust be re dra w n.  
See t he la b orat or y ma n ual f or details o n dra wi n g, pre parati o n, a n d a nal ysis of bl o o d sa m ples. 
8. 1. 2  
P atie nt -Re p orte d O utc o mes  ( P R Os) 
P R Os refer t o all o utc o mes a n d s y m pt o ms t hat are directl y re p orte d b y t he partici pa nt . P R Os 
ha ve bec o me i m p orta nt e n d p oi nts f or re g ulat or y a n d rei m b urse me nt a ut h orities w he n 
e val uati n g effecti ve ness of treat me nts i n cli nical trials.  
T he f oll o wi n g P R Os will be a d mi nistere d i n t he st u d y: K D Q O L - 3 6, E Q - 5 D- 5 L, T S Q M - 9, a n d 
P GI C  (refer t o A p pe n di x C ). Partici pa nts will be as ke d t o c o m plete t he q uesti o n naires i n a n 
electr o nic de vice at site visits s pecifie d i n t he S o A (Ta ble  1). 
8. 1. 2. 1  
K D Q O L ™- 3 6 
T he K D Q O L - 3 6 is a vali date d, self-re p orte d q uesti o n naire t hat c o m bi nes ge neric a n d 
disease -s pecific c o m p o ne nts f or assessi n g s y m pt o ms a n d healt h-relate d q ualit y of life 
( H R Q o L) of patie nts wit h C K D, see A p pe n di x  C 1 (Ricar d o et al . 2 0 1 3). T he K D Q O L- 3 6 
c o m prises a P C S (1 2 ite ms) , M C S (1 2 ite ms) , S y m pt o ms/ Pr o ble ms ( 1 2 ite ms) , B ur de n of 
Ki d ne y Disease ( 4 ite ms) , a n d Effects of Ki d ne y Disease ( 8 ite ms). Hi g her sc ores i n dicate 
better healt h/ H R Q ol. 
8. 1. 2. 2  
E Q - 5 D- 5 L 
T he E Q - 5 D-5 L is a self-re p orte d q uesti o n naire t hat is use d t o deri ve a sta n dar dise d meas ure of 
healt h stat us, als o referre d t o as a utilit y sc ore (refer t o A p pe n di x  C 2 [Her d ma n et al. 2 0 1 1 ]). 
E Q - 5 D-5 L utilit y sc ores are wi del y acce pte d b y rei m b urse me nt a ut h orities a n d will be use d t o 
s u p p ort healt h ec o n o mic e val uati o ns. 
8. 1. 2. 3  
T S Q M - 9 
T he T S Q M - 9 is a patie nt -re p orte d i nstr u me nt t o assess patie nts’ satisfacti o n wit h me dicati o n, 
pr o vi di n g sc ores o n 3 scales: effecti ve ness ( 3 ite ms), c o n ve nie nce ( 3 ite ms), a n d gl o bal 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 4  of 8 2  
satisfacti o n ( 3 ite ms) (see A p pe n di x C 3). T he T S Q M - 9 d o mai n sc ores ra n ge fr o m 0 t o 1 0 0 
wit h hi g her sc ores re prese nti n g hi g her satisfacti o n o n t hat d o mai n . T S Q M- 9 is a n a b bre viate d 
versi o n deri ve d fr o m t he T S Q M versi o n 1. 4 a n d has s h o w n g o o d ps yc h o metric pr o perties 
( B har mal et al. 2 0 0 9). 
8. 1. 2. 4  
P GI C  
T he P GI C will be i ncl u de d t o assess h o w a patie nt percei ves his/ her c ha n ge i n acti vit y 
li mitati o ns, s y m pt o ms, e m oti o ns, a n d o verall H R Q o L  si nce t he start of st u d y treat me nt (see 
A p pe n di x  C 4 ). 
8. 1. 2. 5  
A d mi nistr ati o n of Electr o nic P at ie nt-Re p orte d O utc o mes (e P R Os)  
T he f oll o wi n g best practice s h o ul d be f oll o we d: 
•  
All P R O q uesti o n naires m ust be c o m plete d b y partici pa nts at site usi n g a n electr o nic 
de vice; pa per q uesti o n naires are n ot all o we d i n t his st u d y. 
•  
Eac h site m ust all ocate t he res p o nsi bilit y f or t he a d mi nistrati o n of t he e P R Os t o a s pecific 
i n di vi d ual a n d, if p ossi ble, assi g n a bac k u p pers o n t o c o ver if t hat i n di vi d ual is a bse nt. 
•  
A ke y as pect of st u d y s uccess is t o ha ve hi g h P R O c o m plia nce. T heref ore, it is esse ntial 
t hat site pers on nel f oll o w t he S o A (Ta ble  1) a n d e ns ure t hat t he de vice is c har ge d a n d set 
u p pr o perl y bef ore t he first partici pa nt atte n ds visit 1, i n or der t o mi ni mise missi n g data. 
•  
It is rec o m me n de d t hat t he e P R O q uesti o n naires are co m plete d bef ore a n y ot her st u d y 
pr oce d ures are c o n d ucte d, i ncl u di n g bei n g see n b y t he i n vesti gat or. 
•  
T o a v oi d bias partici pa nts m ust n ot recei ve hel p fr o m relati ves, frie n ds , or site staff t o 
a ns wer or t o clarif y t he e P R O q uesti o n naires a n d m ust be c o m plete d b y t he partici pa nt i n 
pri vate.  
•  
T he a p p oi nte d site pers o n nel s h o ul d e x plai n t o partici pa nts t he val ue a n d rele va nce of 
e P R O assess me nts a n d i nf or m t hat t hese q uesti o ns are bei n g as ke d t o fi n d o ut, directl y 
fr o m partici pa nts, h o w he/s he feels. 
•  
T he a p p oi nte d site pers o n nel m ust s h o w partici pa nts h o w t o use t he e P R O de vice, i n 
acc or da nce wit h t he i nstr ucti o ns pr o vi de d.  
•  
If t he partici pa nt is u na ble t o rea d t he q uesti o n naire (e g, is bli n d or illiterate), t he 
partici pa nt is e xe m pte d fr o m c o m pleti n g t he e P R O q uesti o n naires b ut ma y still partici pate 
i n t he st u d y. Partici pa nt s e xe m pte d i n t his re gar d s h o ul d be fla g ge d a p pr o priatel y b y t he 
site staff i n t he s o urce d oc u me nts a n d i n e C R F. 
•  
If a partici pa nt uses vis ual ai ds (e g, s pectacles or c o ntact le nses) f or rea di n g a n d d oes n ot 
ha ve t he m at ha n d, t he partici pa nt will be e xe m pte d fr o m c o m pleti n g t he P R Os 
q uesti o n naires o n t hat visit. Partici pa nt s e xe m pte d i n t his re gar d s h o ul d be fla g ge d 
a p pr o priatel y b y site t he staff i n s o urce d oc u me nts a n d i n t he e C R F. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 5  of 8 2  
•  
T he researc h n urse or a p p oi nte d site staff s h o ul d stress t hat t he i nf or mati o n is n ot 
r o uti nel y s hare d wit h st u d y staff. T heref ore, if t he partici pa nt has a n y me dical pr o ble ms, 
t he y s h o ul d disc uss t he m wit h t he d oct or or researc h n urse se paratel y fr o m t he e P R O 
assess me nt. 
•  
Site staff m ust a d mi nister q uesti o n naires a vaila ble i n t he la n g ua ge t hat t he partici pa nt 
s pea ks a n d u n dersta n ds. Q uesti o ns s h o ul d n ot be rea d i n a n a vaila ble la n g ua ge a n d 
tra nslate d i nt o a n ot her la n g ua ge f or t he partici pa nt. 
•  
O n c o m pleti o n of t he q uesti o n naires, t he ta blet s h o ul d be ha n de d bac k t o t he desi g nate d 
res p o nsi ble pers o n w h o s h o ul d c hec k t hat all q uesti o n naires rele va nt f or t he s pecific visit 
were c o m plete d. If a n y P R O q uesti o n naire was n ot c o m plete d, t he site pers o n nel m ust 
d oc u me nt t h e reas o n w h y a partici pa nt c o ul d n ot c o m plete assess me nts i n s o urce 
d oc u me nts a n d t he R E V P R DI m o d ule i n t he e C R F. 
8. 2  
S afet y Assess me nts  
Pla n ne d ti me p oi nts f or all safet y assess me nts are pr o vi de d i n t he S o A (Ta ble  1). 
8. 2. 1  
P h ysic al E x a mi n ati o ns  
A brief p h ysical e xa mi nati o n will i ncl u de, at a mi ni m u m, assess me nts of t he s ki n, l u n gs, 
car di o vasc ular s yste m, a n d a b d o me n (li ver a n d s plee n).  Hei g ht, lea n wei g ht, a n d trice ps 
s ki n-f ol d t hic k ness assess me nts will als o be ma de at t he ti mes s pecifie d i n t he S o A (Ta ble  1). 
P h ysical e xa mi nati o n will be perf or me d at ti me p oi nts as s pecifie d i n t he S o A (Ta ble  1). 
8. 2. 2  
Vit al Si g ns  
Vital si g ns  ( bl o o d press ure, p ulse rate, a n d oral te m perat ure) will be perf or me d at ti me p oi nts 
as s pecifie d i n t he S o A (Ta ble  1), after 5 mi n of l yi n g or sitti n g d o w n wit h o ut a n y distracti o ns. 
8. 2. 3  
Electr oc ar di o gr a ms  
A n E C G will be perf or me d at ti me p oi nts s pecifie d i n t he S o A  (Ta ble  1). Q Tc( F) s h o ul d be 
rec or de d at eac h E C G meas ure me nt. E C G data a n d S- K +  val ues s h o ul d be c ollecte d a n d 
rec or de d i n t he e C R F i n c o n necti o n wit h re p orti n g A Es of S- K+  bel o w 3. 0 m m ol/ L . 
St u d y s u bjects wit h pace ma kers: 
•  
All E C G varia bles, i ncl u di n g Q T/ Q Tc( F), s h o ul d be rea d ma n uall y  a n d rec or de d i n t he 
e C R F.  
•  
If n ot f ulfilli n g t he i ncl usi o n/e xcl usi o n criteria or f ulfilli n g t he disc o nti n uati o n criteria, 
pace ma ker partici pa nt s s h o ul d be ma na ge d as rec o m me n de d b y pr ot oc ol ( wit h o ut 
e xce pti o ns). 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 6  of 8 2  
8. 2. 4  
Cli nic al S afet y L a b or at or y Assess me nts  
Bl o o d sa m ples f or deter mi nati o n of cli nical c he mistr y  a n d hae mat ol o g y will be ta ke n bef ore 
dial ysis at t he visits  i n dicate d i n t he S o A (Ta ble  1). 
A d diti o nal safet y sa m ples ma y be c ollecte d if cli nicall y i n dicate d at t he discreti o n of t he 
i n vesti gat or. T he date, ti me of c ollecti o n , a n d res ults ( val ues, u nits , a n d refere nce ra n ges) will  
be rec or de d o n t he a p pr o priate e C R F. 
T he cli nical c he mistr y  a n d hae mat ol o g y will be perf or me d at a l ocal la b orat or y at or near t o 
t he i n vesti gat or site. Sa m ple t u bes a n d sa m ple sizes ma y var y de pe n di n g o n la b orat or y 
met h o d use d a n d r o uti ne practice at t he site. 
T he f oll o wi n g la b orat or y varia bles will be meas ure d.  
Ta b le 5  
La b or at or y S afet y Vari a bles  
H ae m at ol o g y/ H ae m ost asis ( w h ole bl o o d)  
Cli nic al C he mistr y (ser u m or pl as m a)  
B- Hae m o gl o bi n ( H b)  
S/ P -Creati ni ne   
B- Le u k oc yte c o u nt  
Bl o o d urea nitr o ge n ( B U N)  
B- Le u k oc yte differe ntial c o u nt (a bs ol ute c o u nt)  
S/ P -Bilir u bi n, t otal  
B -Platelet c o u nt  
S/ P -Al kali ne p h os p hatase ( A L P) 
 
S/ P -As partate tra nsa mi nase ( A S T)  
 
S/ P Ga m ma -gl uta m yl tra nsferase ( G G T)  
 
S/ P -Al b u mi n  
 
S/ P- Lactate d e h y dr o ge nase  
 
S- K +  
 
S- calci u m  
 
S- ma g nesi u m  
 
S-s o di u m  
 
S -p h os p hate  
 
S- bicar b o nate  
 
S/ P- C hl ori de  
 
S/ P- Gl uc ose  
 
S/ P -Creati ne ki nase ( C K)  
 
S/ P- T otal pr otei n  
 
S- Pre g na nc y test (ser u m h C G)  
A b bre viati o ns: B = bl o o d; h C G = h u ma n c h ori o nic g o na d otr o pi n; P = plas ma; S = ser u m.  

