Clinical trial NCT04549597
Conditions: Chronic Kidney Disease Requiring Chronic Dialysis Hyperphosphatemia
Keywords: hyperphosphatemia
Sponsor: Ardelyx
Start date: 2020-11-20; Completion date: 2021-12-01
Enrollment: 333 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized, open-label study to evaluate different methods of initiating tenapanor therapy in CKD patients on dialysis with hyperphosphatemia, when they are either phosphate binder naïve or on phosphate binder therapy. The objective to evaluate the effect of tenapanor alone or in combination with phosphate binders to achieve target serum phosphorus (s-P) levels of ≤5.5 mg/dL when tenapanor is administered as the core therapy (alone or in combination with phosphate binders) for the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis.

Detailed description:
Approximately 330 CKD patients on dialysis with hyperphosphatemia (\>4.5 mg/dL) will be enrolled in this study.

This is a randomized, open-label study to evaluate different methods of initiating tenapanor therapy in CKD patients on dialysis with hyperphosphatemia, when they are either phosphate binder naïve or on phosphate binder therapy.

The study consists of a Screening visit and a 10-week open-label Treatment Period (TP), for which

* Patients with s-P \>5.5 and ≤10.0 mg/dL under stable phosphate binder treatment are randomized in a 1:1 ratio to two different treatment cohorts:

  * Cohort 1 (straight switch), which stops taking phosphate binders and is started on tenapanor 30 mg twice daily (BID) at Visit 2 (Day 1);
  * Cohort 2, which decreases phosphate binder dose by at least 50% (may be more than 50% if patient is taking an odd number of binder pills each day), with ability to switch the binder regimen from thrice daily (TID) to BID or QD; and initiates tenapanor 30 mg BID at Visit 2 (Day 1).
* Phosphate binder naïve patients with s-P \>4.5 and ≤10.0 mg/dL are enrolled as Cohort 3 and receive tenapanor at Visit 2 (Day 1) with a starting dose of 30 mg BID.
* Patients on phosphate binder therapy must receive phosphate binder(s) thrice daily, and both the s-P level assessed at the most recent measurement prior to the Screening visit (Visit 1) and the s-P level assessed at the Screening visit (Visit 1) must be \>5.5 and ≤10.0 mg/dL to qualify for randomization into Cohort 1 or Cohort 2 at Visit 2 (Day 1).
* Phosphate binder naïve patients must have the s-P level assessed at the Screening visit (Visit 1) \>4.5 and ≤10.0 mg/dL to qualify for enrollment into Cohort 3 at Visit 2 (Day 1).

Patients who do not meet the randomization/enrollment criteria on s-P will be discontinued as screen failures.

During the TP, patients will receive tenapanor starting at a dose of 30 mg twice daily. Tenapanor will be taken twice daily; just prior to breakfast and dinner. The Investigator may titrate the dose of tenapanor in 10 mg increments down to a minimum of 10 mg QD or up to a maximum of 30 mg BID at any time during the study based on s-P levels and/or gastrointestinal (GI) tolerability.

Arms: arm 1: Patients stop taking phosphate binders and start tenapanor 30 mg twice daily arm 2: Decreases phosphate binder dose by at least 50% with the ability to switch the binder regiment from thrice daily (TID) to BID or once a day and initiates tenapanor 30 mg BID arm 3: Phosphate binder naive patients are enrolled as Cohort 3 and receive tenapanor with a starting dose of 30 mg/BID
Interventions: intervention 1: Tenapanor
Intervention descriptions: intervention 1: Use of tenapanor

Protocol documents:
Prot_SAP_000.pdf: 
C LI NI C A L T RI A L P R O T O C O L 
St u d y T E N- 0 2- 4 0 2 ( O P TI MI Z E) 
A Ra n d o mize d, O pe n- La bel St u d y t o E val uate t h e Use of Te na pa n or as t he C ore T hera p y i n 
t he Treat me nt of H y per p h os p hate mia i n Patie nts wit h C hr o nic Ki d ne y Disease o n Dial ysis 
w h o are P h os p hate Bi n der Naï ve or o n P h os p ha te Bi n der T hera p y, t o O pti mize P h os p h or us 
Ma na ge me nt ( O P TI MI Z E) 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 1 
3 1 J ul y  2 0 2 0 
E diti o n N o. 2 
2 3 Fe br uar y  2 0 2 1  
S p o ns or: 
Ar del y x, I nc. 
3 4 1 7 5 Ar de n w o o d Bl v d. 
Fre m o nt, C A 9 4 5 5 5 
P h o ne: ( 5 1 0) 7 4 5- 1 7 5 2 
Fa x: ( 5 1 0) 7 4 5- 0 3 9 9 
C o nfi de nti alit y St ate me nt 
T his d oc u me nt a n d t he i nf or mati o n c o ntai ne d herei n or attac he d heret o (" C o nfi de ntial Material") are 
c o nfi de ntial a n d pr o prietar y t o Ar del y x, I nc.. T his C o nfi de ntial Material s h o ul d be vie we d o nl y b y t h ose 
i n di vi d uals or c o m pa nies t hat ha ve bee n gi ve n pri or a ut h orizati o n t o d o s o b y Ar del y x, I nc. (" A ut h orize d 
Users"). T his C o nfi de ntial Material s h o ul d n ot be ma de a vaila ble i n a n y f or m t o a n y pers o n or c o m pa n y, ot her 
t ha n t he A ut h orize d Users a n d t heir res pecti ve e m pl o yees or ass ociates o n a nee d-t o- k n o w basis, wit h o ut t he 
pri or writte n c o nse nt fr o m Ar del y x, I nc.  


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L 
Pa ge 2 
T A B L E O F C O N T E N T S 
T A B L E O F C O N T E N T S ............................................................................................... 2  
1  
G E N E R A L I N F O R M A TI O N ....................................................................... 5  
1. 1  
St u d y A d mi nistr ati ve Str uct ure ............................................................ 5  
1. 2  
S y n o psis ................................................................................................... 6  
1. 3  
Sc he d ule of Assess me nts a n d Pr oce d ures ........................................... 1 5  
1. 4  
List of A b bre vi ati o ns ............................................................................ 1 8  
2  
I N T R O D U C TI O N A N D B A C K G R O U N D ................................................ 2 0 
2. 1  
I ntr o d ucti o n ........................................................................................... 2 0 
2. 2  
Descri pti o n of I n vesti g ati o n al Pr o d uct ............................................... 2 1  
2. 3  
St u d y R ati o n ale ..................................................................................... 2 2  
2. 4  
Ris k- Be nefit Assess me nt....................................................................... 2 2  
3  
S T U D Y O B J E C TI V E S ................................................................................ 2 3  
3. 1  
Pri m ar y O bjecti ve ................................................................................. 2 3  
3. 2  
Sec o n d ar y O bjecti ves ........................................................................... 2 4  
4  
S T U D Y D E SI G N .......................................................................................... 2 4  
4. 1  
Desi g n S u m m ar y ................................................................................... 2 4  
4. 1. 1  
D urati o n of St u d y ................................................................................... 2 7  
5  
S E L E C TI O N A N D WI T H D R A W A L O F P A TI E N T S ............................ 2 7  
5. 1  
I ncl usi o n Criteri a .................................................................................. 2 7 
5. 2  
E xcl usi o n Criteri a ................................................................................. 2 8  
5. 3  
P atie nt Wit h dr a w al............................................................................... 2 9  
5. 4  
E arl y Ter mi n ati o n of St u d y ................................................................. 2 9  
6  
T R E A T M E N T O F P A TI E N T S .................................................................. 2 9  
6. 1  
A d mi nistr ati o n of I n vesti g ati o n al Pr o d uct ......................................... 2 9  
6. 1. 1  
I de ntit y of I n vesti gati o nal Pr o d uct(s) ..................................................... 2 9 
6. 1. 2  
I de ntit y of P h os p hate Bi n ders ................................................................. 3 0 
6. 1. 3  
Treat me nts A d mi nistere d ........................................................................ 3 0  
6. 1. 4  
D ose A dj ust me nts ................................................................................... 3 0  
6. 1. 5  
Met h o d of Assi g ni n g Patie nts t o Treat me nt Gr o u ps .............................. 3 2 
6. 2  
I n vesti g ati o n al Pr o d uct St or a ge a n d Acc o u nt a bilit y ......................... 3 3  
6. 2. 1  
St ora ge C o n diti o ns .................................................................................. 3 3  
6. 2. 2  
Dr u g Acc o u nta bilit y ............................................................................... 3 3  
6. 3  
P ac k a gi n g a n d L a beli n g ....................................................................... 3 4  
6. 3. 1  
St u d y Dr u g .............................................................................................. 3 4  
6. 3. 2  
Bli n di n g Met h o ds ................................................................................... 3 4  
6. 4  
Pri or a n d C o nc o mit a nt T her a p y ......................................................... 3 4  
7  
C O L L E C TI O N O F S T U D Y V A RI A B L E S ............................................... 3 5  
7. 1  
Rec or di n g of D at a ................................................................................. 3 5  