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 7  of 8 2  
8. 2. 5  
Ot her Assess me nts  
8. 2. 5. 1  
Di al ysis Prescri pti o n  
Dial ysis prescri pti o n para meters i ncl u di n g bl o o d fl o w ( Q b, m L / mi n) a n d ti me o n dial ysis 
( mi n utes) s h o ul d be rec or de d at t he ti mes s pecifie d i n Ta ble  1. 
8. 2. 5. 2  
Di al ysis A de q u ac y  
Dial ysis a de q uac y i n dices i ncl u di n g s p Kt/ V a n d/ or urea re d ucti o n rati o ( U R R ) s h o ul d be 
rec or de d at t he ti mes s pecifie d i n Ta ble  1. I n vesti gat ors s h o ul d rec or d t he m ost rece nt val ues 
b ut t hese s h o ul d be n o ol der t ha n 5 wee ks. If n o val ues wit hi n 5 wee ks are a vaila ble, a ne w 
assess me nt of s p Kt/ V a n d/ or U R R s h o ul d be perf or me d o n t he ne xt wee kl y visit. Sites s h o ul d 
c o nsiste ntl y use eit her s p Kt/ V or U R R i n deter mi ni n g dial ysis a de q uac y. A c o m bi nati o n of 
b ot h is n ot acce pta ble.  
8. 2. 5. 3  
I nter di al ytic W ei g ht G ai n (I D W G) 
I D W G will be calc ulate d as t he differe nce bet wee n c urre nt pre - dial ysis wei g ht mi n us pre vi o us 
p ost- dial ysis wei g ht ( meas ure d at i m me diate dial ysis sessi o n pri or t o t he visit) i n kil o gra ms. 
I n or der t o o btai n all re q uire d meas ure me nts of I D W G t he i n vesti gat ors m ust ma ke s ure t hat a 
p ost- dial ysis wei g ht is a vaila ble f or t he i m me diate dial ysis sessi o n (as per us ual sc he d ule) 
pri or t o t he visit . 
8. 3  
A d verse E ve nts  a n d  Seri o us A d verse E ve nts  
T he pri nci pal i n vesti gat or  is res p o nsi ble f or e ns uri n g t hat all staff i n v ol ve d i n t he st u d y are 
fa miliar wit h t he c o nte nt of t his secti o n. 
T he defi niti o ns of a n A E or S A E ca n be f o u n d i n  A p pe n di x B. 
A d verse e ve nts will be re p orte d b y t he partici pa nt  ( or, w he n a p pr o priate, b y a care gi ver, 
s urr o gate, or t he partici pa nt 's le gall y a ut h orise d re prese ntati ve).  
T he i n vesti gat or a n d a n y desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d rec or di n g 
e ve nts t hat meet t he defi niti o n of a n A E . 
8. 3. 1  
Ti me Peri o d a n d Fre q ue nc y f or C ollecti n g A E a n d S A E 
I nf or m ati o n 
A d verse eve nts will be c ollecte d fr o m t he first d ose of S Z C, t hr o u g h o ut t he st u d y, a n d d uri n g 
t he f oll o w- u p peri o d, descri be d earlier. 
S A Es  will be rec or de d fr o m t he ti me of si g ni n g of  t he I C F. 
If t he i n vesti gat or bec o mes a ware of an S A E  wit h a s us pecte d ca usal relati o ns hi p t o t he 
i n vesti gati o nal me dici nal pr o d uct t hat occ urs after t he e n d of t he cli nical st u d y i n a partici pa nt  

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 8  of 8 2  
treate d b y hi m or her, t he i n vesti gat or s hall, wit h o ut u n d ue dela y, re p ort t he S A E  t o t he 
s p o ns or. 
8. 3. 2  
F oll o w -u p of A Es a n d S A Es  
A n y A Es t hat are u nres ol ve d at t he f oll o w- u p visit i n t he st u d y are f oll o we d u p b y t he 
i n vesti gat or f or as l o n g as me dicall y i n dicate d, b ut wit h o ut f urt her rec or di n g i n t he eC R F . 
Astra Ze neca retai ns t he ri g ht t o re q uest a d diti o nal i nf or mati o n f or a n y partici pa nt  wit h 
o n g oi n g A E(s)/ S A E(s) at t he e n d of t he st u d y, if j u d ge d necessar y. 
A d verse e ve nt v ari a bles  
T he f oll o wi n g varia ble s will be c ollecte d f or eac h A E: 
•  
A E ( ver bati m)  
•  
T he date w he n t he A E starte d a n d st o p pe d  
•  
Ma xi m u m A E i nte nsit y ( mil d, m o derate, se vere)  
•  
W het her t he A E is seri o us or n ot 
•  
I n vesti gat or ca usalit y rati n g a gai nst t he i n vesti gati o nal pr o d uct ( yes or n o) 
•  
Acti o n ta ke n wit h re gar d t o i n vesti gati o nal pr o d uct 
•  
O utc o me. 
I n a d diti o n, t he f oll o wi n g varia bles will be c ollecte d f or S A Es:  
•  
Date A E met criteria f or S A E  
•  
Date i n vesti gat or beca me a ware of S A E  
•  
A E is seri o us d ue t o  
o  
Res ults i n deat h  
o  
Is i m me diatel y life-t hreate ni n g 
o  
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  
o  
Res ults i n persiste nt or si g nifica nt disa bilit y/i nca pacit y or s u bsta ntial disr u pti o n 
of t he a bilit y t o c o n d uct n or mal life f u ncti o ns  
o  
Is or res ults i n a c o n ge nital a n o mal y or birt h defect 
o  
Is a n i m p orta nt me dical e ve nt t hat ma y je o par dise t he partici pa nt or ma y re q uire 
me dical i nter ve nti o n t o pre ve nt o ne of t he o utc o mes liste d a b o ve 
•  
Date of h os pitalisati o n  
•  
Date of disc har ge 
•  
Pr o ba ble ca use of deat h 
•  
Date of deat h  
•  
A ut o ps y perf or me d 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
3 9  of 8 2  
•  
Ca usalit y assess me nt i n relati o n t o st u d y pr oce d ure(s)  
•  
Ca usalit y assess me nt t o ot her me dicati o n . 
8. 3. 3  
C a us alit y  Collecti o n  
T he i n vesti gat or will  assess ca usal relati o ns hi p bet wee n i n vesti gati o nal pr o d uct a n d eac h A E , 
a n d a ns wer ‘ yes’ or ‘ n o’ t o t he q uesti o n ‘ D o y o u c o nsi der t hat t here is a reas o na ble p ossi bilit y 
t hat t he e ve nt ma y ha ve bee n ca use d b y t he i n vesti gati o nal pr o d uct?’ 
F or S A Es, ca usal relati o ns hi p s h o ul d als o be assesse d f or ot her me dicati o n a n d st u d y 
pr oce d ur es. N ote t hat f or S A Es t hat c o ul d be ass ociate d wit h a n y st u d y pr oce d ure, t he ca usal 
relati o ns hi p is i m plie d as ‘ yes’. 
A g ui de t o t he i nter pretati o n of t he ca usalit y q uesti o n is f o u n d i n  A p pe n di x B t o t he CS P. 
8. 3. 4  
A d verse E ve nts B ase d o n S i g ns a n d S y m pt o ms  
All A Es s p o nta ne o usl y re p orte d b y t he partici pa nt  or re p orte d i n res p o nse t o t he o pe n q uesti o n 
fr o m t he st u d y site staff: ‘ Ha ve y o u ha d a n y healt h pr o ble ms si nce t he pre vi o us visit/ y o u were 
last as ke d?’, or re veale d b y o bser vati o n will be c ollecte d a n d rec or de d i n t he eC R F . W he n 
c ollecti n g A Es, t he rec or di n g of dia g n oses is preferre d ( w he n p ossi ble) t o rec or di n g a list of 
si g ns a n d s y m pt o ms. H o we ver, if a dia g n osis is k n o w n a n d t here are ot her si g ns or s y m pt o ms 
t hat are n ot ge nerall y part of t he dia g n osis, t he dia g n osis a n d eac h si g n or s y m pt o m will be 
rec or de d se paratel y. 
8. 3. 5  
A d verse E ve nts B ase d o n E x a mi n ati o ns a n d Tests  
T he res ults fr o m t he C S P -ma n date d la b orat or y tests a n d vital si g ns will be s u m marise d i n t he 
Cli nical St u d y Re p ort . 
Deteri orati o n as c o m pare d t o baseli ne i n C S P - ma n date d la b orat or y val ues, vital si g ns , a n d 
E C Gs  s h o ul d t heref ore o nl y be re p orte d as A Es if t he y f ulfil a n y of t he S A E criteria, are t he 
reas o n f or disc o nti n uati o n of treat me nt wit h t he i n vesti gati o nal pr o d uct, or are c o nsi dere d t o 
be cli nicall y rele va nt as j u d ge d b y t he i n vest i gat or ( w hic h ma y i ncl u de b ut n ot li mite d t o 
c o nsi derati o n as t o w het her treat me nt or n o n -pla n ne d visits were re q uire d or ot her acti o n was 
ta ke n wit h t he st u d y i nter ve nti o n, e g, d ose a dj ust me nt or dr u g i nterr u pti o n). 
If deteri orati o n i n a la b orat or y val ue/ vital si g n is ass ociate d wit h cli nical si g ns a n d s y m pt o ms, 
t he si g n or s y m pt o m will be re p orte d as a n A E a n d t he ass ociate d la b orat or y res ult/ vital si g n 
will be c o nsi dere d as a d diti o nal i nf or mati o n . W here ver p ossi ble t he re p orti n g i n vesti gat or 
uses t he cli nical, rat her t ha n t he la b orat or y ter m ( e g, a nae mia vers us l o w hae m o gl o bi n val ue) . 
I n t he a bse nce of cli nical si g ns or s y m pt o ms, cli nicall y rele va nt deteri orati o ns i n 
n o n- ma n date d para meters s h o ul d be re p orte d as A E(s). 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 0  of 8 2  
Deteri orati o n of a la b orat or y val ue, w hic h is u ne q ui v ocall y d ue t o disease pr o gressi o n, s h o ul d 
n ot be re p orte d as a n A E/ S A E. 
A n y ne w or a g gra vate d cli nicall y rele va nt a b n or mal me dical fi n di n g at a p h ysical e xa mi nati o n 
as c o m pare d wit h t he baseli ne assess me nt will be re p orte d as a n A E u nless u ne q ui v ocall y 
relate d t o t he disease u n der st u d y. 
8. 3. 6  
Re p orti n g of S eri o us A d verse E ve nts  
All S A Es ha ve t o be re p orte d, w het her or n ot c o nsi dere d ca usall y relate d t o t he i n vesti gati o nal 
pr o d uct, or t o t he st u d y pr oce d ure(s). All S A Es will be rec or de d i n t he eC R F.  
If a n y S A E occ urs i n t he c o urse of t he st u d y, i n vesti gat ors or ot her site pers o n nel will i nf or m 
t he a p pr o priate Astra Ze neca re prese ntati ves wit hi n 1 da y, ie, i m me diatel y b ut n o l ater t h a n 
2 4 h o urs of w he n he or s he be c o mes a ware of it . 
T he desi g nate d Astra Ze neca re prese ntati ve will w or k wit h t he i n vesti gat or  t o e ns ure t hat all 
t he necessar y i nf or mati o n is pr o vi de d t o t he Astra Ze neca Patie nt Safet y data e ntr y site wit hi n 
1  c ale n d ar d a y  of i nitial recei pt f or fatal a n d life-t hreate ni n g e ve nts a n d wit hi n 5 c ale n d ar  
d a ys of i nitial recei pt f or all ot her S A Es.  
F or fatal or life -t hreate ni n g A E s w here i m p orta nt or rele va nt i nf or mati o n is missi n g, acti ve 
f oll o w- u p will be u n derta ke n i m me diatel y. I n vesti gat ors or ot her site pers o n nel will i nf or m 
Astra Ze neca re prese ntati ves of a n y f oll o w - u p i nf or mati o n o n a pre vi o usl y re p orte d S A E 
wit hi n 1 cale n dar  da y, ie, i m me diatel y b ut n o l ater t h a n 2 4 h o urs of w he n he or s he bec o mes 
a ware of it. 
O nce t he i n vesti gat ors or ot her site pers o n nel i n dicate a n A E is seri o us i n t he electr o nic data 
ca pt ure ( E D C ) s yste m, a n a ut o mate d e mail alert is se nt t o t he desi g nate d Astra Ze neca 
re prese ntati ve. 
If t he E D C s yste m is n ot a vaila ble, t he n t he i n vesti gat or or ot her st u d y site staff re p orts an 
S A E t o t he a p pr o priate Astra Ze neca re prese ntati ve b y tele p h o ne.  
T he Astra Ze neca re prese ntati ve will a d vise t he i n vesti gat or/st u d y site staff h o w t o pr ocee d. 
F or f urt her g ui da nce o n t he defi niti o n of a S A E, see  A p pe n di x B of t he C S P . 
T he refere nce d oc u me nt f or defi niti o n of e x pecte d ness/liste d ness is t he I B f or t he Astra Ze neca 
dr u g. 
8. 3. 7  
Pre g n a nc y  
A ser u m pre g na nc y test i n dial ysis patie nts ca n res ult i n false p ositi ve or i n deter mi nate 
o utc o mes, li kel y d ue t o cleara nce of t he h or m o ne h u ma n c h ori o nic g o na d otr o pi n ( h C G ). I n a 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 1  of 8 2  
real pre g na nc y, h C G le vels us ual d o u ble e ver y 2- 3 da ys. A re peat h C G test will be re q uire d 
± 1- 2 wee ks after t he 1 st assess me nt t o o bser ve t he tre n d. A false -p ositi ve 1 st res ult will yiel d 
si milar res ults i n t he 2 n d test. I n case of d o u bt a n ultras o u n d s h o ul d be c o nsi dere d t o e xcl u de 
a n y pre g na nc y, per t he discreti o n of t he i n vesti gat or. 
All pre g na ncies a n d o utc o mes of pre g na nc y s h o ul d be re p orte d t o Astra Ze neca e xce pt f or:  
•  If t he pre g na nc y is disc o vere d bef ore t he st u d y partici pa nt  has recei ve d a n y st u d y 
i nter ve nti o n 
•  Pre g na ncies i n t he part ner of male partici pa nts . 
If a n y pre g na nc y occ urs i n t he c o urse of t he st u d y ( partici pa nt-re p orte d), t he n t he i n vesti gat or 
or ot her site pers o n nel i nf or ms t he a p pr o priate Astra Ze neca re prese ntati ves wit hi n 1 da y, ie, 
i m me diatel y b ut n o later t ha n 2 4 h o urs of w he n he or s he bec o mes a ware of it. 
8. 3. 7. 1  
M ater n al E x p os ure  
Wo me n of c hil d beari n g p ote ntial are n ot all o we d t o be i ncl u de d i n t his st u d y u nless usi n g 
acce pta ble met h o ds of c o ntrace pti o n . S h o ul d a pre g na nc y still occ ur, t he i n vesti gati o nal 
pr o d uct s h o ul d be disc o nti n ue d i m me diatel y a n d t he pr e g na nc y re p orte d t o Astra Ze neca  
wit hi n 1 d a y , ie, i m me diatel y b ut n o l ater t h a n 2 4 h o urs of w he n he or s he bec o mes a ware of 
it. 
Pre g na nc y itself is n ot re gar de d as a n A E  u nless t here is a s us pici o n t hat t he i n vesti gati o nal 
pr o d uct u n der st u d y ma y ha ve i nterfere d wit h t he effecti ve ness of a c o ntrace pti ve me dicati o n. 
C o n ge nital a n o malies/ birt h defects a n d s p o nta ne o us miscarria ges s h o ul d be re p orte d a n d 
ha n dle d as S A Es. Elec ti ve a b orti o ns wit h o ut c o m plicati o ns s h o ul d n ot be ha n dle d as A Es. T he 
o utc o me of all pre g na ncies (s p o nta ne o us miscarria ge, electi ve ter mi nati o n, ect o pic pre g na nc y, 
n or mal birt h , or c o n ge nital a n o mal y) s h o ul d be f oll o we d u p a n d d oc u me nte d e ve n if t he 
parti ci pa nt was disc o nti n ue d fr o m t he st u d y. 
T he desi g nate d Astra Ze neca re prese ntati ve w or ks wit h t he i n vesti gat or t o e ns ure t hat all 
rele va nt i nf or mati o n is pr o vi de d t o t he Astra Ze neca Patie nt Safet y data e ntr y site wit hi n 1 or 
5 c ale n d ar d a ys  f or S A Es (see Secti o n 8. 3. 6) a n d wit hi n 3 0 d a ys  f or all ot her pre g na ncies. 
T he sa me ti meli nes a p pl y w he n o utc o me i nf or mati o n is a vaila ble.  
T he P R E G R E P m o d ule is use d t o re p ort t he pre g na nc y a n d t he P R E G O U T m o d ule is use d t o 
re p ort t he o utc o me of t he pre g na nc y. 
8. 3. 7. 2  
P ater n al E x p os ure  
T here is n o restricti o n o n fat heri n g c hil dre n or d o nati n g s per m d uri n g t he st u d y. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 2  of 8 2  
8. 3. 8  
Me dic ati o n E rr or 
F or t he p ur p oses of re p orti n g i n Astra Ze neca  cli nical st u dies, a me dicati o n err or  is a n 
u ni nte n de d de viati o n fr o m t he all o wa ble sc he d ule as per pr ot oc ol i n a d mi nisteri n g a n y st u d y 
dr u g t hat eit her ca uses har m t o t he partici pa nt or has t he p ote ntial t o ca use har m t o t he 
partici pa nt . 
If a me dicati o n err or occ urs i n t he c o urse of t he st u d y, t he n t he i n vesti gat or or ot her site 
pers o n nel i nf or ms t he a p pr o priate Astra Ze neca re prese ntati ves wit hi n 1 d a y , ie, i m me diatel y 
b ut n o l ater t h a n 2 4 h o urs  of w he n he or s he bec o mes a ware of it.  
T he desi g nate d Astra Ze neca re prese ntati ve w or ks wit h t he i n vesti gat or t o e ns ure t hat all 
rele va nt i nf or mati o n is c o m plete d wit hi n 1  (I nitial Fatal/ Life-T hreate ni n g or f oll o w -u p 
Fatal/ Life - T hreate ni n g) or 5  ( ot her seri o us i nitial a n d f oll o w- u p) c ale n d ar d a ys  if t here is a n 
S A E ass ociate d wit h t he me dicati o n err or (see Secti o n  8. 3. 6 ) a n d wit hi n 3 0 d a ys  f or all ot her 
me dicati o n err ors.  
T he defi niti o n of a Me dicati o n Err or ca n be f o u n d i n A p pe n di x  B 4. 
8. 4  
O ver d ose  
F or t his st u d y, a n y d ose of S Z C greater t ha n 1 5 g per da y o n n o n- dial ysis da ys will be 
c o nsi dere d a n o ver d ose. Treat me nt wit h S Z C o n dial ysis da ys s h o ul d be j u d ge d as a 
me dicati o n err or a n d re p orte d i n t he e C R F.  
A n o ver d ose wit h ass ociate d A Es is rec or de d as t he A E dia g n osis/ s y m pt o ms o n t he rele va nt 
A E m o d ules i n t he e C R F a n d o n t he O ver d ose e C R F m o d ule. 
A n o ver d ose wit h o ut ass ociate d s y m pt o ms is o nl y re p orte d o n t he O ver d ose e C R F m o d ule. 
If a n o ver d ose o n a n Astra Ze neca st u d y i nter ve nti o n occ urs i n t he c o urse of t he st u d y, t he 
i n vesti gat or or ot her site pers o n nel i nf or m a p pr o priate Astra Ze neca re prese ntati ves 
i m me diatel y, b ut n o l ater t h a n 2 4 h o urs  of w he n he or s he bec o mes a ware of it.  
T he desi g nate d Astra Ze neca re prese ntati ve w or ks wit h t he i n vesti gat or t o e ns ure t hat all 
rele va nt i nf or mati o n is pr o vi de d t o t he Astra Ze neca Patie nt Safet y data e ntr y site wit hi n 1 or 
5 c ale n d ar d a ys  f or o ver d oses ass ociate d wit h a n S A E (see Secti o n 8. 3. 6) a n d wit hi n 3 0 d a ys  
f or all ot her o ver d oses. 
8. 5  
H u m a n Bi ol o gic al S a m ples  
P har mac o ki netic  a n d p har mac o d y na mic para meters are n ot e val uate d i n t his st u d y, n or is 
i m m u n o ge nicit y. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 3  of 8 2  
8. 6  
H u m a n Bi ol o gic al S a m ple Bi o m ar kers  
Sa m ples f or bi o mar ker researc h are n ot re q uire d i n t his st u d y.  
8. 7  
O pti o n al Ge n o mics I niti ati ve S a m ple  
O pti o nal Ge n o mics I nitiati ve researc h is  n ot a p plica ble i n t his st u d y. 
9  
S T A TI S TI C A L C O N SI D E R A TI O N S  
9. 1  
St atistic al H y p ot heses  
T he pri mar y statistical h y p ot hesis of t he st u d y is t hat prescri bi n g S Z C wit h e n ha nce d 
n utriti o nal a d vice t o partici pa nts wit h h y per kalae mia o n hae m o dial ysis  will s h o w a 
n o n- i nferi or differe nce i n t he c ha n ge fr o m baseli ne i n S- K +  ta ke n at LI DI visits M 3, M 4, a n d 
M 5 w he n c o m pare d t o partici pa nt s o n S o C ( ot her t ha n K +  bi n ders). 
9. 2  
S a m ple Size Deter mi n ati o n  
Sa m ple size deter mi nati o n is base d u p o n t he pri mar y o bjecti ve of t he pri mar y esti ma n d, ie, To 
ev al u ate t he effect of t he c o m bi n ati o n of S Z C a n d e n h a nce d n utriti o n al a dvice t o c o ns u me 
fr uit a n d ve get a bles as c o m p are d t o S o C i n re d uci n g S- K + . 
Wit h 8 0 % p o wer t o reject t he pri mar y h y p ot hesis, 8 1 ra n d o mise d partici pa nts per treat me nt 
ar m ( 1 6 2 i n t otal) w o ul d be re q uire d usi n g a 2- gr o u p t- test wit h e q ual n’s wit h a 1-si de d al p ha 
of 0. 0 2 5, ass u mi n g a c o m m o n sta n dar d de viati o n acr oss treat me nt gr o u ps of 0. 4 5 a n d a 
n o n- i nferi orit y mar gi n of 0. 2 ( defi ne d as cli nicall y mea ni n gf ul b y scie ntific c o m mittee). It is 
e x pecte d t hat 1 5 % of partici pa nt s w h o e nter t he H K Treat me nt P hase will n ot c o nti n ue t o t he 
Diet C o m paris o n P hase, a n d c o nse q ue ntl y it is a ntici pate d t hat a p pr o xi matel y 1 9 1 partici pa nt s 
will e nter t he H K Treat me nt P hase  i n or der t o ac hie ve 1 6 2 ra n d o mise d. F urt her, t he scree ni n g 
fail ure rate is esti mate d t o be 5 0 %, mea ni n g 3 8 2 partici pa nt s will be e nr olle d. 
Partici pa nt s will be ra n d o mise d i nt o t he 4- m o nt h Diet C o m paris o n P hase  u ntil t he re q uire d 
n u m ber of ra n d o mis e d partici pa nt s is reac he d, at w hic h p oi nt t he recr uit me nt will st o p. 
9. 3  
P o p ul ati o ns f or A n al yses  
T he a nal ysis of data will be base d o n differe nt a nal ysis sets acc or di n g t o t he p ur p o se of 
a nal ysis, i.e. f or efficac y a n d safet y.  
Ta ble 6 
P o p ul ati o ns f or A n al ysis  
P o p ul ati o n  
Descri pti o n  
All -partici pa nts a nal ysis set 
T he all -partici pa nts a nal ysis set will c o nsist of all partici pa nt s w h o are 
scree ne d f or t he st u d y. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 4  of 8 2  
P o p ul ati o n  
Descri pti o n  
H K treat me nt safet y a nal ysis 
set ( H K S) 
T he H K S will i ncl u de all partici pa nt s w h o recei ve at least 1 d ose of S Z C 
d uri n g t he H K Treat me nt P hase . 
F ull a nal ysis set ( F A S)  
T he F A S, t he pri mar y efficac y a nal ysis set, will i ncl u de all ra n d o mi se d 
partici pa nt s, wit h partici pa nt s bei n g a nal yse d as ra n d o mise d, rat her t ha n as 
treate d. 
Safet y a nal ysis set ( S A S)  
T he S A S will i ncl u de all ra n d o mi se d partici pa nt s recei vi n g at least 1 d ose 
of st u d y treat me nt  d uri n g t he Diet C o m paris o n P hase , f or t he S Z C  ar m, a n d 
all ra n d o mise d partici pa nt s c o m pleti n g visit 5 f or t he So C ar m.  
A b bre viati o ns: H K = h y per kalae mia; S o C = sta n dar d of care; S Z C =  s o di u m zirc o ni u m c ycl osilicate.  
T he n u m ber of partici pa nt s i n eac h a nal ysis set, a n d t he n u m ber e xcl u de d a n d ass ociate d 
reas o ns will be s u m marise d b y treat me nt gr o u p a n d o verall. I n a d diti o n, t he f oll o wi n g peri o ds 
will be defi ne d f or t he p ur p ose of re p orti n g.  
Ta ble  7 
A n al ysis Peri o ds  
Peri o d  
Descri pti o n  
Scree ni n g  P hase  
Scree ni n g refers t o t he peri o d fr o m t he first st u d y s pecific assess me nt t o 
t he first d ose of S Z C d uri n g t he H K Treat me nt P hase or scree n fail ure , 
w hic he ver occ urs first  
H K Treat me nt P hase  
T he H K Treat me nt P hase ( o pe n -la bel peri o d) refers t o t he peri o d fr om t he 
date of first d ose of S Z C d uri n g t he H K Treat me nt P hase  u ntil t he date of 
ra n d o misati o n at t he start of t he Diet C o m paris o n P hase  
Diet C o m paris o n P hase  
T he Diet C o m paris o n P hase refers t o t he peri o d fr o m t he date of 
ra n d o misati o n u ntil t he earliest date of last assess me nt d uri n g t he f oll o w -u p 
peri o d, wit h dra wal of c o nse nt, last c o ntact wit h t he partici pa nt , or deat h 
A b bre viati o ns: H K = h y per kalae mia; S Z C = s o di u m zirc o ni u m c ycl osilicate.  
9. 4  
St atistic al A n al yses  
T he S A P will be drafte d a n d a p pr o ve d wit hi n 9 0 da ys of t he date of t he first partici pa nt 
e nr olle d, a n d a n y f urt her c ha n ges d uri n g t he c o urse of t he st u d y will be fi nalise d pri or t o Data 
Base L oc k . T he S A P will i ncl u de a m ore tec h nical a n d detaile d descri pti o n of t he stati stical 
a nal yses descri be d i n t his secti o n. T his secti o n is a s u m mar y of t he pla n ne d statistical a nal yses 
of t he m ost i m p orta nt e n d p oi nts i ncl u di n g pri mar y a n d ke y sec o n dar y e n d p oi nts. 
9. 4. 1  
Ge ner al C o nsi der ati o ns  
I nfere nce c o ncer ni n g t he pri mar y a nal ysis will be perf or me d at t he 1 -si de d 2. 5 % si g nifica nce 
le vel. All p oi nt esti mates will be prese nte d t o get her wit h c o nfi de nce i nter vals of 2-si de d 9 5 % 
c o vera ge, wit h g ui da nce i ncl u de d i n o ut p uts w here i nfere nce is base d u p o n 1 tail of t he 
i nter val. 
I nterc urre nt e ve nts are ha n dle d as o utli ne d wit hi n eac h secti o n f or t he pri mar y a n d sec o n dar y 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 5  of 8 2  
e n d p oi nts bel o w. F or t he pri mar y e n d p oi nt, missi n g data will occ ur i n t he case w here 
partici pa nt s are l ost t o f oll o w- u p, pr o vi de i ns ufficie nt e val ua ble data, wit hdra w c o nse nt , or die 
d uri n g t he st u d y. T he pr o p orti o n of partici pa nt s missi n g data f or t he pri mar y e n d p oi nt will be 
prese nte d al o n gsi de t he n u m ber of res p o nses a n d n o n- res p o nses. 
Baseli ne is defi ne d as t he last a vaila ble assess me nt pri or t o or o n t he date of t he ra n d o mis ati o n 
visit f or all partici pa nts, u nless ot her wise s pecifie d.  
I n ge neral ter ms, t he f ull a nal ysis set (F A S ) will be use d f or t he efficac y a nal yses, w hile t he 
H K safet y a nal ysis set ( H K S ) a n d safet y a nal ysis set (S A S ) will be use d f or t he safet y 
re p orti n g. 
I n ge neral, all baseli ne c haracteristics a n d efficac y a n d safet y varia bles will be s u m mari se d 
usi n g descri pti ve statistics as a p pr o priate. C o nti n u o us varia bles will be s u m mari se d b y 
descri pti ve statistics (i ncl u di n g n u m ber of partici pa nt s [ n], mea n, sta n dar d de viati o n, 
mi ni m u m, me dia n , a n d ma xi m u m). Cate g orical varia bles will be s u m mari se d usi n g 
fre q ue ncies a n d perce nta ges, w here t he de n o mi nat or of calc ulati o n is t he u n derl yi n g a nal ysis 
set p o p ulati o n u nless state d. 
D escri pti ve statistics of q ua ntitati ve efficac y a n d safet y para meters b y sc he d ule d visits will be 
pr o vi de d o n o bser ve d cases (ie, i ncl u di n g o nl y partici pa nt s w h o ha ve n o n-missi n g 
assess me nts at a gi ve n visit).  
9. 4. 2  
C O VI D -1 9 C o nsi der ati o ns  
It is a ntici pate d t hat a d diti o nal se nsiti vit y a n d s u p ple me ntar y a nal yses will be re q uire d t o 
deter mi ne t he i m pact of t he C O VI D - 1 9 pa n de mic o n t his trial a n d its e n d p oi nts. Pla n ne d 
se nsiti vit y a nal yses will disti n g uis h bet wee n pa n de mic a n d n o n- pa n de mic-relate d i nterc urre nt 
e ve nts i n ter ms of t he a p pr oac h ta ke n f or se nsiti vit y a nal yses. F urt her details will be i ncl u de d 
wit hi n t he S A P.  
9. 4. 3  
Effic ac y  
All efficac y e n d p oi nts will be a nal yse d usi n g t he F A S.  
9. 4. 3. 1  
Pri m ar y E n d p oi nt  
T he pri mar y e n d p oi nt will be defi ne d as t he c ha n ge i n t he ser u m K +  ta ke n at LI DI visits M 3, 
M 4 , a n d M 5 c o m pare d t o t he ser u m K + ta ke n at baseli ne.  
T he pri mar y o bjecti ve will test t he n ull h y p ot hesis of [ S- K +  f or S Z C  partici pa nts] – [ S- K +  f or 
S o C partici pa nt s] > = 0. 2 m m ol/ L a gai nst t he alter nati ve h y p ot hesis t hat [ S- K +  f or S Z C  
partici pa nt s] – [ S- K +  f or So C partici pa nt s] < 0. 2 m m ol/ L at t he 1-si de d 0. 0 2 5 si g nifica nce 
le vel. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 6  of 8 2  
T he pri mar y a nal ysis will acc o u nt f or missi n g val ues  a n d val ues rec or de d f or partici pa nt s after 
c o m me nce me nt of resc ue t hera p y of a K +  bi n der f or h y per kalae mia t hr o u g h a MI met h o d. A n y 
assess me nts perf or me d after t he i ntr o d ucti o n of resc ue t hera p y of a K + bi n der f or H K will n ot 
be use d as i n p uts f or t he MI  pr oce d ure. Precise details of t he MI pr ocess will be defi ne d 
wit hi n t he S A P.  
All sc he d ule d ass ess me nts d uri n g t he Diet C o m paris o n P hase  will be use d f or i m p utati o n a n d 
a nal ysis. I nter mitte nt o bser ve d val ues will be use d t o ge nerate a f ull set of i m p ute d val ues u p 
t o a n d i ncl u di n g M 5. 
A re peate d -meas ures  A N C O V A m o del will be use d f or eac h of t he c o m plete d datasets, wit h 
fi xe d ter ms f or t he treat me nt gr o u ps f or S Z C  a n d S oC, ti me p oi nt, baseli ne S- K +  as a c o variate, 
treat me nt b y ti me p oi nt as a n i nteracti o n. A d diti o nal m o del ter ms ma y be i ncl u de d, details of 
w hic h will be descri be d i n t he S A P. T he res ults fr o m eac h m o del will be rec o m bi ne d t o 
pr o vi de t he esti mate d c ha n ge fr o m baseli ne i n S- K +  f or eac h treat me nt gr o u p o ver t he peri o d 
of M 3 t o M 5, as well as t he bet wee n gr o u p differe nce a n d t he 9 5 % c o nfi de nce i nter val ( CI)  
f or t he bet wee n gr o u p differe nce. T he n ull h y p ot hesis will be rejecte d if t he u p per b o u n d of 
t he CI is bel o w 0. 2. 
9. 4. 3. 2  
Sec o n d ar y E n d p oi nts  
A m ulti plicit y c orrecti o n pr oce d ure t hat c o vers t he pri mar y a n d t he sec o n dar y e n d p oi nts will 
be a p plie d, wit h t he met h o d bei n g a fi xe d- se q ue nce hi erarc hical testi n g pr oce d ure w here  t he 
pri mar y h y p ot hesis is teste d first. If t he pri mar y e n d p oi nt or a n y of t he sec o n dar y e n d p oi nts 
liste d i n t he or der of i m p orta nce are ne gati ve, t he n all e n d p oi nts be neat h t he m i n t he hierarc h y 
are t he n re d uce d t o bei n g e x pl orat or y e n d p oi nts. T he or der of i m p orta nce f or t he sec o n dar y 
e n d p oi nts is as f oll o ws:  
•  Mai ntai ni n g S- K
+  le vels wit hi n a ra n ge of 3. 5 – 5. 5 m m ol/ L wit h o ut re q uiri n g resc ue 
t hera p y f or H K 
•  C o ns u m pti o n of fr uit a n d ve geta bles  
•  E Q - 5 D- 5 L sc ore 
•  K D Q O L - 3 6 P C S 
•  K D Q O L - 3 6 M C S 
•  T S Q M - 9 
•  P GI C . 
T he sec o n dar y e n d p oi nt of mai ntai ni n g S- K +  le vels wit hi n t he n or m o kalae mic ra n ge of 
3. 5- 5. 5 m m ol/ L wit h o ut re q uiri n g resc ue t hera p y f or H K will be assesse d as a bi nar y 
(res p o n der/ n o n-res p o n der) varia ble, wit h partici pa nt s bei n g dee me d res p o n ders if all of t he 
f oll o wi n g are tr ue: 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 7  of 8 2  
1.  T he partici pa nt  pr o vi des 2 or m ore n o n-missi n g S- K +  assess me nts d uri n g t he peri o d fr o m 
M 3 t o M 5, i ncl usi ve. 
2.  A t least 6 6 % of t heir n o n -missi n g S- K +  assess me nts bet wee n t he M 3 a n d M 5 visits , 
i ncl usi ve, s h o w val ues wit hi n t he n or m o kalae mic ra n ge. 
3.  T he partici pa nt  d oes n ot recei ve resc ue t hera p y or a K +  bi n der f or H K  at a n y p oi nt 
bet wee n t he M 3 a n d M 5 visits , i ncl usi ve. 
Partici pa nt s will be dee me d n o n-res p o n ders if p oi nt 3 is n ot tr ue, or if p oi nt 1 is tr ue  a n d p oi nt 
2 is n ot tr ue. 
Partici pa nts will be e xcl u de d fr o m t he sec o n dar y a nal ysis if p oi nt 1 is n ot tr ue a n d p oi nt 3 is 
tr ue. 
T his sec o n dar y o bjecti ve will test t he n ull h y p ot hesis of [ Pr o p orti o n of S Z C res p o n ders] – 
[ Pr o p orti o n of So C res p o n ders] < - 0. 1 a gai nst t he alter nati ve h y p ot hesis t hat [ Pr o p orti o n of 
S Z C res p o n ders] – [ Pr o p orti o n of So C res p o n ders] ≥ - 0. 1 at t he 1-si de d 0. 0 2 5 si g nifica nce 
le vel. 
T he pr o p orti o ns of res p o n ders a n d n o n- res p o n ders will be calc ulate d f or eac h treat me nt ar m, 
a n d a differe nce i n pr o p orti o ns ( S Z C - S o C) c o nstr ucte d. A 9 5 % 2- si de d CI  f or t he differe nce 
will be create d, a n d t he n ull h y p ot hesis will be rejecte d if t he l o wer b o u n d of t he CI is greater 
or e q ual t o - 0. 1. 
A se nsiti vit y a nal yses will be perf or me d w here partici pa nt s w h o disc o nti n ue d st u d y pri or t o 
pr o vi di n g a res p o nse f or t his sec o n dar y e n d p oi nt will be treate d as n o n-res p o n ders. Details 
re gar di n g se nsiti vit y a nal yses will be i ncl u de d i n t he S A P. 
C o ns u m pti o n of fr uit a n d ve geta bles will be trac ke d wit hi n t he N o o m a p p. Details  re gar di n g 
t he a nal ysis a n d prese ntati o n of data fr o m t his s o urce, i ncl u di n g h o w missi n g/i nc o m plete data 
is t o be ha n dle d, will be descri be d i n t he S A P.  
T he a vera ge dail y fr uit a n d ve geta ble c o ns u m pti o n per 2 8 da ys will be a nal yse d usi n g a 
re peate d-meas ures A N C O V A m o del wit h fi xe d ter ms f or treat me nt, 2 8 - da y peri o d, baseli ne 
a vera ge dail y c o ns u m pti o n, a n d treat me nt b y 2 8- da y peri o d i nteracti o n. T he c o m paris o n 
bet wee n treat me nt gr o u ps will be assesse d base d u p o n t he p -val ue ass ociate d wit h t he 
treat me nt b y 2 8- da y peri o d i nteracti o n ter m at M 5, w hic h will be prese nte d al o n gsi de t he L S  
mea n of t he M 5 treat me nt differe nce a n d its ass ociate d 9 5 % CI . F urt her, descri pti ve statistics, 
L S mea n esti mates, 9 5 % CIs , a n d p- val ues will be pr o vi de d per eac h 2 8- da y peri o d. 
T he E Q - 5 D- 5 L q uesti o n naire sc ore c ha n ge fr o m st u d y baseli ne at M 2 a n d M 5 will be 
a nal yse d usi n g a re peate d-meas ures A N C O V A m o del wit h fi xe d ter ms f or treat me nt, visit, 
baseli ne E Q - 5 D- 5 L, a n d treat me nt b y visit i nteracti o n. T he c o m paris o n bet wee n treat me nt 
gr o u ps will be assesse d base d u p o n t he p- val ue ass ociate d wit h t he treat me nt b y visit 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
4 8  of 8 2  
i nteracti o n ter m at t he M 5 visit, w hic h will be prese nte d al o n gsi de t he L S  mea n of t he o verall 
treat me nt differe nce a n d its ass ociate d 9 5 % CI . F urt her, descri pti ve statistics, L S mea n 
esti mates, 9 5 % CIs , a n d p- val ues will be pr o vi de d per visit. 
T he K D Q O L -3 6 sc ores f o r s y m pt o ms, P C S, a n d M C S will be a nal yse d a n d s u m marise d usi n g 
t he sa me A N C O V A a p pr oac h as f or t he E Q- 5 D-5 L.  
9. 4. 3. 3  
E x pl or at or y E n d p oi nts 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9. 4. 4  
S afet y  
Safet y will be assesse d i n ter ms of A Es, S A Es, A Es lea di n g t o treat me nt disc o nti n uati o n, 
cli nical la b orat or y data, vital si g ns , a n d E C G. A p pr o priate s u m maries of t hese data will be 
prese nte d b y treat me nt gr o u p. 
A Es will be classifie d usi n g t he Me dical Dicti o nar y f or Re g ulat or y Acti vities ( Me d D R A)  
s yste m or ga n class ( S O C) a n d preferre d ter m ( P T). A treat me nt-e mer ge nt A E ( T E A E) is 
defi ne d as a n A E wit h t he start date o n or after t he first d ose date a n d u p t o (a n d i ncl u di n g) 
1 4 da ys after t he last d ose date. O nl y T E A Es will be i ncl u de d i n ta ble s u m maries.  
T he n u m ber a n d perce nta ge of partici pa nts e x perie nci n g A Es, S A Es, A Es t hat le d t o 
wit h dra wal, A Es t hat le d t o deat h , a n d t he n u m ber of s uc h e ve nts, will be s u m marise d b y 
S O C, P T , a n d treat me nt gr o u p. T he n u m ber a n d perce nta ge of partici pa nts e x perie nci n g A Es 
will f urt her be s u m marise d b y i nte nsit y, a n d will be prese nte d wit h t he n u m ber of e ve nts at 
eac h le vel of i nte nsit y.  
A d diti o nall y, f or partici pa nt s i n t he S Z C  treat me nt ar m, t he n u m ber a n d perce nta ge of 
partici pa nt s wit h A Es lea di n g t o disc o nti n uati o n of S Z C  will be prese nte d b y S O C a n d P T, 
a n d t he n u m ber a n d perce nta ge of partici pa nt s wit h a n y A E will be prese nte d b y S O C, P T, 
a n d relati o ns hi p t o S Z C  as assesse d b y t he i n vesti gat or. Eac h of t hese S Z C  s u m maries will 
a d diti o nall y i ncl u de t he n u m ber of s uc h e ve nts.  
A n o ver vie w of I D W G a n d i nsta nces of S- K+  < 3. 5 will be prese nte d. 
C CI