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L 
Pa ge 3 
7. 2  
D at a C ollecti o n Pri or t o E nr oll me nt ................................................... 3 5  
7. 3  
T oler a bilit y a n d S afet y Me as ures ........................................................ 3 6  
7. 3. 1  
St o ol Fre q ue nc y a n d C o nsiste nc y ........................................................... 3 6  
7. 3. 2  
P h ysical E xa mi nati o n ............................................................................. 3 7  
7. 3. 3  
B o d y Wei g ht a n d Vital Si g ns ( bl o o d press ure a n d heart rate) ............... 3 8  
7. 3. 4  
Electr ocar di o gra m ................................................................................... 3 8  
7. 3. 5  
Cli nical La b orat or y Tests........................................................................ 3 8  
7. 4  
A d verse E ve nts ...................................................................................... 3 9  
7. 4. 1  
Rec or di n g A d verse E ve nts...................................................................... 4 0  
7. 4. 2  
Assess me nt of A d verse E ve nts ............................................................... 4 1  
7. 4. 3  
F oll o wi n g A d verse E ve nts ...................................................................... 4 1  
7. 4. 4  
Disc o nti n uati o n d ue t o A d verse E ve nt ................................................... 4 1  
7. 4. 5  
Pre g na nc y................................................................................................ 4 1  
7. 4. 6  
Seri o us A d verse E ve nts .......................................................................... 4 2  
7. 4. 7  
Re p orti n g Seri o us A d verse E ve nts ......................................................... 4 3  
7. 5  
Effic ac y E n d p oi nts ................................................................................ 4 3  
8  
M E T H O D O L O G Y/ S T U D Y VI SI T S .......................................................... 4 5  
8. 1  
P atie nt E d uc ati o n .................................................................................. 4 5  
8. 2  
P atie nt E x perie nce Assess me nt ........................................................... 4 6  
8. 3  
Scree ni n g Pr oce d ures: Visit 1 ( D a y - 2) ............................................... 4 6  
8. 4  
Tre at me nt Peri o d: Visit 2 ( D a y 1) ....................................................... 4 7  
8. 5  
Tre at me nt Peri o d: Visits 3, 4, 5, 6, 7 a n d 8 ( D a ys 8, 1 5, 2 2, 2 9, 
4 3, a n d 5 7 ± 2 D a ys) .............................................................................. 4 7  
8. 6  
E n d of Tre at me nt Peri o d or St ar t of E xte nsi o n Peri o d: Visit 9 
( D a y 7 1 ± 2 D a ys) .................................................................................. 4 8 
8. 7  
O pti o n al E xte nsi o n Peri o d: Visits 1 0, 1 1, a n d 1 2 ( D a ys 1 0 1, 1 3 1, 
a n d 1 6 1 ± 7 D a ys) .................................................................................. 4 8  
8. 8  
E n d of E xte nsi o n Peri o d: Visit 1 3 ( D a y 1 9 1 ± 7 D a ys) ...................... 4 8  
8. 9  
E arl y Ter mi n ati o n Visit ....................................................................... 4 9  
8. 1 0  
Wit h dr a w al Pr oce d ures ....................................................................... 4 9  
8. 1 1  
Criteri a f or St u d y Ter mi n ati o n ........................................................... 4 9  
8. 1 2  
T ot al Bl o o d V ol u me Re q uire d f or St u d y ............................................ 5 0  
8. 1 3  
Pr ot oc ol De vi ati o ns ............................................................................... 5 0  
9  
S T A TI S TI C A L C O N SI D E R A TI O N S ....................................................... 5 1  
9. 1  
St atistic al A n al ysis Pl a n ....................................................................... 5 1  
9. 2  
Deter mi n ati o n of S a m ple Size .............................................................. 5 1  
9. 3  
A n al ysis P o p ul ati o ns ............................................................................. 5 1  
9. 4  
St atistic al Met h o ds ................................................................................ 5 2  
9. 4. 1  
Ge neral C o nsi derati o ns ........................................................................... 5 2  
9. 4. 2  
Baseli ne Descri pti ve Statistics ................................................................ 5 2  
9. 4. 3  
Efficac y A nal ysis .................................................................................... 5 2  
9. 4. 4  
Ha n dli n g of Missi n g Data ....................................................................... 5 2  
9. 4. 5  
A dj ust me nts f or C o variates .................................................................... 5 3  
9. 4. 6  
Visit Wi n d o ws ........................................................................................ 5 3  


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L 
Pa ge 4 
9. 4. 7  
Safet y a n d T olera bilit y A nal yses ............................................................ 5 3  
9. 4. 8  
I nteri m A nal ysis ...................................................................................... 5 3 
1 0  
A C C E S S T O S O U R C E D A T A/ D O C U M E N T S ........................................ 5 4  
1 1  
Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E ......................... 5 4  
1 1. 1  
C o n d uct of St u d y .................................................................................. 5 4  
1 1. 2  
Pr ot oc ol A me n d me nts .......................................................................... 5 5  
1 1. 3  
M o nit ori n g of St u d y ............................................................................. 5 5  
1 2  
E T HI C S ........................................................................................................ 5 5  
1 2. 1  
I nstit uti o n al Re vie w B o ar d/I n de pe n de nt Et hics C o m mittee 
A p pr o v al ................................................................................................ 5 5  
1 2. 1. 1  
Et hics Re vie w Pri or t o St u d y .................................................................. 5 5  
1 2. 1. 2  
Et hics Re vie w of ot her D oc u me nts ........................................................ 5 6  
1 2. 2  
Writte n I nf or me d C o nse nt ................................................................... 5 6  
1 3  
D A T A H A N D LI N G A N D R E C O R D K E E PI N G ...................................... 5 6  
1 3. 1  
D at a Re p orti n g a n d Electr o nic D at a C a pt ure ................................... 5 6  
1 3. 1. 1  
Electr o nic Case Re p ort F or ms (e C R Fs) .................................................. 5 6  
1 3. 1. 2  
La b orat or y Data ...................................................................................... 5 6  
1 3. 1. 3  
Rete nti o n of S o urce D oc u me nts ............................................................. 5 6  
1 3. 2  
Rete nti o n of Esse nti al D oc u me nts ....................................................... 5 7  
1 4  
A D MI NI S T R A TI V E I N F O R M A TI O N ..................................................... 5 7  
1 4. 1  
Fi n a nci n g a n d I ns ur a nce ...................................................................... 5 7  
1 4. 2  
P u blic ati o n P olic y ................................................................................. 5 7  
1 5  
R E F E R E N C E S ............................................................................................. 5 7  
1 6  
SI G N A T U R E S .............................................................................................. 5 8  
1 6. 1  
I n vesti g at or Si g n at ure .......................................................................... 5 8 
1 6. 2  
S p o ns or Si g n at ure ................................................................................. 5 9  
A P P E N DI X I:  
U S E O F P RI O R A N D C O N C O MI T A N T M E DI C A TI O N S .... 6 0  
I n-te xt Fi g ures 
Fi g ure 4- 1:  
St u d y Desi g n Dia gra m ............................................................................ 2 5  
Fi g ure 7- 1:  
Brist ol St o ol F or m Scale ( Le wis 1 9 9 7) .................................................. 3 7  
I n-te xt T a bles 
Ta ble 1- 1: 
Sc he d ule of Assess me nts a n d Pr oce d ures ( Part A a n d Part B) ............... 1 5  
Ta ble 7- 1:  
Cli nical La b orat or y Tests........................................................................ 3 9  
Ta ble 8- 1:  
A p pr o xi mate Bl o o d V ol u me per Patie nt ( Parts A a n d B 
C o m bi ne d) .............................................................................................. 5 0  