Cli nical St u d y Pr ot oc ol  - 3. 0
Astra Ze neca
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4
C O N FI D E N TI A L A N D P R O P RI E T A R Y
4 9 of 8 2
All A E data will be liste d f or all partici pa nt s. I n a d diti o n, S A Es a n d A Es t hat le d t o 
wit h dra wal or deat h a n d treat me nt -relate d A Es will be liste d.
Cli nical safet y la b orat or y assess me nts will be s u m marise d a n d liste d. S hift ta bles will be
pr o vi de d f or select tests, w here s hift fr o m scree ni n g baseli ne t o t he w orst val ue wit hi n eac h 
part of t he st u d y a n d o verall will be s u m marise d. La b orat or y data o utsi de t he refere nce ra n ges 
will be i n dicate d i n all listi n gs.
All safet y a nal yses will be perf or me d o n t he Safet y Set. I n ge neral, safet y assess me nts will be 
re p orte d descri pti vel y b y treat me nt gr o u p. F ull details o n safet y a nal yses will be pr o vi de d i n 
t he S A P.
9. 5
I nteri m A n al yses
N ot a p plica ble. 
9. 6
D at a M o nit ori n g C o m mittee
N ot a p plica ble. 
1 0
S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S
Re g ul at or y, Et hic al, a n d St u d y O versi g ht 
C o nsi der ati o ns
A 1
Re g ul at or y a n d Et hic al C o nsi der ati o ns
•
T his st u d y will be c o n d ucte d i n acc or da nce wit h t he pr ot oc ol a n d wit h t he f oll o wi n g: 
−
C o nse ns us et hical pri nci ples deri ve d fr o m i nter nati o nal g ui deli nes i ncl u di n g t he 
Declarati o n of Helsi n ki a n d C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical 
Scie nces ( CI O M S) I nter nati o nal Et hical G ui deli nes
−
A p plica ble I C H G C P  G ui deli nes 
−
A p plica ble la ws a n d re g ulati o ns. 
•
T he pr ot oc ol, pr ot oc ol a me n d me nts, I C F, I B, a n d ot her rele va nt d oc u me nts ( e g,
a d vertise me nts) m ust be s u b mitte d t o a n I nstit uti o nal Re vie w B oar d ( I R B)/I n de pe n de nt 
Et hics C o m mittee ( IE C ) b y t he i n vesti gat or a n d re vie we d a n d a p pr o ve d b y t he I R B/I E C
bef ore t he st u d y is i niti ate d.
•
A n y a me n d me nts t o t he pr ot oc ol will re q uire I R B/I E C  a n d a p plica ble Re g ulat or y 
A ut h orit y a p pr o val bef ore i m ple me ntati o n of c ha n ges ma de t o t he st u d y desi g n, e xce pt 
f or c ha n ges necessar y t o eli mi nate a n i m me diate hazar d t o st u d y partici pa nts.

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 0  of 8 2  
•  
Astra Ze neca will be res p o nsi ble f or o btai ni n g t he re q uire d a ut h orisati o ns t o c o n d uct t he 
st u d y fr o m t he c o ncer ne d Re g ulat or y A ut h orit y. T his res p o nsi bilit y ma y be dele gate d t o a 
C o ntract Researc h Or ga ni sati o n, b ut t he acc o u nta bilit y re mai ns wit h Astra Ze neca.  
•  
T he i n vesti gat or will be res p o nsi ble f or pr o vi di n g o versi g ht of t he c o n d uct of t he st u d y at 
t he site a n d a d here nce t o re q uire me nts of 2 1 C o de of Fe deral Re g ulati o ns ( C F R ), I C H 
g ui deli nes, t he I R B/I E C, E ur o pea n Re g ulati o n 5 3 6/ 2 0 1 4 f or cli nical st u dies (i f 
a p plica ble), E ur o pea n Me dical De vice Re g ulati o n 2 0 1 7/ 7 4 5 f or cli nical de vice researc h 
(if a p plica ble), a n d all ot her a p plica ble l ocal re g ulati o ns. 
Re g ul at or y Re p orti n g Re q uire me nts f or S A Es  
•  
Pr o m pt n otificati o n b y t he i n vesti gat or t o t he s p o ns or of a n S A E  is esse ntial s o t hat le gal 
o bli gati o ns a n d et hical res p o nsi bilities t o war ds t he safet y of partici pa nts a n d t he safet y of 
a st u d y i nter ve nti o n u n der cli nical i n vesti gati o n are met.  
•  
T he s p o ns or has a le gal res p o nsi bilit y t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d 
ot her re g ulat or y a ge ncies a b o ut t he safet y of a st u d y i nter ve nti o n u n der cli nical 
i n vesti gati o n. T he s p o ns or will c o m pl y wit h c o u ntr y-s pecific re g ulat or y re q uire me nts 
relati n g t o safet y re p orti n g t o t he re g ulat or y a ut h orit y, I R B/I E C, a n d i n vesti gat ors. 
•  
F or all st u dies , e xce pt t h ose utilizi n g me dical de vices, i n vesti gat or safet y re p orts m ust be 
pre pare d f or s us pecte d u ne x pecte d seri o us a d verse reacti o ns ( S U S A R s) acc or di n g t o l ocal 
re g ulat or y re q uire me nts a n d s p o ns or p olic y a n d f or war de d t o i n vesti gat ors as necessar y. 
− 
E ur o pea n Me dical De vice Re g ulati o n 2 0 1 7/ 7 4 5 f or cli nical de vice researc h (if 
a p plica ble), a n d all ot her a p plica ble l ocal re g ulati o ns. 
•  
A n i n vesti gat or w h o recei ves a n i n vesti gat or safet y re p ort descri bi n g a n S A E or ot her 
s pecific safet y i nf or mati o n ( e g, s u m mar y or listi n g of S A Es) fr o m t he s p o ns or will re vie w 
a n d t he n file it al o n g wit h t he I B a n d will n otif y t he I R B/I E C, if a p pr o priate acc or di n g t o 
l ocal re q uire me nts. 
A 2  
Fi n a nci al Discl os ure  
I n vesti gat ors a n d s u b-i n vesti gat ors will pr o vi de t he s p o ns or wit h s ufficie nt, acc urate fi na ncial 
i nf or mati o n as re q ueste d t o all o w t he s p o ns or t o s u b mit c o m plete a n d acc urate fi na ncial 
certificati o n or discl os ure state me nts t o t he a p pr o priate re g ulat or y a ut h orities. I n vesti gat ors 
are res p o nsi ble f or pr o vi di n g i nf or mati o n o n fi na ncial i nterests d uri n g t he c o urse of t he st u d y 
a n d f or 1 year after c o m pleti o n of t he st u d y. 
A 3  
I nf or me d C o nse nt Pr ocess 
•  
T he i n vesti gat or or his/ her re prese ntati ve will e x plai n t he nat ure of t he st u d y t o t he 
partici pa nt or his/ her  le gall y a ut h orise d re prese ntati ve a n d a ns wer all q uesti o ns re gar di n g 
t he st u d y. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 1  of 8 2  
•  
Partici pa nts m ust be i nf or me d t hat t heir partici pati o n is v ol u ntar y a n d t he y are free t o 
ref use t o partici pate a n d ma y wit h dra w t heir c o nse nt at a n y ti me a n d f or a n y reas o n 
d u ri n g t he st u d y. Partici pa nts or t heir le gall y a ut h orise d re prese ntati ve will be re q uire d t o 
si g n a state me nt of i nf or me d c o nse nt t hat meets t he re q uire me nts of 2 1 C F R  5 0, l ocal 
re g ulati o ns, I C H g ui deli nes, Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act 
( HI P A A) re q uire me nts, w here a p plica ble, a n d t he I R B/I E C or st u d y site. 
•  
T he me dical rec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o nse nt was o btai ne d 
bef ore t he partici pa nt was e nr olle d i n t he st u d y a n d t he date t he writte n c o nse nt was 
o btai ne d. T he a ut h orise d pers o n o btai ni n g t he i nf or me d c o nse nt m ust als o si g n t he I C F. 
•  
T he first st u d y s pecific assess me nt has t o be perf or me d wit hi n 7 da ys after t he I C F has 
bee n si g ne d , all o wi n g t he scree ni n g p hase t o start at t he first st u d y s pecific assess me nt. 
•  
Partici pa nts m ust be re -c o nse nte d t o t he m ost c urre nt versi o n of t he I C F(s) d uri n g t heir 
partici pati o n i n t he st u d y.  
•  
A c o p y of t he I C F(s) m ust be pr o vi de d t o t he partici pa nt or t he partici pa nt’s le gall y 
a ut h orise d re prese ntati ve.  
A partici pa nt w h o is rescree ne d is n ot re q uire d t o si g n a n ot her I C F if t he rescree ni n g occ urs 
wit hi n 7 da ys fr o m t he pre vi o us I C F si g nat ure date.  
A 4  
D at a Pr otecti o n  
•  
Partici pa nts will be assi g ne d a u ni q ue i de ntifier b y t he s p o ns or. A n y partici pa nt rec or ds or 
datasets t hat are  tra nsferre d t o t he s p o ns or will c o ntai n t he i de ntifier o nl y; partici pa nt 
na mes or a n y i nf or mati o n t hat w o ul d ma ke t he partici pa nt i de ntifia ble will n ot be 
tra nsferre d. 
•  
T he partici pa nt m ust be i nf or me d t hat his/ her pers o nal st u d y -relate d data will be use d b y 
t he s p o ns or i n acc or da nce wit h l ocal data pr otecti o n la w. T he le vel of discl os ure a n d use 
of t heir data m ust als o be e x plai ne d t o t he partici pa nt i n t he i nf or me d c o nse nt. 
•  
T he partici pa nt m ust be i nf or me d t hat his/ her me dical rec or ds ma y be e xa mi ne d b y 
Cli nical Q ualit y Ass ura nce a u dit ors or ot her a ut h orise d pers o n nel a p p oi nte d b y t he 
s p o ns or, b y a p pr o priate I R B/I E C me m bers, a n d b y i ns pect ors fr o m re g ulat or y a ut h orities. 
A 5  
C o m mittees Str uct ure  
A Steeri n g C o m mittee c o nsisti n g of me m bers i n de pe n de nt of Astra Ze neca will be e n ga ge d 
d uri n g t he de vel o p me nt a n d c o n d uct of t his st u d y t o pr o vi de scie ntific a d vice o n t he st u d y 
desi g n a n d o bjecti ves. 
A 6  
Disse mi n ati o n of Cli nic al St u d y D at a  
A descri pti o n of t his cli nical st u d y will be a vaila ble o n 
htt p://astraze neca gr o u ptrials. p har mac m .c o m a n d htt p:// w w w.cli nicaltrials. g o v  as will t he 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 2  of 8 2  
s u m mar y of t he st u d y res ults w he n t he y are a vaila ble. T he cli nical st u d y a n d/ or s u m mar y of 
st u d y res ults ma y als o be a vaila ble o n ot her we bsites acc or di n g t o t he re g ulati o ns of t he 
c o u ntries i n w hic h t he st u d y is c o n d ucte d. 
A 7  
D at a Q u alit y Ass ur a nce  
•  
All partici pa nt data relati n g t o t he st u d y will be rec or de d i n t he e C R F u nless tra ns mitte d 
t o t he s p o ns or or desi g nee electr o nicall y (e g, la b orat or y data). T he i n vesti gat or is 
res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y electr o nicall y 
si g ni n g t he e C R F. 
•  
T he i n vesti gat or m ust mai ntai n acc urate d oc u me ntati o n (s o urce data) t hat s u p p orts t he 
i nf or mati o n e ntere d i n t he e C R F. 
•  
T he i n vest i gat or m ust per mit st u d y-relate d m o nit ori n g, a u dits, I R B/I E C re vie w, a n d 
re g ulat or y a ge nc y i ns pecti o ns a n d pr o vi de direct access t o s o urce data d oc u me nts. 
•  
M o nit ori n g details descri bi n g strate g y ( e g, ris k- base d i nitiati ves i n o perati o ns a n d q ualit y 
s uc h as Ris k Ma na ge me nt a n d Miti gati o n Strate gies a n d A nal ytical Ris k-Base d 
M o nit ori n g), met h o ds, res p o nsi bilities , a n d re q uire me nts, i ncl u di n g ha n dli n g of 
n o nc o m plia nce iss ues a n d m o nit ori n g tec h ni q ues (ce ntral, re m ote, or o n- site m o nit ori n g), 
are pr o vi de d i n t he M o nit ori n g Pla n. 
•  
T he s p o ns or or desi g nee is res p o nsi ble f or t he data ma na ge me nt of t his st u d y i ncl u di n g 
q ualit y c hec ki n g of t he data. 
•  
T he s p o ns or ass u mes acc o u nta bilit y f or acti o ns dele gate d t o ot her i n di vi d uals ( e g, 
C o ntract Researc h Or ga ni sati o ns). 
•  
St u d y m o nit ors will perf or m o n g oi n g s o urce data verificati o n t o c o nfir m t hat data e ntere d 
i nt o t he e C R F b y a ut h orise d site pers o n nel are acc urate, c o m plete, a n d verifia ble fr o m 
s o urce d oc u me nts; t hat t he safet y a n d ri g hts of partici pa nts are bei n g pr otecte d; an d t hat 
t he st u d y is bei n g c o n d ucte d i n acc or da nce wit h t he c urre ntl y a p pr o ve d pr ot oc ol a n d a n y 
ot her st u d y a gree me nts, I C H G C P, a n d all a p plica ble re g ulat or y re q uire me nts. 
•  
Rec or ds a n d d oc u me nts, i ncl u di n g si g ne d I C Fs, pertai ni n g t o t he c o n d uct of t his st u d y 
m ust be retai ne d b y t he i n vesti gat or f or 1 5 years after st u d y c o m pleti o n u nless l ocal 
re g ulati o ns or i nstit uti o nal p olicies re q uire a l o n ger rete nti o n peri o d. N o rec or ds ma y be 
destr o ye d d uri n g t he rete nti o n peri o d wit h o ut t he writte n a p pr o val of t he s p o ns or. N o 
rec or ds ma y be tra nsferre d t o a n ot her l ocati o n or part y wit h o ut writte n n otificati o n t o t he 
s p o ns or. 
A 8  
S o urce D oc u me nts  
•  
S o urce d oc u me nts pr o vi de e vi de nce f or t he e xiste nce of t he partici pa nt a n d s u bsta ntiate 
t he i nte grit y of t he data c ollecte d. So urce d oc u me nts are file d at t he i n vesti gat or’s site.  

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 3  of 8 2  
•  
Data e ntere d i n t he e C R F t hat are tra nscri be d fr o m s o urce d oc u me nts m ust be c o nsiste nt 
wit h t he s o urce d oc u me nts or t he discre pa ncies m ust be e x plai ne d. T he i n vesti gat or ma y 
nee d t o re q uest pre vi o us me d ical rec or ds or tra nsfer rec or ds, de pe n di n g o n t he st u d y. 
Als o, c urre nt me dical rec or ds m ust be a vaila ble.  
A 9  
St u d y a n d Site St art a n d Cl os ure  
T he st u d y start date is t he date o n w hic h t he cli nical st u d y will be o pe n f or recr uit me nt of 
partici pa nts.  
T he first  act of recr uit me nt i n t he first site acti vate d will  be t he st u d y start date.  
T he s p o ns or desi g nee reser ves t he ri g ht t o cl ose t he st u d y site or ter mi nate t he st u d y at a n y 
ti me f or a n y reas o n at t he s ole discreti o n of t he s p o ns or. St u d y sites will be cl osed u p o n st u d y 
c o m pleti o n. A st u d y site is c o nsi dere d cl ose d w he n all re q uire d d oc u me nts a n d st u d y s u p plies 
ha ve bee n c ollecte d a n d a st u d y site cl os ure visit has bee n perf or me d. 
T he i n vesti gat or ma y i nitiate st u d y  site cl os ure at a n y ti me, pr o vi de d t here is reas o na ble ca use 
a n d s ufficie nt n otice is gi ve n i n a d va nce of t he i nte n de d ter mi nati o n. 
Reas o ns f or t he earl y cl os ure of a st u d y site b y t he s p o ns or or i n vesti gat or ma y i ncl u de b ut are 
n ot li mite d t o: 
•  
Fail ure of t he i n vesti gat or t o c o m pl y wit h t he pr ot oc ol, t he re q uire me nts of t he I R B/I E C 
or l ocal healt h a ut h orities, t he s p o ns or's pr oce d ures, or G C P g ui deli nes 
•  
I na de q uate recr uit me nt of partici pa nts b y t he i n vesti gat or 
•  
Disc o nti n uati o n of f urt her st u d y i nter ve nti o n de vel o p me nt. 
If t he st u d y is pre mat urel y ter mi nate d or s us pe n de d, t he s p o ns or s hall pr o m ptl y i nf or m t he 
i n vesti gat ors, t he I E Cs/I R Bs, t he re g ulat or y a ut h orities, a n d a n y Co ntract R esearc h 
Or ga nisati o n(s) use d i n t he st u d y of t he reas o n f or ter mi nati o n or s us pe nsi o n, as s pecifie d b y 
t he a p plica ble re g ulat or y re q uire me nts. T he i n vesti gat or s hall pr o m ptl y i nf or m t he partici pa nt 
a n d s h o ul d ass ure a p pr o priate partici pa nt t hera p y a n d/ or f oll o w- u p. 
Partici pa nts  fr o m ter mi nate d sites will ha ve t he o p p ort u nit y t o be tra nsferre d t o a n ot her site t o 
c o nti n ue t he st u d y.  
A 1 0  
P u blic ati o n P olic y  
•  
T he res ults of t his st u d y ma y be p u blis he d or prese nte d at scie ntific meeti n gs. If t his is 
f oresee n, t he i n vesti gat or a grees t o s u b mit all ma n uscri pts or a bstracts t o t he s p o ns or 
bef ore s u b missi o n. T his all o ws t he s p o ns or t o pr otect pr o prietar y i nf or mati o n a n d t o 
pr o vi de c o m me nts. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 4  of 8 2  
•  
T he s p o ns or will c o m pl y wit h t he re q uire me nts f or p u blicati o n of st u d y res ults. I n 
acc or da nce wit h sta n dar d e dit orial a n d et hical practice, t he s p o ns or will ge nerall y s u p p o rt 
p u blicati o n of m ultice ntre st u dies o nl y i n t heir e ntiret y a n d n ot as i n di vi d ual site data. I n 
t his case, a c o or di nati n g i n vesti gat or will be desi g nate d b y m ut ual a gree me nt. 
•  
A ut h ors hi p will be deter mi ne d b y m ut ual a gree me nt a n d i n li ne wit h I nter nati o nal 
C o m mittee of Me dical J o ur nal E dit ors a ut h ors hi p re q uire me nts.  
 