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L 
Pa ge 5 
1  
G E N E R A L I N F O R M A TI O N 
1. 1  
St u d y A d mi nistr a ti ve Str uct ure 
A Ra n d o mize d, O pe n- La bel St u d y t o  E val uate t he Use of Te na pan or as t he C ore T hera p y i n 
t he Treat me nt of H y per p h os p hatemia i n Patie nts wit h C hr o nic Ki d ne y Disease o n Dial ysis 
w h o are P h os p hate Bi n der Naï ve or o n P h os p hate Bi n der T hera p y, t o O pti mize P h os p h or us 
Ma na ge me nt ( O P TI MI Z E) 
 
 
Pr ot oc ol N o.: 
T E N- 0 2- 4 0 2 
 
S p o ns or: 
Ar del y x, I nc. 
S p o ns or’s C o ntact: 
 
 
 
Ar del y x, I nc. 
3 4 1 7 5 Ar de n w o o d Bl v d. 
Fre m o nt, C A 9 4 5 5 5 
 
 
 
 
 
Me dical M o nit or: 
 
 
 
Cli nical Researc h Or ga ni zati o n:   
 
  
 
 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L 
Pa ge 6 
1. 2  
S y n o psis 
Pr ot oc ol Title: 
A ra n d o mize d, o pe n-la bel st u d y t o e val uate t he use of te na pa n or as t he 
c ore t hera p y i n t he treat me nt of h y per p h os p hate mia i n patie nts wit h 
c hr o nic ki d ne y disease o n dial ysis w h o are p h os p hate bi n der naï ve or o n 
p h os p hate bi n der t hera p y, t o o pti mize p h os p h or us ma na ge me nt 
( O P TI MI Z E)  
S p o ns or: 
Ar del y x, I nc. 
St u d y P h ase: 
P hase 4 
O bjecti ves: 
T he pri mar y o bjecti ve of t his st u d y is: 
 
T o e val uate t he effect of te na pa n or al o ne or i n c o m bi nati o n wit h 
p h os p hate bi n ders t o ac hie ve tar get  ser u m p h os p h or us (s- P) le vels of 
≤5. 5 m g/ d L w he n te na pa n or is a d mi nistere d as t he c ore t hera p y 
(al o ne or i n c o m bi nati o n wit h p hos p hate bi n ders) f or t he treat me nt 
of h y per p h os p hate mia i n patie nts wit h c hr o nic ki d ne y disease 
( C K D) o n dial ysis. 
T he sec o n dar y o bjecti ves of t his st u d y, f or t he treat me nt of 
h y per p h os p hate mia i n C K D patie nt s o n dial ysis w h o are p h os p hate 
bi n der naï ve or o n p h os p hate bi n der t hera p y, i ncl u de:  
 
T o e val uate t he effect of te na pa n or al o ne or i n c o m bi nati o n wit h 
p h os p hate bi n ders t o ac hie ve vari o us s- P le vels (e. g., ≤4. 5 m g/ d L). 
 
T o e val uate differe nt strate gies of  i nitiati n g te na pa n or f or t he c o ntr ol 
of s- P le vel. 
 
T o e val uate t he effect of differe nt strate gies of i nitiati n g te na pa n or 
o n st o ol fre q ue nc y a n d c o nsiste nc y usi n g a dail y e Diar y. 
 
T o e val uate t he effect of te na pa n or o n re d uci n g dail y p h os p h or us-
l o weri n g t hera p y pill b ur de n ( n u m ber of pills a n d t otal pill wei g ht) 
w he n patie nts are starte d o n or tra nsiti o ne d t o te na pa n or fr o m 
c urre nt p h os p hate bi n der t hera p y. 
 
T o e val uate t he i m pact of patie nt e d ucati o n a n d use of sta n dar d of 
care me dicati o n o n t he t olera bilit y ma na ge me nt of te na pa n or. 
 
T o e val uate t he t olera bilit y of te na pa n or w he n patie nts are starte d o n 
or tra nsiti o ne d t o te na pa n or fr o m c urre nt p h os p hate bi n der t hera p y. 
 
T o e val uate patie nt e x perie n ce wit h p h os p h or us ma na ge me nt 
r o uti ne d uri n g st u d y c o m pare d t o bef ore st u d y. 
 
T o e val uate t he effect of te na pa n or al o ne or i n c o m bi nati o n wit h 
p h os p hate bi n ders o n i ntact fi br o blast gr o wt h fact or 2 3 (i F G F 2 3) 
a n d parat h yr oi d h or m o ne ( P T H). 
 
T o e val uate t he effect of te na pa n or al o ne or i n c o m bi nati o n wit h 
p h os p hate bi n ders o n t he use of P T H- m o dif yi n g me dicati o ns 
 
N u m ber of Sites: 
A p pr o xi matel y 4 0 sites 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L 
Pa ge 7 
Pl a n ne d S a m ple Size: 
A p pr o xi matel y 3 3 0 C K D patie nts o n dial ysis wit h h y per p h os p hate mia 
( > 4. 5 m g/ d L) will be e nr olle d i n t his st u d y.   
St u d y Desi g n: 
T his is a ra n d o mize d, o pe n-la bel st u d y t o e val uate differe nt met h o ds of 
i nitiati n g te na pa n or t hera p y i n C K D patie nts o n dial ysis wit h 
h y per p h os p hate mia, w he n t he y are eit her p h os p hate bi n der naï ve or o n 
p h os p hate bi n der t hera p y.        
T he st u d y c o nsists of a Scree ni n g vi sit, a 1 0- wee k o pe n-la bel Treat me nt 
Peri o d ( Part A), a n d a n o pti o nal 1 6- wee k o pe n-la bel E xte nsi o n Peri o d 
( Part B).  
 
Patie nts wit h s- P > 5. 5 a n d ≤1 0. 0 m g/ d L u n der sta ble p h os p hate 
bi n der treat me nt are ra n d o mize d i n a 1: 1 rati o t o t w o differe nt 
treat me nt c o h orts:  
o  C o h ort 1 (strai g ht s witc h), w h ic h st o ps ta ki n g p h os p hate 
bi n ders a n d is starte d o n te na pa n or 3 0 m g t wice dail y 
( BI D) at Visit 2 ( Da y 1);  
o  C o h ort 2, w hic h decreases p h os p hate bi n der d ose b y at 
least 5 0 % ( ma y be m ore t ha n 5 0 % if patie nt is ta ki n g a n 
o d d n u m ber of bi n der pills eac h da y), wit h a bilit y t o 
s witc h t he bi n der re gi me n fr o m t hrice dail y ( TI D) t o BI D 
or Q D; a n d i nitiates te na pa n or 3 0 m g BI D at Visit 2 
( Da y 1).  
 
P h os p hate bi n der naï ve patie nts wit h s- P > 4. 5 a n d ≤1 0. 0 m g/ d L 
are e nr olle d as C o h ort 3 a n d recei ve te na pa n or at Visit 2 ( Da y 1) 
wit h a starti n g d ose of 3 0 m g BI D. 
T he Scree ni n g visit ( Visit 1) m ust be sc he d ule d at t he first s h ort dial ysis 
i nter val of t he wee k ( We dnes da y or T h urs da y), t he 
Ra n d o mizati o n/ E nr oll me nt visit ( Visit 2) m ust be sc he d ule d t w o da ys 
after t he Scree ni n g visit at t he sec o n d s h ort dial ysis i nter val of t he wee k 
( Fri da y or Sat ur da y), a n d all ot her visits i n t he st u d y m ust be sc he d ule d 
after a s h ort dial ysis i nter val ( We d nes da y or Fri da y f or patie nts o n a 
M o n da y- We d nes da y- Fri da y sc he d ule a n d T h urs da y or Sat ur da y f or 
patie nts o n a T ues da y- T h urs da y- Sat ur da y sc he d ule pr o vi de d t he patie nt 
has n ot misse d a n y dial ysis treat me nt or altere d t heir sc he d ule). B o d y 
wei g ht, vital si g ns, a n d bl o o d c oll ecti o ns f or la b orat or y assess me nts 
m ust  be perf or me d pre- dial ysis ( pri or t o dial ysis at t he visit). All ot her 
assess me nts ma y be perf or me d pre-, d uri n g, or p ost- dial ysis b ut s h o ul d 
be perf or me d at t he sa me ti me at eac h visit a n d t he sa me da y as dial ysis.  
T he e nr oll me nt criteria o n s- P will be e val uate d base d o n t he s- P 
meas ure d at t he Scree ni n g visit ( V isit 1) al o ne ( C o h ort 3 o nl y: bi n der 
naï ve) or t o get her wit h t he m ost rece nt s- P meas ure me nt pri or t o t he 
Scree ni n g visit ( Visit 1): 
 
Patie nts o n p h os p hate bi n der t h era p y m ust recei ve p h os p hate 
bi n der(s) t hrice dail y, a n d b ot h t he s- P le vel assesse d at t he m ost 
rece nt meas ure me nt pri or t o t he Scree ni n g visit ( Visit 1) a n d t he 
s- P le vel assesse d at t he Scree ni n g visit ( Visit 1) m ust be > 5. 5 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L 
Pa ge 8 
a n d ≤1 0. 0 m g/ d L t o q ualif y f or ra n d o mizati o n i nt o C o h ort 1 or 
C o h ort 2 at Visit 2 ( Da y 1).  

P h os p hate bi n der naï ve patie nts m u st ha ve t he s- P le vel assesse d
at t he Scree ni n g visit ( Visit 1) > 4. 5 a n d ≤1 0. 0 m g/ d L t o q ualif y
f or e nr oll me nt i nt o C o h ort 3 at Visit 2 ( Da y 1).
Patie nts w h o d o n ot meet t he ra n d o mizati o n/e nr oll me nt criteria o n s- P 
will be disc o nti n ue d as scree n fail ures. Patie nts m ust c o nti n ue t o meet all 
ot her a p plica ble i ncl usi o n/e xcl usi o n criteria at Visit 2 ( Da y 1) i n or der t o 
be ra n d o mize d i nt o C o h ort 1 or 2 or be e nr olle d i n C o h ort 3.  
Patie nts will be e d ucate d at Scree ni n g ( Visit 1) a n d 
Ra n d o mizati o n/ E nr oll me nt ( Visit 2) a b o ut te na pa n or, h o w t o ta ke 
te na pa n or, w hat t he y ma y e x perie nce o n te na pa n or, me dicati o ns t o be 
disc o nti n ue d bef ore starti n g te na pa n or, a n d h o w best t o ma na ge a 
p ossi ble i ncrease i n b o wel m o ve me nt fre q ue nc y a n d/ or l o ose st o ol if 
b ot hers o me (e. g., use of o ver-t he-c o u nter a nti- diarr heal), etc. 
I n or der t o assess t he t olera bilit y pr ofile of te na pa n or al o ne or c o m bi ne d 
wit h p h os p hate bi n ders, patie nts will use a dail y electr o nic diar y (e Diar y) 
t o rec or d dail y b o wel ha bits (st o ol fre q ue nc y a n d st o ol c o nsiste nc y) 
t hr o u g h o ut t he 1 0- wee k Treat me nt Peri o d, Part A. 
O n Da y 1 ( Visit 2), patie nts will start t o recei ve te na p a n or at a d ose of 
3 0 m g BI D. Te na pa n or will be ta ke n or all y BI D; j ust pri or t o brea kfast 
a n d di n ner. Patie nts s h o ul d n ot  ta ke st u d y dr u g at t he meal i m me diatel y 
prece di n g he m o dial ysis. T he I n vesti gat or ma y titrate t he d ose of 
te na pa n or i n 1 0 m g i ncre me nts d o w n t o a mi ni m u m of 1 0 m g Q D or u p 
t o a ma xi m u m of 3 0 m g BI D at a n y ti me d uri n g t he st u d y base d o n s- P 
le vels a n d/ or gastr oi ntesti nal ( GI) t olera bilit y.  
If a p h os p hate bi n der is bei n g ta ke n b y a patie nt i n a n y of t he t hree 
c o h orts, it ca n be d ose d starti n g at eit her Q D or BI D or TI D: if ta ke n Q D, 
it s h o ul d be ta ke n wit h t he lar gest meal of t he da y; if ta ke n BI D, it s h o ul d 
be ta ke n wit h t he sa me meals te na pa n or  is ta ke n wit h. T he I n vesti gat or 
ma y decrease t he d ose of p h os p hate bi n der at a n y ti me d uri n g t he st u d y 
base d o n s- P le vels. H o we ver, d ose u p- titrati o n f or p h os p hate bi n der is 
n ot all o we d fr o m Da y 1 ( Visit 2) u n til Wee k 2 of t he Treat me nt Peri o d 
( Visit 4). Starti n g fr o m Visit 4, t he I n vesti gat or ma y i ncrease t he d ose of 
p h os p hate bi n der or a d d p h os p hate bi n der base d o n s- P le vels; t he d ose 
of a p h os p hate bi n der ca n be titrate d u p t o t he ma xi m u m d ose TI D per 
t he c orres p o n di n g p h os p hate bi n der pac k a ge i nsert, if nee de d, base d o n 
s- P le vels.
If decreasi n g t he d ose of te na pa n or or p h os p hate bi n der d ue t o l o w s- P 
le vels, t he p h os p hate bi n der d ose s h o uld be decrease d pri or t o decreasi n g 
t he te na pa n or d ose u ntil patie nt is n o l o n ger ta ki n g a n y p h os p hate bi n der. 
If i ncreasi n g t he d ose of te na pa n or or p h os p hate bi n der d ue t o hi g h s- P 
le vels, t he te na pa n or d ose s h o ul d be i ncrease d pri or t o i ncreasi n g t he 
p h os p hate bi n der d ose u ntil t he te na pa n or d ose reac hes 3 0 m g BI D or 
ca n n ot be i ncrease d d ue t o GI t olera bilit y  at t he I n vesti gat or’s discreti o n. 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L 
Pa ge 9 
Rec o m me n de d d ose a dj ust me nts base d o n s- P le vels d uri n g t he st u d y are 
s pecifie d bel o w f or eac h c o h ort:  
I n C o h ort 1 (strai g ht s witc h t o te na pa n or),  
 
If t he patie nt’s s- P assesse d at or after Visit 4 ( Wee k 2) is 
> 5. 5 m g/ d L, t he I n vesti gat or ma y a d d o ne p h os p hate bi n der pill 
dail y ( Q D) ( wit h lar gest meal) or o ne p h os p hate bi n der pill BI D 
(at sa me meals as te na pa n or). T he p h os p hate bi n der d osi n g 
re gi me n s h o ul d start at Q D or BI D; a n d t he d ose of p h os p hate 
bi n der ca n be titrate d u p t o t he ma xi m u m d ose TI D per t he 
c orres p o n di n g p h os p hate bi n der pac ka ge i nsert, if nee de d. W he n 
p h os p hate bi n der is bei n g a d de d t o  C o h ort 1, t he I n vesti gat or 
s h o ul d use t he p h os p hate bi n der t he patie nt st o p pe d at t he 
be gi n ni n g of t he st u d y. 
 