Cli nical St u d y Pr ot oc ol  - 3. 0
Astra Ze neca
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4
C O N FI D E N TI A L A N D P R O P RI E T A R Y
5 5 of 8 2
A d verse E ve nts: Defi niti o ns a n d 
Pr oce d ures f or Rec or di n g, E v al u ati n g, 
F oll o w -u p, a n d Re p orti n g
B 1
Defi niti o n of A d verse E ve nts
A n a d verse e ve nt is t he de vel o p me nt of a n y u nt o war d me dical occ urre nce i n a pa tie nt or 
cli nical st u d y partici pa nt  a d mi nistere d a me dici nal pr o d uct a n d w hic h d oes n ot necessaril y 
ha ve a ca usal relati o ns hi p wit h t his treat me nt . A n A E ca n t heref ore be a n y u nfa v o ura ble a n d 
u ni nte n de d si g n ( e g, a n a b n or mal la b orat or y fi n di n g), s y m pt o m (f or e xa m ple , na usea, c hest 
pai n), or disease te m p orall y ass ociate d wit h t he use of a me dici nal pr o d uct, w het her or n ot 
c o nsi dere d relate d t o t he me dici nal pr o d uct. 
T he ter m A E is use d t o i ncl u de b ot h seri o us a n d n o n -seri o us A Es a n d ca n i ncl u de a 
deteri orati o n of a pre -e xisti n g me dical occ urre nce. A n A E ma y occ ur at a n y ti me, i ncl u di n g 
r u n-i n or was h o ut peri o ds, e ve n if n o st u d y i nter ve nti o n has bee n a d mi nistere d.
B 2
Defi niti o n of Seri o us A d verse E ve nts
A seri o us a d verse e ve nt is a n A E occ urri n g d uri n g a n y st u d y p hase (ie, r u n-i n, treat me nt, 
was h o ut, f oll o w- u p) t hat f ulfil s 1 or m ore of t he f oll o wi n g criteria:
•
Res ults i n deat h
•
Is i m me diatel y life-t hreate ni n g 
•
Re q uires i n -partici pa nt h os p italisati 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.
•
Res ults i n c o n ge nital a n o mal y or birt h defect
•
Is a n i m p orta nt me dical e ve nt t hat ma y je o par dise t he partici pa nt or ma y re q uire me dical 
treat me nt t o pre ve nt o ne of t he o utc o mes liste d a b o ve.
A d verse e ve nts ( A Es) f or m ali g n a nt t u m o urs  re p orte d d uri n g a st u d y s h o ul d ge nerall y be 
assesse d as Seri o us A Es . If n o ot her seri o us ness criteria a p pl y, t he ‘I m p orta nt Me dical E ve nt’ 
criteri o n s h o ul d be use d. I n certai n sit uati o ns, h o we ver, me dical j u d ge me nt o n a n i n di vi d ual 
e ve nt basis s h o ul d be a p plie d t o clarif y t hat t he mali g na nt t u m o ur e ve nt s h o ul d be assesse d 
a n d re p orte d as a n o n- seri o us A E . F or e xa m ple, if t he t u m o ur is i ncl u de d as me dical hist or y 
a n d pr o gressi o n occ urs d uri n g t he st u d y, b ut t he pr o gressi o n d oes n ot c ha n ge treat me nt a n d/ or 
pr o g n osis of t he mali g na nt t u m o ur, t he A E ma y n ot f ulfil t he attri b utes f or bei n g assesse d as 
seri o us, alt h o u g h re p orti n g of t he pr o gressi o n of t he mali g na nt t u m o ur as a n A E is vali d a n d 
s h o ul d occ ur. Als o, s o me t y pes of mali g na nt t u m o urs, w hic h d o n ot s prea d re m otel y after a 
r o uti ne treat me nt t hat d oes n ot re q uire h os pitalisati o n, ma y be assesse d as n o n-s eri o us; 
e xa m ples i n a d ults i ncl u de Sta ge 1 basal cell carci n o ma a n d Sta ge 1 A 1 cer vical ca ncer 
re m o ve d via c o ne bi o ps y. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 6  of 8 2  
Life -t hre ate ni n g 
‘ Life-t hreate ni n g’ mea ns t hat t he partici pa nt was at i m me diate ris k of deat h fr o m t he A E as it 
occ urre d or it is s us pect e d t hat use or c o nti n ue d use of t he pr o d uct w o ul d res ult i n t he 
partici pa nt’s deat h . ‘ Life-t hreate ni n g’ d oes n ot mea n t hat ha d a n A E occ urre d i n a m ore se vere 
f or m it mi g ht ha ve ca use d deat h (e g, he patitis t hat res ol ve d wit h o ut he patic fail ure).  
H os pit alis ati o n  
O ut patie nt treat me nt i n a n e mer ge nc y r o o m is n ot i n itself a seri o us AE, alt h o u g h t he reas o ns 
f or it ma y be (e g, br o nc h os pas m, lar y n geal oe de ma). H os pital a d missi o ns a n d/ or s ur gical 
o perati o ns pla n ne d bef ore or d uri n g a st u d y are n ot c o nsi dere d A Es i f t he ill ness or disease 
e xiste d bef ore t he partici pa nt  was e nr olle d i n t he st u d y, pr o vi de d t hat it di d n ot deteri orate i n 
a n u ne x pecte d wa y d uri n g t he st u d y. 
I m p ort a nt M e dic al E ve nt or M e dic al T re at me nt  
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 a case is seri o us i n 
sit uati o ns w here i m p orta nt me dical e ve nts ma y n ot be i m me diatel y life-t hreate ni n g or res ult i n 
deat h, h os pitalisati o n, disa bilit y , or i nca pacit y b ut ma y je o par d ise t he partici pa nt or ma y 
re q uire me dical treat me nt t o pre ve nt 1 or m ore o utc o mes liste d i n t he defi niti o n of seri o us. 
T hese s h o ul d us uall y be c o nsi dere d as seri o us.  
Si m pl y st o p pi n g t he s us pect dr u g d oes n ot mea n t hat it is a n i m p orta nt me dical e ve nt; me dical 
j u d ge me nt m ust be use d. 
•  
A n gi oe de ma n ot se vere e n o u g h t o re q uire i nt u bati o n b ut re q uiri n g i ntra ve n o us 
h y dr oc ortis o ne treat me nt 
•  
He pat ot o xicit y ca use d b y paraceta m ol (aceta mi n o p he n) o ver d ose re q uiri n g treat me nt wit h 
N- acet ylc ystei ne 
•  
I nte nsi ve treat me nt i n a n e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m 
•  
Bl o o d d yscrasias ( e g, ne utr o pe nia or a nae mia re q uiri n g bl o o d tra nsf usi o n) or c o n v ulsi o ns 
t hat d o n ot res ult i n h os pitalisati o n 
•  
De vel o p me nt of dr u g de pe n de nc y or dr u g a b use. 
I nte nsit y R ati n g S c ale: 
•  
Mil d (a ware ness of si g n or s y m pt o m, b ut easil y t olerate d)  
•  
M o derate ( disc o mf ort s ufficie nt t o ca use i nterfere nce wit h n or mal acti vities)  
•  
Se vere (i nca pacitati n g, wit h i na bilit y t o perf or m n or mal acti vities) . 
It is i m p orta nt t o disti n g uis h bet wee n seri o us a n d se vere A Es. Se verit y is a meas ure of 
i nte nsit y w hereas seri o us ness is defi ne d b y t he criteria i n A p pe n di x B 2. A n A E of se vere 
i nte nsit y nee d n ot necessaril y be c o nsi dere d seri o us. F or e xa m ple, na usea t hat persists f or 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 7  of 8 2  
se veral h o urs ma y be c o nsi dere d se vere na usea, b ut n ot an S A E u nless it meets t he criteria 
s h o w n i n A p pe n di x B 2.  O n t he ot her ha n d, a str o ke t hat res ults i n o nl y a li mite d de gree of 
disa bilit y ma y be c o nsi dere d a mil d str o ke b ut w o ul d be a n S A E w he n it satisfies t he criteria 
s h o w n i n A p pe n di x B 2.  
B 3  
A G ui de t o I nter preti n g t he C a us alit y Q uesti o n  
W he n ma ki n g a n assess me nt of ca usalit y , c o nsi der t he f oll o wi n g fact ors w he n deci di n g if 
t here is a ‘reas o na ble p ossi bilit y’ t hat a n A E ma y ha ve bee n ca use d b y t he dr u g. 
•  
Ti me C o urse. E x p os ure t o s us pect dr u g. Has t he partici pa nt act uall y recei ve d t he s us pect 
dr u g? Di d t he A E occ ur i n a reas o na bl e te m p oral relati o ns hi p t o t he a d mi nistrati o n of t he 
s us pect dr u g? 
•  
C o nsiste nc y wit h k n o w n dr u g pr ofile. Was t he A E c o nsiste nt wit h t he pre vi o us 
k n o wle d ge of t he s us pect dr u g ( p har mac ol o g y a n d t o xic ol o g y) or dr u gs of t he sa me 
p har mac ol o gical class? Or c o ul d  t he A E be a ntici pate d fr o m its p har mac ol o gical 
pr o perties? 
•  
De -c halle n ge  e x perie nce. Di d t he A E res ol ve or i m pr o ve o n st o p pi n g or re d uci n g t he d ose 
of t he s us pect dr u g? 
•  
N o alter nati ve ca use. T he A E ca n n ot be reas o na bl y e x plai ne d b y a n ot her aeti ol o g y s uc h 
as t he u n derl yi n g disease, ot her dr u gs, ot her h ost, or e n vir o n me ntal fact ors.  
•  
Re -c halle n ge  e x perie nce. Di d t he A E re occ ur if t he s us pecte d dr u g was rei ntr o d uce d after 
ha vi n g bee n st o p pe d? Astra Ze neca w o ul d n ot n or mall y rec o m me n d or s u p p ort a 
re-c halle n ge. 
•  
La b orat or y tests. A s pecific la b orat or y i n vesti gati o n (if perf or me d) has c o nfir me d t he 
relati o ns hi p. 
I n diffic ult cases, ot her fact ors c o ul d be c o nsi dere d s uc h as: 
•  
Is t his a rec o g nise d feat ure of o ver d ose of t he dr u g? 
•  
Is t here a k n o w n mec ha nis m? 
Ca usalit y of ‘relate d’ is ma de if , f oll o wi n g a re vie w of t he rele va nt data, t here is e vi de nce f or 
a ‘reas o na ble p ossi bilit y’ of a ca usal relati o ns hi p f or t he i n di vi d ual case. T he e x pressi o n 
‘reas o na ble p ossi bilit y’ of a ca usal relati o ns hi p is mea nt t o c o n ve y, i n ge neral, t hat t here are 
facts (e vi de nce) or ar g u me nts t o s u g gest a ca usal relati o ns hi p. 
T he ca usalit y assess me nt is perf or me d base d o n t he a vaila ble data i ncl u di n g e n o u g h 
i nf or mati o n t o ma ke a n i nf or me d j u d g me nt. Wit h n o a vaila ble facts or ar g u me nts t o s u g gest a 
ca usal relati o ns hi p, t he e ve nt(s) will be assesse d as ‘ n ot r elate d’. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 8  of 8 2  
Ca usal relati o ns hi p i n cases w here t he disease u n der st u d y has deteri orate d d ue t o lac k of 
effect s h o ul d be classifie d as n o reas o na ble p ossi bilit y. 
B 4  
Me dic ati o n Err or  
F or t he p ur p oses of t his cli nical st u d y a me dicati o n err or is a n u ni nte n de d fail ure or mista ke i n 
t he treat me nt pr ocess f or a n Astra Ze neca st u d y i nter ve nti o n t hat eit her ca uses har m t o t he 
partici pa nt or has t he p ote ntial t o ca use har m t o t he partici pa nt . 
A me dicati o n err or is n ot lac k of efficac y of t he dr u g, b ut rat her a h u ma n or pr o cess-relate d 
fail ure w hile t he dr u g is i n c o ntr ol of t he st u d y site staff or partici pa nt. 
Me dicati o n err or i ncl u des sit uati o ns w here a n err or : 
•  
Occ urre d  
•  
Was i de ntifie d a n d i nterce pte d bef ore t he partici pa nt recei ve d t he dr u g 
•  
Di d n ot occ ur, b ut circ u msta nces were rec o g nise d t hat c o ul d ha ve le d t o a n err or. 
E xa m ples of e ve nts t o be re p orte d i n cli nical st u dies as me dicati o n err ors:  
•  
Dr u g na me c o nf usi o n  
•  
Dis pe nsi n g err or , e g, me dicati o n pre pare d i nc orrectl y, e ve n if it was n ot act uall y gi ve n t o 
t he partici pa nt 
•  
Dr u g n ot a d mi nistere d as i n dicate d, e g, wr o n g r o ute or wr o n g site of a d mi nistrati o n  
•  
Dr u g n ot ta ke n as i n dicate d , e g, ta blet diss ol ve d i n water w he n it s h o ul d be ta ke n as a 
s oli d ta blet 
•  
Dr u g n ot st ore d as i nstr ucte d , e g, ke pt i n t he fri d ge w he n it s h o ul d be at r o o m te m perat ure  
•  
Wr o n g partici pa nt recei ve d t he me dicati o n (e xcl u di n g I R T/ R T S M err ors) 
•  
Wr o n g dr u g a d mi nistere d t o partici pa nt (e xcl u di n g I R T/ R T S M err ors) . 
E xa m ples of e ve nts t hat d o n ot  re q uire re p orti n g as me dicatio n err ors i n cli nical st u dies:  
•  
Err ors relate d t o or res ulti n g fr o m I R T/ R T S M - i ncl u di n g t h ose w hic h lea d t o 1 of t he 
a b o ve liste d e ve nts t hat w o ul d ot her wise ha ve bee n a me dicati o n err or  
•  
Partici pa nt acci de ntall y misse d dr u g d ose(s) , e g, f or g ot t o ta ke me dicati o n 
•  
Acci de ntal o ver d ose ( will be ca pt ure d as a n o ver d ose)  
•  
Partici pa nt faile d t o ret ur n u n use d me dicati o n or e m pt y pac ka gi n g 
•  
Err ors relate d t o bac k gr o u n d a n d resc ue me dicati o n, or S o C me dicati o n i n o pe n -la bel 
st u dies, e ve n if a n AstraZe neca pr o d uct . 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
5 9  of 8 2  
Me dicati o n err ors are n ot re gar de d as A Es , b ut A Es ma y occ ur as a c o nse q ue nce of t he 
me dicati o n err or.  
 