If t he patie nt is ta ki n g p h os p hate bi n der a n d his/ her s- P is 
< 5. 0 m g/ d L, t he I n vesti gat or ma y re m o ve o ne or t w o p h os p hate 
bi n der pills fr o m t he patie nt’s dail y re gi me n. 
 
If t he patie nt is ta ki n g n o p h osp hate bi n der a n d his/ her s- P is 
≤3. 5 m g/ d L, t he d ose of te na pa n or s h o ul d be decrease d b y 1 0 m g 
BI D. If t he patie nt is ta ki n g te na pa n or 1 0 m g BI D, t he n t he d ose 
of te na pa n or s h o ul d be decrease d t o 1 0 m g Q D. 
I n C o h ort 2 ( 5 0 % p h os p hate bi n der re d ucti o n),  
 
T he re d uce d p h os p hate bi n der d ose ca n be d ose d starti n g at Q D, 
BI D or TI D wit h meals: if ta ke n Q D, it s h o ul d be ta ke n wit h t he 
lar gest meal of t he da y; if ta ke n BI D, it s h o ul d be ta ke n wit h t he 
sa me meals te na pa n or is ta ke n. 
 
If t he patie nt’s s- P is > 5. 5 m g/ d L, t he I n vesti gat or ma y a d d o ne 
p h os p hate bi n der pill Q D ( wit h la r gest meal) or o ne p h os p hate 
bi n der pill BI D (at sa me meals as te na pa n or). T he d ose of 
p h os p hate bi n der ca n be titrate d u p t o t he ma xi m u m d ose TI D 
per t he c orres p o n di n g p h os p hate bi n der pac ka ge i nsert, if 
nee de d. 
 
If t he patie nt’s s- P is < 5. 0 m g/ dL, t he I n vesti gat or ma y re m o ve 
o ne or t w o p h os p hate bi n der p ills fr o m t he patie nt’s dail y 
re gi me n. 
 
If t he patie nt is ta ki n g n o p h osp hate bi n der a n d his/ her s- P is 
≤3. 5 m g/ d L, t he d ose of te na pa n or s h o ul d be decrease d b y 1 0 m g 
BI D. If t he patie nt is ta ki n g te na pa n or 1 0 m g BI D, t he n t he d ose 
of te na pa n or s h o ul d be decrease d t o 1 0 m g Q D. 
I n C o h ort 3 ( p h os p hate bi n der naï ve),  
 
If t he patie nt’s s- P assesse d at or after Visit 4 ( Wee k 2) is 
> 5. 5 m g/ d L, t he I n vesti gat or ma y a d d o ne p h os p hate bi n der pill 
Q D ( wit h lar gest meal) or o ne p h os p hate bi n der pill BI D (at 
sa me meals as te na pa n or). T he p h os p hate bi n der d osi n g re gi me n 
s h o ul d start at Q D or BI D; a n d t he d ose of p h os p hate b i n der ca n 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L 
Pa ge 1 0 
be titrate d u p t o t he ma xi m u m d ose TI D per t he c orres p o n di n g 
p h os p hate bi n der pac ka ge i nsert, if  nee de d. T he I n vesti gat or ca n 
c h o ose a n y bra n d of p h os p hate bi n der. 
 
If t he patie nt is ta ki n g p h os p hate bi n der after Visit 4 ( Wee k 2) 
a n d his/ her s- P assesse d aft er t he bi n der use is < 5. 0 m g/ d L, t he 
I n vesti gat or ma y re m o ve o ne or m ore p h os p hate bi n der pills 
fr o m t he patie nt’s re gi me n. 
 
If t he patie nt is ta ki n g n o p h osp hate bi n der a n d his/ her s- P is 
≤3. 5 m g/ d L, t he d ose of te na pa n or s h o ul d be decrease d b y 1 0 m g 
BI D. If t he patie nt is ta ki n g te na pa n or 1 0 m g BI D, t he n t he d ose 
of te na pa n or s h o ul d be decrease d t o 1 0 m g Q D. 
Safet y assess me nts will be perf or me d  at vari o us ti me p oi nts t hr o u g h o ut 
t he st u d y ( Sc he d ule of Assess me nts a n d Pr oce d ures [ Part A a n d Part B] 
Ta ble 1- 1 ) a n d will i ncl u de a d verse e ve nt ( A E) rec or di n g, p h ysical 
e xa mi nati o n, b o d y wei g ht, vital si g ns, 1 2-lea d electr o car di o gra m ( E C G), 
a n d safet y la b orat or y tests (r o uti ne ser u m c he mistr y a n d he mat ol o g y). 
St o ol fre q ue nc y a n d st o ol c o nsiste nc y will be c ollecte d usi n g a dail y 
e Diar y t hr o u g h o ut t he 1 0- wee k Treat me nt Peri o d ( Part A o nl y) as 
t olera bilit y meas ures.   
Bl o o d sa m ples will be c ollecte d t o meas ure s- P, i F G F 2 3, P T H, a n d 
cli nical la b orat or y c he mistr y a n d he mat ol o g y tests; a d diti o nal sa m ples 
will be st ore d, as a p pr o priate, f or t h e p ote ntial e val uati o n of e x pl orat or y 
bi o mar kers.  
Tre at me nt D ur ati o n 
T he d urati o n of treat me nt i n t his st u d y will be u p t o 2 6 wee ks; i ncl u di n g 
a 1 0- wee k Treat me nt Peri o d ( Part A) a n d a n o pti o nal 1 6- wee k E xte nsi o n 
Peri o d ( Part B). 
Eli gi bilit y Criteri a:  
I ncl usi o n Criteri a: 
1.  
Si g ne d a n d date d i nf or me d c o nse nt f or m pri or t o a n y st u d y 
s pecific pr oce d ures. 
2.  
Males or fe males a ge d 1 8 t o 8 0 years, i ncl usi ve, at Scree ni n g 
( Visit 1). 
3.  
Fe males m ust be n o n- pre g na nt a n d n o n-lactati n g. 
4.  
Patie nts o n p h os p hate bi n der t hera p y m ust be o n c hr o nic 
mai nte na nce he m o dial ysis ( H D) 3 ti mes per wee k f or at least 
3 m o nt hs or c hr o nic mai nte na nce perit o neal dial ysis ( P D) f or a 
mi ni m u m of 6 m o nt hs. If m o dalit y of dial ysis has c h a n ge d, t he 
patie nt m ust meet o ne of t he t w o dial ysis criteria a b o ve a n d bee n 
o n t he ne w m o dalit y of dial ysis f or a mi ni m u m of o ne m o nt h. 
P h os p hate bi n der naï ve patie nts m ust be o n c hr o nic mai nte na nce 
H D 3 ti mes p er wee k or c hr o nic mai nte na nce P D. 
5.  
Kt/ V ≥1. 2 at m ost rece nt meas ure me nt pri or t o Scree ni n g ( Visit 
1). 
6.  
Prescri be d a n d ta ki n g p h os p hate bi n der me dicati o n at least 
3 ti mes per da y or bei n g p h os p ha te bi n der naï ve; defi ne d as 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L 
Pa ge 1 1 
ha vi n g n ot ta ke n p h os p hate bi n ders f o r at least 3 m o nt hs pri or t o 
Scree ni n g. T he patie nt m ust be ta ki n g a mi ni m u m of 6 pills per 
da y f or Re n vela, A ur y xia, or P h os L o; a n d/ or a mi ni m u m of 
3 pills per da y f or F osre n ol or Vel p h or o. 
7.  
F or patie nts ta ki n g p h os p hate bi n ders, b ot h t he s- P le vel at t he 
m ost rece nt meas ure me nt pri or t o Scree ni n g ( Visit 1) a n d t he s- P 
le vel at Scree ni n g ( Visit 1) m ust be > 5. 5 a n d ≤1 0. 0 m g/ d L. 
8.  
F or p h os p hate bi n der naï ve patie nts, t he s- P le vel at Scree ni n g 
( Visit 1) m ust be > 4. 5 a n d ≤1 0. 0 m g/ d L.  
9.  
A ble t o u n dersta n d a n d c o m pl y wit h t he pr ot oc ol. 
E xcl usi o n Criteri a: 
1.  
Se vere h y per p h os p hate mia defi ne d as ha vi n g a n s- P le vel > 1 0. 0 
m g/ d L at a n y ti me p oi nt d uri n g r o uti ne cli nical m o nit ori n g f or 
t he 3 prece di n g m o nt hs bef ore Scree ni n g ( Visit 1). 
2.  
Ser u m/ plas ma P T H > 1 2 0 0 p g/ m L. T he m ost rece nt val ue fr o m 
t he patie nt’s me dical rec or ds s h o ul d be use d. 
3.  
Cli nical si g ns of h y p o v ole mia at Scree ni n g ( Visit 1) as j u d ge d b y 
t he I n vesti gat or. 
4.  
Hist or y of i nfla m mat or y b o wel disease or irrita ble b o wel 
s y n dr o me wit h diarr hea. 
5.  
Sc he d ule d f or li vi n g d o n or ki d ne y tra ns pla nt or pla ns t o rel ocate 
t o a n ot her ce nter d uri n g t he st u d y. 
6.  
Use of a n i n vesti gati o nal a ge nt wit hi n 3 0 da ys pri or t o Scree ni n g 
( Visit 1). 
7.  
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 Ar del y x/ C o ntract Researc h Or g a nizati o n ( C R O) staff 
a n d/ or staff at t he st u d y site).  
8.  
If, i n t he o pi ni o n of t he I n vesti gat or, t he patie nt is u na ble or 
u n willi n g t o f ulfill t he re q uire me nts of t he pr ot oc ol or has a 
c o n diti o n w hic h w o ul d re n der t he res ults u ni nter preta ble. 
St u d y Dr u g: 
Te na pa n or 1 0, 2 0, a n d/ or 3 0 m g ta blets  
S afet y, T oler a bilit y, 
a n d Effic ac y 
Me as ures: 
S afet y Me as ures:  
A E m o nit ori n g; p h ysical e xa mi nati o n; b o d y wei g ht; vital si g ns; 1 2-lea d 
E C G; a n d safet y la b orat or y tests (r o uti ne ser u m c he mistr y a n d 
he mat ol o g y)  
 