Cli nical St u d y Pr ot oc ol  - 3. 0
Astra Ze neca
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4
C O N FI D E N TI A L A N D P R O P RI E T A R Y
6 0 of 8 2
Electr o nic P atie nt -Re p orte d O utc o mes
C 1
K D Q O L ™- 3 6

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
6 1  of 8 2  
 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
6 2  of 8 2  
 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
6 3  of 8 2  
 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
6 4  of 8 2  
 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
6 5  of 8 2  
 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
6 6  of 8 2  
 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
6 7  of 8 2  
 
 
 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
6 8  of 8 2  
C 2  
E Q -5 D -5 L  
 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
6 9  of 8 2  
 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
7 0  of 8 2  
 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
7 1  of 8 2  
C 3  
T S M Q - 9 
T S Q M - 9 
A b bre vi ate d Tre at me nt S atisf acti o n Q uesti o n n aire f or Me dic ati o n  
 
I nstr ucti o ns: Please ta ke s o me ti me t o t hi n k a b o ut y o ur le vel of satisfacti o n or dissatisfacti o n 
wit h t he me dicati o n y o u are ta ki n g i n t his cli nical trial.  
We are i ntereste d i n y o ur e val uati o n of t he effecti ve nes s a n d c o n ve nie nce of t he me dicati o n 
over t he l ast t w o t o t hree weeks, or si nce y o u l ast use d it.   
F or eac h q uesti o n, please place a si n gle c hec k mar k ne xt t o t he res p o nse t hat m ost cl osel y 
c orres p o n ds t o y o ur o w n e x perie nces. 
1.  H o w s atisfie d or diss atisfie d are y o u wit h t he a bilit y of t he me dic ati o n t o pre ve nt 
or tre at y o ur c o n diti o n ? 
□1 E xtre mel y Dissatisfie d  
□2 Ver y Dissatisfie d  
□3 Dissatisfie d  
□4 S o me w hat Satisfie d  
□5 Satisfie d  
□6 Ver y Satisfie d  
□7 E xtre mel y Satisfie d  
 
2.  H o w s atisfie d or diss atisfie d ar e y o u wit h t he w a y t he me dic ati o n relie ves y o ur 
s y m pt o ms ? 
□1 E xtre mel y Dissatisfie d  
□2 Ver y Dissatisfie d  
□3 Dissatisfie d  
□4 S o me w hat Satisfie d  
□5 Satisfie d  
□6 Ver y Satisfie d  
□7 E xtre mel y Satisfie d  
 
 
 
 
C o p yri g ht © 2 0 0 7 Q ui ntiles. All Ri g hts Reser ve d  

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
7 2  of 8 2  
3.  H o w s atisfie d or diss atisfie d are y o u wit h t he a m o u nt of ti me it t a kes t he 
me dic ati o n t o st art w or ki n g ?  
□1 E xtre mel y Dissatisfie d  
□2 Ver y Dissatisfie d  
□3 Dissatisfie d  
□4 S o me w hat Satisfie d  
□5 Satisfie d  
□6 Ver y Satis fie d  
□7 E xtre mel y Satisfie d  
4.  H o w e as y or diffic ult is it t o use t he me dic ati o n i n its c urre nt f or m ?  
□1 E xtre mel y Diffic ult  
□2 Ver y Diffic ult  
□3 Diffic ult  
□4 S o me w hat Eas y  
□5 Eas y  
□6 Ver y Eas y  
□7 E xtre mel y Eas y  
5.  H o w e as y or diffic ult is it t o pl a n w he n y o u will use t he me dic ati o n e ac h ti me ?  
□1 E xtre mel y Diffic ult  
□2 Ver y Diffic ult  
□3 Diffic ult  
□4 S o me w hat Eas y  
□5 Eas y  
□6 Ver y Eas y  
□7 E xtre mel y Eas y  
6.  H o w c o n ve nie nt or i nc o n ve nie nt is it t o t a ke t he me dic ati o n as i nstr ucte d ?  
□1 E xtre mel y I nc o n ve nie nt  
□2 Ver y I nc o n ve nie nt 
□3 I nc o n ve nie nt 
□4 S o me w hat C o n ve nie nt 
□5 C o n ve nie nt 
□6 Ver y C o n ve nie nt 
□7 E xtre mel y C o n ve nie nt 
 
 
 
C o p yri g ht © 2 0 0 7 Q ui ntiles. All Ri g hts Reser ve d  

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
7 3  of 8 2  
7.  O ver all, h o w c o nfi de nt are y o u t h at t a ki n g t his me dic ati o n is a g o o d t hi n g f or 
y o u ? 
□1 N ot at All C o nfi de nt  
□2 A Little C o nfi de nt  
□3 S o me w hat C o nfi de nt 
□4 Ver y C o nfi de nt 
□5 E xtre mel y C o nfi de nt 
8.  H o w cert ai n are y o u t h at t he g o o d t hi n gs a b o ut y o ur me dic ati o n o ut wei g h t he b a d 
t hi n gs ? 
□1 N ot at All Certai n  
□2 A Little Certai n  
□3 S o me w hat Certai n  
□4 Ver y Certai n  
□5 E xtre mel y Certai n  
9.  Ta ki n g all t hi n gs i nt o acc o u nt, h o w s atisfie d or diss atisfie d are y o u wit h t his 
me dic ati o n ?  
□1 E xtre mel y Dissatisfie d  
□2 Ver y Dissatisfie d  
□3 Dissatisfie d  
□4 S o me w hat Satisfie d  
□5 Satisfie d  
□6 Ver y Satisfie d  
□7 E xtre mel y Satisfie d  
 
 
 
C o p yri g ht © 2 0 0 7 Q ui ntiles. All Ri g hts Reser ve d   
 
 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
7 4  of 8 2  
C 4  
P A TI E N T G L O B A L I M P R E S SI O N O F C H A N G E - P GI C  
 
O verall, h o w w o ul d y o u rate t he c ha n ge i n y o ur acti vit y li mitati o ns ( e g, co o ki n g a n d eati n g, 
d oi n g h o use h ol d c h ores or cli m bi n g stairs) si nce starti n g t his st u d y?  
Please select o ne res p o nse o nl y  
  
M uc h better  
  
A little better  
   
A b o ut t he sa me 
  
A little w orse  
   
M uc h w orse 
 
O verall, h o w w o ul d y o u rate t he c ha n ge i n y o ur Ki d ne y Disease s y m pt o ms (e g, lac k of a p petite 
or feeli n g tire d) si nce starti n g t his st u d y?  
Please select o ne res p o nse o nl y  
  
M uc h better  
  
A little better  
   
A b o ut t he sa me 
  
A little w orse  
   
M uc h w orse  
 
 
 
 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
7 5  of 8 2  
O verall, h o w w o ul d y o u rate t he c ha n ge i n y o ur e m oti o ns ( e g, feeli n g o ver w hel me d or 
de presse d) si nce starti n g t his st u d y?  
Please select o ne res p o nse o nl y  
  
M uc h better  
  
A little better  
   
A b o ut t he sa me 
  
A little w orse  
   
M uc h w orse  
 
O verall, h o w w o ul d y o u rate t he c ha n ge i n y o ur o verall q ualit y of life ( e g, satisfacti o n wit h 
life, or se nse of well bei n g) si nce starti n g t his st u d y? 
Please select o ne res p o nse o nl y  
  
M uc h better  
  
A little better  
   
A b o ut t he sa me 
  
A little w orse 
   
M uc h w orse 
 
 
  
 
 

Cli nical St u d y Pr ot oc ol  - 3. 0
Astra Ze neca
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4
C O N FI D E N TI A L A N D P R O P RI E T A R Y
7 6 of 8 2
M a n a ge me nt of St u d y Pr oce d ures D uri n g 
t he C O VI D-1 9 P a n de mic
D 1
I ntr o d ucti o n
Safe g uar di n g t he healt h a n d well bei n g of o ur partici pa nts a n d e ns uri n g t he c o nti n ue d s u p pl y 
of o ur me dici nes t o partici pa nts re mai ns of para m o u nt i m p orta nce f or Astra Ze neca t hr o u g h 
t he o n g oi n g C O VI D-1 9 o ut brea k.
N ote: C ha n ges bel o w s h o ul d be i m ple me nte d o nl y d uri n g st u d y disr u pti o ns d ue t o a n y of or a 
c o m bi nati o n of ci vil crisis, nat ural disaster, or p u blic healt h crisis ( e g, d uri n g q uara nti nes a n d 
res ulti n g site cl os ures, re gi o nal tra vel restricti o ns, a n d c o nsi derati o ns if site pers o n nel or st u d y 
partici pa nts bec o me i nfecte d wit h S A R S -C o V - 2 or si milar pa n de mic i nfecti o n) d uri n g w hic h 
partici pa nts ma y n ot wis h t o or ma y be u na ble t o visit t he st u d y site f or st u d y visits. T hese 
c ha n ges s h o ul d o nl y be i m ple me nte d if all o wa ble b y l ocal/re gi o nal g ui deli nes a n d f oll o wi n g 
a gree me nt fr o m t he s p o ns or. 
D 2
Ris k Assess me nt f or C O VI D -1 9 P a n de mic
S o di u m Zirc o ni u m C ycl osilicate ( S Z C) is a K +  bi n der acti n g i n t he gastr oi ntesti nal tract a n d is 
n ot a bs or be d. N o a d diti o nal r is k fr o m C O VI D- 1 9 is e x pecte d d ue t o S Z C. 
H o we ver, t he ris k of e x p os ure t o i nfecte d pe o ple ca n n ot be c o m pletel y e xcl u de d d uri n g st u d y 
partici pati o n as t he partici pa nts ma y nee d t o e x p ose t he msel ves t o p u blic areas (e g , c o m m ute 
t o t he site) a n d ha ve a d diti o nal h u ma n c o ntact (e g, wit h site staff).
D 2. 1
Me as ures t o Miti g ate t he Ris ks Ass oci ate d wit h C O VI D -1 9
•
T his st u d y will start or res u me e nr ol me nt o nl y w he n t he s p o ns or a n d i n vesti gat or dee m it 
a p pr o priate. I n a d diti o n, t he e nr ol me nt at a site le vel will o nl y star t or res u me w he n l ocal 
re g ulati o ns a n d g ui deli nes all o w. 
•
Nati o nal la ws a n d l ocal rec o m me n dati o ns re gar di n g t he pa n de mic will be strictl y a d here d 
t o. 
•
Site is e nc o ura ge d t o c o ntact t he partici pa nt wit hi n 1 da y pri or t o a st u d y visit t o as k f or 
si g ns a n d s y m pt o ms relate d t o C O VI D- 1 9. 
D 3
C O VI D -1 9 Pri or t o Scree ni n g
It is i m p orta nt t hat partici pa nts wit h p ossi ble o n g oi n g or n ot c o m pletel y res ol ve d C O VI D- 1 9 
i nfecti o n are n ot t o be e nr olle d i n t he st u d y. If t he partici pa nt has e vi de nce of C O VI D- 1 9 
wit hi n 2 wee ks pri o r t o scree ni n g (e g, a p ositi ve C O VI D -1 9 test or a cli nical ris k t hat has n ot 
bee n satisfact oril y e xcl u de d), t he partici pa nt ca n n ot be scree ne d a n d will be treate d acc or di n g 
t o S o C . 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
7 7  of 8 2  
D 4  
S us pecte d C O VI D -1 9 After Scree ni n g  
D 4. 1  
P artici p a nt is Se verel y Ill or H os pit ali se d 
If t he partici pa nt bec o mes s y m pt o matic after scree ni n g a n d has s us pecte d C O VI D- 1 9 
(re gar dless of a n y S A R S-C o V- 2 test res ults t hat ma y be a vaila ble), a n d is se verel y ill a n d/ or 
h os pitalis e d, t he partici pa nt ma y te m p oraril y or per ma ne ntl y disc o nti n ue st ud y i nter ve nti o n at 
t he discreti o n of t he site i n vesti gat or. 
D 4. 2  
P artici p a nt is N O T Se verel y Ill or H os pit ali se d 
If t he partici pa nt bec o mes s y m pt o matic after scree ni n g a n d has s us pecte d C O VI D- 1 9 
(re gar dless of w het her a n y S A R S-C o V- 2 test res ults are a vaila ble o r n ot), a n d is N O T se verel y 
ill a n d/ or h os pitalise d, t he i n vesti gat or s h o ul d deter mi ne if c o nti n uati o n of treat me nt wit h 
st u d y i nter ve nti o n is i n t he best i nterest of t he partici pa nt. 
Re gar dless if st u d y i nter ve nti o n is c o nti n ue d or n ot, t he partici pa nt is e nc o ura ge d t o atte n d t he 
st u d y visits acc or di n g t o sc he d ule. 
D 5  
C O VI D -1 9 D uri n g t he St u d y  
D 5. 1  
Rec o nse nt of St u d y P artici p a nts D uri n g St u d y I nterr u pti o ns  
D uri n g st u d y i nterr u pti o ns, it ma y n ot be p ossi ble f or t he partici pa nts t o c o m plete o n- site 
st u d y visits a n d assess me nts a n d alter nati ve mea ns f or carr yi n g o ut the visits a n d assess me nts 
ma y be necessar y, e g , re m ote visits. Rec o nse nt s h o ul d be o btai ne d f or t he alter nati ve mea ns of 
carr yi n g o ut visits a n d assess me nts a n d s h o ul d be o btai ne d pri or t o perf or mi n g t he pr oce d ures 
descri be d i n t he S o A ( Secti o n 1. 3). L ocal a n d re gi o nal re g ulati o ns a n d/ or g ui deli nes re gar di n g 
rec o nse nt of st u d y partici pa nts s h o ul d be c hec ke d a n d f oll o we d. 
Visiti n g t he st u d y sites f or t he s ole p ur p ose of o btai ni n g rec o nse nt s h o ul d be a v oi de d. 
D 5. 2  
Tele me dici ne Visit t o Re pl ace O n -site Visit ( W here A p plic a ble) 
I n t his a p pe n di x, t he ter m tele me dici ne visit refers t o re m ote c o ntact wit h t he st u d y 
partici pa nts usi n g telec o m m u nicati o ns tec h n ol o g y i ncl u di n g p h o ne calls, virt ual or vi de o 
visits, a n d m o bile healt h de vices. 
D uri n g a ci vil crisis, nat ural disaster, or p u blic healt h crisis, visits t hat are sc he d ule d t o be o n  
site ma y be re place d b y a tele me dici ne visit if all o we d b y l ocal/re gi o nal g ui deli nes. Ha vi n g a 
tele me dici ne c o ntact wit h t he partici pa nts will all o w A E s a n d c o nc o mita nt me dicati o n s t o be 
re p orte d a n d d oc u me nte d. 
D 5. 3  
D at a C a pt ure D uri n g Tele me dici ne Visits  
Data c ollecte d d uri n g tele me dici ne visits will be ca pt ure d b y t he q ualifie d H C P fr o m t he st u d y 
site. 