T oler a bilit y Me as ures:   
St o ol fre q ue nc y a n d st o ol c o nsiste nc y c ollecte d usi n g a dail y e Diar y 
t hr o u g h o ut t he 1 0- wee k Treat me nt Peri o d ( Part A o nl y)   
 
Effic ac y Me as ures: 
Ser u m p h os p h or us, i F G F 2 3, P T H, me dicati o n d ose, pill n u m ber, pill 
wei g ht, a n d ot her i nf or mati o n relati ve t o dr u g usa ge (e. g., % o n 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L 
Pa ge 1 2 
m o n ot hera p y) a n d patie nt e x perie nce   
St atistic al A n al yses:  
A n al ysis P o p ul ati o ns: 
 
I nte nt-t o- Tre at (I T T) P o p ul ati o n: will i ncl u de all ra n d o mize d 
or e nr olle d patie nts. 
 
S afet y P o p ul ati o n:  will i ncl u de all I T T patie nts w h o recei ve at 
least o ne d ose of st u d y dr u g. It will be t he a nal ysis p o p ulati o n f or 
safet y a n d t olera bilit y a nal yses.  
 
F ull A n al ysis Set ( F A S):  will i ncl u de all I T T patie nts w h o meet 
t he st u d y e ntr y eli gi bilit y criteria, recei v e at least o ne d ose of 
st u d y dr u g, a n d ha ve at least o ne p ost- baseli ne s- P meas ure me nt 
d uri n g t he st u d y. It will be t he a nal ysis p o p ulati o n f or efficac y 
a nal yses.   
 
F A S ( C o h orts 1- 2): will i ncl u de all F A S patie nts i n C o h ort 1 
a n d C o h ort 2. It will be t he a nal ysis p o p ulati o n f or a nal yses of 
efficac y e n d p oi nts a p plica ble t o C o h ort 1 a n d C o h ort 2 o nl y. 
S afet y A n al yses: 
All safet y a n d t olera bilit y meas ures will be s u m mari ze d descri pti vel y b y 
c o h ort a n d f or t he e ntire Safet y P o p ulati o n. Treat me nt-e mer ge nt A Es will 
be s u m marize d b y Me d D R A s yste m or g a n class a n d preferre d ter m. 
St o ol fre q ue nc y a n d c o nsiste nc y c ollect e d o n a dail y basis t hr o u g h o ut t he 
st u d y will be s u m marize d o n a wee kl y basis (i.e., a vera g e wee kl y st o ol 
fre q ue nc y a n d a vera ge wee kl y st o ol c o nsiste nc y). 
Effic ac y A n al yses: 
All efficac y meas ures will be s u m mari ze d descri pti vel y b y c o h ort a n d f or 
t he e ntire F A S.  
T he f oll o wi n g efficac y e n d p oi nts w ill be s u m marize d descri pti vel y b y 
c o h ort a n d f or t he e ntire F A S at eac h p ost- baseli ne visit ( o nl y f or s- P 
e n d p oi nts), t he e n d p oi nt visit of t he Treat me nt Peri o d, a n d t he e n d p oi nt 
visit of t he e ntire st u d y:  
 
s- P res p o nse: ac hie vi n g or mai ntai ni n g s- P ≤5. 5 m g/ d L 
 
N or mal s- P res p o nse: ac hi e vi n g s- P ≤4. 5 m g/ d L 
 
B or derli ne s- P res p o nse: ac hie vi n g or mai ntai ni n g s- P ≤6. 5 
m g/ d L 
 
C ha n ge fr o m baseli ne i n s- P 
 
Relati ve c ha n ge fr o m baseli ne i n  i F G F 2 3, deri ve d as “c ha n ge 
fr o m baseli ne i n i F G F 2 3/ baseli ne i F G F 2 3” 
 
C ha n ge fr o m baseli ne i n P T H 
 
C ha n ge fr o m baseli ne i n t otal dail y d ose of P T H- m o dif yi n g 
me dicati o ns ( m g) 
 
T he f oll o wi n g efficac y e n d p oi nts will als o b e s u m marize d descri pti vel y 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L 
Pa ge 1 3 
b y c o h ort a n d f or t he e ntire “ F A S ( C o h orts 1- 2)” at eac h p ost- baseli ne 
visit, t he e n d p oi nt visit of t he Treat me nt Peri o d, a n d t he e n d p oi nt visit of 
t he e ntire st u d y f or patie nts s witc hi n g t heir p h os p hate bi n der t hera p y t o 
te na pa n or t hera p y: 
 
C ha n ge fr o m baseli ne i n t otal dail y d ose of p h os p h or us-l o weri n g 
me dicati o n ( m g) (te na pa n or a n d p h os p hate bi n der c o m bi ne d) 
 
C ha n ge fr o m baseli ne i n t otal dail y pill wei g ht (te na pa n or a n d 
p h os p hate bi n der c o m bi ne d)  
 
C ha n ge fr o m baseli ne i n t otal da il y pill n u m ber (te na pa n or a n d 
p h os p hate bi n der c o m bi ne d) 
 
Me dicati o n d ose res p o nse: ac hie vi n g at least 3 0 % re d ucti o n fr o m 
baseli ne i n t otal dail y d ose ( m g) of p h os p h or us-l o weri n g 
me dicati o n 
 
Pill wei g ht res p o nse: ac hie vi n g at least 3 0 % re d ucti o n fr o m 
baseli ne i n t otal dail y pill wei g ht  
 
Pill n u m ber res p o nse: ac hi e vi n g at least 3 0 % re d ucti o n fr o m 
baseli ne i n t otal dail y pill n u m ber (e. g., re d uce fr o m 6 pills at 
baseli ne t o ≤4 pills a n d re d uce fr o m 9 pills at baseli ne t o  
≤6 pills) 
 
Pill b ur de n res p o nse: ac hie vi n g pill wei g ht res p o nse a n d pill 
n u m ber res p o nse 
 
s- P a n d me dicati o n d ose res p o nse: ac hie vi n g s- P res p o nse a n d 
me dicati o n d ose res p o nse 
 
s- P a n d pill wei g ht res p o nse: ac hie vi n g s- P res p o nse a n d pill 
wei g ht res p o nse 
 
s- P a n d pill n u m ber res p o nse: ac hie vi n g s- P res p o nse a n d pill 
n u m ber res p o nse 
 
s- P a n d pill b ur de n res p o nse: ac hie vi n g s- P res p o nse, pill wei g ht 
res p o nse, a n d pill n u m ber res p o nse  
 
N or mal s- P a n d me dicati o n d ose res p o nse: ac hie vi n g n or mal s- P 
res p o nse a n d me dicati o n d ose res p o nse 
 
N or mal s- P a n d pill wei g ht res p o nse: ac hie vi n g n or mal s- P 
res p o nse a n d pill wei g ht res p o nse 
 
N or mal s- P a n d pill n u m ber res p o nse: ac hie vi n g n or mal s- P 
res p o nse a n d pill n u m ber res p o nse 
 
N or mal s- P a n d pill b ur de n res p o nse: ac hie vi n g n or mal s- P 
res p o nse, pill wei g ht res p o nse, a n d pill n u m ber res p o nse 
 
B or derli ne s- P a n d me dicati o n d ose res p o nse: ac hie vi n g 
b or derli ne s- P res p o nse a n d me dicati o n d ose res p o nse 
 
B or derli ne s- P a n d pill wei g ht res p o nse: ac hie vi n g b or derli ne s- P 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L 
Pa ge 1 4 
res p o nse a n d pill wei g ht res p o nse 
 
B or derli ne s- P a n d pill n u m ber res p o nse: ac hie vi n g b or derli ne s-
P res p o nse a n d pill n u m ber res p o nse 
 
B or derli ne s- P a n d pill b ur de n res p o nse: ac hie vi n g b or derli ne s- P 
res p o nse, pill wei g ht res p o nse, a n d pill n u m ber res p o nse 
 
T he fi nal list of efficac y e n d p oi nts will be pr o vi de d i n t he statistical 
a nal ysis pla n.  
E x pl orat or y i nfere ntial a nal yses ma y be perf or me d t o c o m pare efficac y 
e n d p oi nts bet wee n c o h orts. S u b gr o u p a nal yses b y a ge, se x, race, 
p h os p hate bi n der t y pe, baseli ne s- P,  a n d e n di n g t hera p y cate g or y (e. g., 
te na pa n or al o ne, te na pa n or + ≤3 ta blets/ da y p h os p hate bi n der, or 
te na pa n or + > 3 ta blets/ da y p h os p hate bi n der) will be perf or me d f or 
selecti ve e n d p oi nts. 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L 
Pa ge 1 5 
1. 3  
Sc he d ule of Assess me nts a n d Pr oce d ures 
T a ble 1- 1:   
Sc he d ule of Assess me nts a n d Pr oce d ures ( P art A a n d P art B) 
P art A - Scree ni n g a n d Tre at me nt Peri o d 
 
Scree ni n g a 
10 -W eek  T rea tm en t P erio d  b  
 
Visit 1  
Visit 2  
Visit 3  
Visit 4  
Visi t 5  
Visit 6  
Visit 7  
Visit 8  
Visit 9c 
 
Da y  -2  
D a y  1  
W eek  1  
W eek  2  
W eek  3  
Wee k 4  
Wee k 6  
Wee k 8  
Wee k 1 0 
St u d y D a y/ Visit Wi n d o w  
-2  
1d 
8 ± 2 
1 5 ± 2 
2 2 ± 2 
2 9 ± 2 
4 3 ± 2 
5 7 ± 2 
7 1 ± 2 
St u d y Pr oce d ure  
 
 
 
 
 
 
 
 
 
I nf or me d C o nse nt 
X 
 
 
 
 
 
 
 
 
I ncl usi o n/ E xcl usi o n Criteria 
X  
X e 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ra n d o mizati o n/ E nr oll me nt 
 
X a 
 
 
 
 
 
 
 
 
 
 
 
 
 
De m o gra p hics 
X 
 
 
 
 
 
 
 
 
Me dical/ S ur gical Hist or y  
X  
X f 
 
 
 
 
 
 
 
Pri or/ C o nc o mita nt Me dicati o ns g 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Patie nt E d ucati o n h 
X 
X  
 
 
 
 
 
 
 
e Diar y i I nstr ucti o ns. 
X 
X 
 
 
 
 
 
 
 
e Diar y i C o m pleti o n Re vie w 
 
 
X 
X 
X 
X 
X 
X 
X 
P h ysical E xa mi nati o n 
X 
 
 
 
 
 
 
 
X 
Wei g ht ( pre- dial ysis) 
X 
 
 
 
 
 
 
 
X 
Hei g ht 
X 
 
 
 
 
 
 
 
 
Vital Si g ns j 
X 
 
 
 
 
 
 
 
X  
1 2-lea d E C G 
X 
 
 
 
 
 
 
 
X 
Safet y La b orat or y E val uati o ns k 
X 
 
 
 
 
 
 
 
X 
Ser u m P h os p h or us 
X 
 
X 
X 
X 
X 
X 
X 
X 
F S H Test l 
X 
 
 
 
 
 
 
 
 
Pre g na nc y Test l 
X 
 
 
 
 
 
 
 
X  
St u d y Dr u g Dis pe nse 
 
X 
X 
X 
X 
X 
X 
X 
X 
St u d y Dr u g Ret ur n/acc o u nta bilit y 
 
 
X 
X 
X 
X 
X 
X 
X 
i F G F 2 3, P T H Bl o o d Sa m ple 
X 
 
 
 
 
 
 
 
X 
Bi o mar ker Bl o o d Sa m ple 
X 
 
 
 
 
 
 
 
X 
A E Assess me nt 
 
X 
X 
X 
X 
X 
X 
X 
X 
Patie nt E x perie nce Assess me nt m 
 
 
 
 
 
 
 