Cli nical St u d y Pr ot oc ol  - 3. 0
Astra Ze neca
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4
C O N FI D E N TI A L A N D P R O P RI E T A R Y
7 8 of 8 2
A b bre vi ati o ns
A b bre vi ati o n or s peci al 
ter m
E x pl a n ati o n
A E
ad verse eve nt
A N C O V A
a nal ysis of c o varia nce
C F R
C o de of Fe deral Re g ulati o ns
CI
c o nfi de nce i nter val
C K D
c hr o nic ki d ne y disease
C P S
calci u m p ol yst yre ne s ulf o nate
C S P
C li nical S t u d y P r ot oc ol
E C G
electr ocar di o gra m
e C R F
electr o nic Case Re p ort F or m
E D C 
electr o nic data ca pt ure
e P R O
electr o nic patie nt -re p orte d o utc o mes
E Q- 5 D - 5 L  
E ur o Q ol -5 Di me nsi o ns -5 Le vels
F A S
f ull a nal ysis set
G C P
G o o d Cli nical Practice
H C P
healt hcare pr o vi der
H K
h y per kalae mia
H R Q o L
healt h -relate d q ualit y of life
I B
I n vesti gat or’s Br oc h ure
I C F
Inf or me d C o nse nt F or m
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n
I D W G
i nter dial ytic wei g ht gai n
I E C 
I n de pe n de nt Et hics C o m mittee
I R B
I nstit uti o nal Re vie w B oar d
I R T
I nteracti ve Res p o nse Tec h n ol o g y
K +
p otassi u m
K D Q O L -3 6 
Ki d ne y Disease a n d Q ualit y of Life -3 6 ite m
LI DI
l o n g i nter dial ytic-dial ysis i nter val
L S 
least s q uares
M 
M o nt h
M C S
Me ntal C o m p o ne nt S u m mar y
MI
m ulti ple i m p utati o n
P C S
P h ysical C o m p o ne nt S u m mar y
P GI C
Patie nts’ Gl o bal I m pressi o n of C ha n ge

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
7 9  of 8 2  
A b bre vi ati o n or s peci al 
ter m 
E x pl a n ati o n  
P R O  
patie nt -re p orte d o utc o me 
P T  
preferre d ter m  
Q Tc 
Q T i nter val c orrecte d f or heart rate 
Q Tc F  
Q T i nter val c orrecte d f or heart rate usi n g Fri dericia’s met h o d  
R A A Si  
re ni n-a n gi ote nsi n -al d oster o ne s yste m i n hi bit or  
R T S M  
Ra n d o misati o n a n d Trial S u p pl y Ma na ge me nt  
S A E  
seri o us ad verse eve nt  
S A P  
S tatistical A nal ysis P la n 
S- K +  
ser u m p otassi u m 
S o A  
S c he d ule of A cti vities  
S o C 
sta n dar d of care 
S O C  
s yste m or ga n class 
S P S  
s o di u m p ol yst yre ne s ulf o nate 
S Z C 
s o di u m zirc o ni u m c ycl osilicate 
T E A E 
treat me nt-e mer ge nt a d verse e ve nt 
T S Q M -9  
A b bre viate d Treat me nt Satisfacti o n Q uesti o n naire f or Me dicati o n  (9 ite m s) 
U R R  
urea re d ucti o n rati o  
U S  
U nite d States  
V A S  
vis ual a nal o g ue scale  
W O C B P  
W o ma n of c hil d beari n g p ote ntial  
 
 
 

Cli nical St u d y Pr ot oc ol  - 3. 0
Astra Ze neca
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4
C O N FI D E N TI A L A N D P R O P RI E T A R Y
8 0 of 8 2
Pr ot oc ol A me n d me nt Hist or y
T he Pr ot oc ol A me n d me nt S u m mar y of C ha n ges Ta ble f or t he c urre nt a me n d me nt is l ocate d 
directl y bef ore t he Ta ble of C o nte nts.
A me n d me nt 1 0 5- M a y- 2 0 2 1 
T his a me n d me nt is c o nsi dere d t o be n o n -s u bsta ntial base d o n t he criteria set f ort h i n Article 
1 0(a) of Directi ve 2 0 0 1/ 2 0/ E C of t he E ur o pea n Parlia me nt a n d t he C o u ncil of t he E ur o pea n 
U ni o n beca use it neit her si g nifica ntl y i m pacts t he safet y or p h ysical/ me ntal i nte grit y of 
partici pa nts n or t he scie ntific val ue of t he st u d y.
O ver all R ati o n ale f or t he A me n d me nt:
Secti o n # a n d 
N a me
Descri pti o n of 
C h a n ge
Brief R ati o n ale
S u bst a nti al/ N o n -
s u bst a nti al 
Secti o n 1. 3 
Sc he d ule of 
Acti vities a n d 
Secti o n 6. 5 
C o nc o mita nt 
T hera p y
C ollecti o n of 
i nf or mati o n o n 
C O VI D -1 9 vacci nati o n 
has bee n clarifie d
T o s pecif y t hat C O VI D -1 9 
vacci nati o n at a n y ti me pri or t o 
e nr ol me nt s h o ul d be rec or de d 
i n t he e C R F
N o n -S u bsta ntial
A p pe n di x C 4 
Patie nt Gl o bal 
I m pressi o n of 
C ha n ge - P GI C
Pre vi o us versi o n of t he 
q uesti o n naire was 
re place d b y a ne w o ne
P GI C q uesti o n naire has bee n 
u p date d
N o n -s u bsta ntial
T hr o u g h o ut
Mi n or e dit orial a n d 
d oc u me nt f or matti n g 
re visi o ns
Mi n or, t heref ore ha ve n ot bee n 
s u m marise d 
N o n -s u bsta ntial

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o n i u m c ycl osilicate - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
8 1  of 8 2  
1 1  
R E F E R E N C E S  
At ki ns o n MJ, Si n ha A, Hass S L, C ol ma n S S, K u mar R N, Br o d M, et al. Vali dati o n of a 
ge neral meas ure of treat me nt satisfacti o n, t he Treat me nt Satisfacti o n Q uesti o n naire f or 
Me dicati o n ( T S Q M), usi n g a nati o nal pa nel st u d y of c hr o nic disease. He alt h Q u al Life 
O utc o mes . 2 0 0 4; 2( 1): 1 2. 
B har mal  M, Pa y ne K, At ki ns o n MJ. Vali dati o n of a n a b bre viate d Treat me nt Satisfacti o n 
Q uesti o n naire f or Me dicati o n  ( T S Q M- 9) a m o n g patie nts o n a nti h y perte nsi ve me dicati o ns. 
He alt h Q u al Life O utc o mes . 2 0 0 9; 7: 3 6 
C o he n D E, Lee A, Si b bel S, Be n ner D, Br u nelli S M, Te nt ori F. Use of t he K D Q O L- 3 6 T M  f or 
assess me nt of healt h -relate d q ualit y of life a m o n g dial ysis patie nts i n t he U nite d States. B M C 
Ne p hr ol . 2 0 1 9; 2 0( 1): 1 1 2. 
El - S har ka w y M, K he dr E, A b del w ha b S, Ali M, El Sai d K. Pre vale nce of h y per kalae mia 
a m o n g hae m o dial ysis patie nts i n E g y pt. Re n F ail . 2 0 0 9; 3 1( 1 0): 8 9 1 – 8. 
G ora ya N, M u n oz- Mal d o na d o Y, Si m o ni J, Wess o n D E. Fr uit a n d ve geta ble treat me nt of 
c hr o nic ki d ne y disease- relate d meta b olic aci d osis re d uces car di o vasc ular ris k better t han 
s o di u m bicar b o nate. A m J Ne p hr ol . 2 0 1 9; 4 9( 6): 4 3 8 – 4 8. 
G ora ya N, Si m o ni J, J o C- H, Wess o n D E. Treat me nt of meta b olic aci d osis i n patie nts wit h 
sta ge 3 c hr o nic ki d ne y disease wit h fr uits a n d ve geta bles or oral bicar b o nate re d uces uri ne 
a n gi ote nsi n o ge n a n d p reser ves gl o mer ular filtrati o n rate. Ki d ney I nt . 2 0 1 4; 8 6( 5): 1 0 3 1 – 8. 
Ha yes C P, Mc Le o d M E, R o bi ns o n R R. A n e xtra ve nal mec ha nis m f or t he mai nte na nce of 
p otassi u m bala nce i n se vere c hr o nic re nal fail ure. Tr a ns Ass oc A m P hysici a ns . 1 9 6 7; 8 0: 2 0 7 –
1 6. 
Her d ma n M, G u de x C, Ll o y d A, Ja nsse n M F, Ki n d P, Par ki n D, et al. De vel o p me nt a n d 
preli mi nar y testi n g of t he ne w fi ve -le vel versi o n of E Q-5 D ( E Q - 5 D- 5 L). Q u al Life Res . 
2 0 1 1; 2 0( 1 0): 1 7 2 7 – 3 6. 
Ki m H, Ca ulfiel d L E, Garcia -Larse n V, Steffe n L M, Gra ms M E, C ores h J, et al. Pla nt -base d 
diets a n d i nci de nt C K D  a n d ki d ne y f u ncti o n. Cli n J A m S oc Ne p hr ol . 2 0 1 9; 1 4( 5): 6 8 2 –9 1.  
Li u Y, K ucz mars ki M F, Miller E R, Na va M B, Z o n der ma n A B, E va ns M K, et al. Dietar y 
ha bits a n d ris k of ki d ne y f u ncti o n decli ne i n a n ur ba n p o p ulati o n. J Re n N utr . 2 0 1 7; 2 7( 1): 1 6–
2 5. 

Cli nical St u d y Pr ot oc ol  - 3. 0  
Astra Ze neca  
S o di u m zirc o ni u m c ycl osilicate  - D 9 4 8 0 C 0 0 0 1 4  
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
8 2  of 8 2  
Ricar d o A, Hac ker H, L ora C, Ac kers o n L, De Sal v o K, G o A et al. Vali dati o n of t he Ki d ne y 
Disease Q ualit y of Life S h ort F or m 3 6 ( K D Q O L - 3 6) U S S pa nis h a n d E n glis h versi o ns i n a 
c o h ort of His pa nics wit h c hr o nic ki d ne y disease. Et h n Dis . 2 0 1 3; 2 3( 2): 2 0 2- 9. 
Sie ner R. Dietar y treat me nt of meta b olic aci d osis i n c hr o nic ki d ne y disease. N utrie nts . 
2 0 1 8; 1 0( 4): 5 1 2. 
S o di u m Zirc o ni u m C ycl osilicate ( L o kel maT M ) I n vesti gat or Br oc h ure E diti o n 9, date d 1 st 
N o ve m ber 2 0 1 9. 
Wai S N, Kell y J T, J o h ns o n D W, Ca m p bell K L. Dietar y patter ns a n d cli nical o utc o mes i n 
c hr o nic ki d ne y disease: t he C K D. Q L D N utriti o n St u d y. J Re n N utr . 2 0 1 7; 2 7( 3): 1 7 5 –8 2.  

SI G N A T U R E P A G E
T his is a re prese nt ati o n of a n electr o nic rec or d t h at w as si g ne d
electr o nic ally a n d t his p a ge is t he m a nifest ati o n of t he electr o nic si g n at ure
D oc u me nt N a me: d 9 4 8 0c 0 0 0 1 4-cs p- v 3
D oc u me nt Title:
D 9 4 8 0 C 0 0 0 1 4 Cli nical St u d y Pr ot oc ol versi o n 3
D oc u me nt I D:
D oc I D- 0 0 4 5 1 8 6 0 4
Versi o n L a bel:
3. 0 C U R R E N T L A T E S T A P P R O V E D
Ser ver D ate
( d d- M M M- y y y y H H: m m ‘ U T C’ Z)
Si g ne d b y
Me a ni n g of Si g n at ure
C o nte nt A p pr o val
C o nte nt A p pr o val
N otes: ( 1) D oc u me nt details as st ore d i n A N G E L, a n Astra Ze neca d oc u me nt ma na ge me nt s yste m.
P P D
P P D