 
X 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L 
Pa ge 1 6 
P art B - O pti o n al E xte nsi o n Peri o d 
1 6- Wee k E xte n si o n Peri o d b
St art of 
P art B  
Visit 9 
Visit 1 0  
Visit 1 1 
Visit 1 2  
Visit 1 3 c 
Wee k  1 0  
Wee k 1 4  
Wee k 1 8  
Wee k 2 2  
Wee k 2 6 
St u d y D a y/ Visit Wi n d o w  
7 1 ± 2  
9 9 ± 7  
1 2 7 ± 7  
1 5 5 ± 7  
1 8 3 ± 7 
St u d y Pr oce d ure
Pri or/ C o nc o mita nt Me dicati o ns g
X
X
X
X
X  
P h ysical E xa mi nati o n
X
X  
Wei g ht ( pre- dial ysis)
X
X  
Vital Si g ns j
X
X  
1 2-lea d E C G
X
X  
Safet y La b orat or y E val uati o ns k
X
X  
Ser u m P h os p h or us
X
X
X
X
X  
Pre g na nc y Test l
X
X  
St u d y Dr u g Dis pe nse 
X 
X 
X 
X 
St u d y Dr u g Ret ur n/acc o u nta bilit y 
X 
X 
X 
X 
X  
i F G F 2 3, P T H Bl o o d Sa m ple 
X 
X  
Bi o mar ker Bl o o d Sa m ple 
X 
X  
A E Assess me nt
X
X
X
X
X  
Patie nt E x perie nce Assess me nt m
X
a Scree ni n g visit will be o n t he first s h ort i nter val of t he wee k ( We d nes da y or T h urs da y). Ra n d o mizati o n/e nr oll me nt will be 2 da y s after t he scree ni n g visit ( Fri da y or Sat ur da y), if t he
patie nt meets all t he i ncl usi o n/e xcl usi o n criteria.
b All visits are after a s h ort i nter val ( We d nes da y or Fri da y f or M, W, F dial ysis a n d T h urs da y or Sat ur da y f or T, T h, S dial ysis)
c All assess me nts a n d pr oce d ures at Visit 9 e xce pt st u d y dis pe nsi n g s h o ul d be perf o r me d at t he Earl y Ter mi nati o n visit f or patie nts w h o pre mat urel y disc o nti n ue fr o m t he st u d y bef ore
Visit 9; t h ose at Visit 1 3 s h o ul d be perf or m e d at t he Earl y Ter mi nati o n visit f or patie nts w h o pre mat urel y disc o nti n ue fr o m t he  st u d y bet wee n Visit 9 a nd Visit 1 3, if p ossi ble.
d Da y 1 is t he ra n d o mizati o n/e nr oll me nt da y a n d ser ves as  t he refere nce da y f or all p ost-ra n d o mizati o n visits.
e Patie nts m ust c o nti n ue t o meet all a p plica ble i ncl usi o n/e xcl usi o n criteria bef ore ra n d o mizati o n/e nr oll me nt, i ncl u di n g t he crite ria base d o n t he s- P le vel at Visit 2.
f
g
Rec or d o nl y c ha n ges t o me dical hist or y fr o m Visit 1
Refer t o  A p pe n di x I  f or a list of me dicati o ns t o be disc o nti n ue d bef ore starti n g te na pa n or, pr o hi bited c o nc o mita nt me dicati o ns,  P T H- m o dif yi n g me dicati o ns, a n d  me dicati o ns 
rec o m me n de d f or ma na gi n g c ha n ges i n  b o wel m o ve me nts d uri n g  t he st u d y. T hese me dicati o ns  will be c hec ke d at e ver y visit.  A n y ne w  P T H- m o dif yi n g me dicati o n use or  c ha n ges t o 
e xisti n g P T H- m o dif yi n g me dicati o n  use nee d  t o be ade q uatel y rec or de d i n  t he Pri or/ C o nc o mita nt Me dicati o ns e C R F.
h Patie nt e d ucati o n will i ncl u de i nf or mati o n a b o ut te na pa n or, h o w t o ta ke te na pa n or, w hat  t he y ma y e x perie nce o n te na pa n or, me dicati o ns t o be disc o nti n ue d bef ore starti n g te na pa n or,
a n d h o w best t o ma na ge a p ossi ble i ncrease i n b o wel m o ve me nt fr e q ue nc y a n d/ or l o ose st o ol if b others o me (e. g., use of o ver-t he- c o u nter a nti- diarr heal), etc.
i
T he dail y e Diar y will as k q ues ti o ns a b o ut a patie nt’s st o ol fre q ue nc y a n d st o ol c o nsiste nc y d uri n g t he past 2 4 h o urs. T he e Diary is c o m plete d d uri n g Part A of t he st u d y.


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L 
Pa ge 1 7 
j  Vital si g ns i ncl u de sitti n g or s u pi ne bl o o d press u re a n d p ulse, pri or t o dial ysis at t he visit. 
k  Safet y la b orat or y e val uati o ns will i ncl u de t he he mat ol o g y a n d ser u m c he mistr y tests. 
l  F S H ( p ost me n o pa usal fe males) a n d pre g na nc y tests are perf or me d o n all fe males < 6 0 year s of a ge u nless t here is a d oc u me nte d meth o d of sterilizati o n, or F S H test c o nfir ms p ost-
me n o pa usal stat us. 
m  Patie nt e x perie nce assess me nt will be c o n d ucte d via a n e P R O q ues ti o n naire a n d will i ncl u de q uesti o ns re gar di n g a patie nt’s e x perie nce wit h p h os p h or us mana ge me nt r o uti ne d uri n g 
st u d y c o m pare d t o bef ore st u d y. 
 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 1 8 of 6 0 
1. 4  
List of A b bre vi ati o ns 
A b bre vi ati o n  
Defi niti o n 
A E 
a d verse e ve nt 
A L T 
ala ni ne a mi n otra nsa mi nase 
A S T 
as partate a mi n otra nsa mi nase 
BI D 
bis e n die, t wice a da y 
B U N 
bl o o d urea nitr o ge n 
C F R 
C o de of Fe deral Re g ulati o ns ( U nite d States) 
C K D 
c hr o nic ki d ne y disease 
C R O 
c o ntract researc h or ga nizati o n 
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 me 
E S R D 
e n d-sta ge re nal disease 
F A S 
F ull A nal ysis Set 
F D A 
( U nite d States) F o o d a n d Dr u g A d mi nistrati o n 
F S H 
f ollicle-sti m ulati n g h or m o ne 
G C P 
G o o d Cli nical Practice 
GI 
gastr oi ntesti nal 
H D 
he m o dial ysis 
H D P E 
hi g h- de nsit y p ol yet h yle ne 
I B 
I n vesti gat or’s Br oc h ure 
I B S- C 
irrita ble b o wel s y n dr o me wit h c o nsti pati o n  
I C F 
i nf or me d c o nse nt f or m 
I C H 
I nter nati o nal C o m mittee o n Har m o nizati o n 
I E C 
I n de pe n de nt Et hics C o m mittee 
i F G F 2 3 
i ntact fi br o blast gr o wt h fact or 2 3 
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 
I T T 
i nte nt-t o-treat 
I U D 
i ntra uteri ne de vice 
Kt/ V 
a meas ure of dial ysis a de q uac y 
Me d D R A 
Me dical Dicti o nar y f or Dr u g Re g ulat or y Acti vities 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 1 9 of 6 0 
A b bre vi ati o n  
Defi niti o n 
N H E 3 
s o di u m- h y dr o ge n e xc ha n ger 3 
P D 
perit o neal dial ysis 
P R 
E C G i nter val fr o m P wa ve o nset t o Q R S c o m ple x o nset 
P T H 
parat h yr oi d h or m o ne 
Q D 
q ua q ue die, o nce a da y 
Q R S 
pri nci pal deflecti o n i n E C G 
Q T 
E C G i nter val 
Q Tc 
Q T i nter val w hic h has bee n c orrecte d b y ta ki n g i nt o acc o u nt heart rate 
R B C 
re d bl o o d cell 
R R 
E C G i nter val bet wee n t w o c o nsec uti ve R wa ves 
S A E 
seri o us a d verse e ve nt 
S A P 
statistical a nal ysis pla n 
S O P 
sta n dar d o perati n g pr oce d ure 
s- P 
ser u m p h os p h or us 
TI D  
ter i n die, t hree ti mes a da y 
W B C 
w hite bl o o d cell c o u nt 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 2 0 of 6 0 
2  
I N T R O D U C TI O N A N D B A C K G R O U N D 
2. 1  
I ntr o d ucti o n 
C hr o nic ki d ne y disease ( C K D) affects 5- 1 0 % of t he p o p ulati o n gl o ball y a n d t he n u m bers of 
patie nts s ufferi n g fr o m e n d-sta ge re nal disease ( E S R D) are i ncreasi n g ( E k n o ya n 2 0 0 5 ). Wit h 
pr o gressi n g i m pair me nt of re nal f u ncti o n, t he a bilit y of t he ki d ne ys t o a p pr o priatel y e xcrete 
p h os p hate is re d uce d a n d h y per p h os p hate mia is a nearl y u ni versal c o m plicati o n of E S R D. 
H y per p h os p hate mia is als o part of t he C K D b o ne mi neral dis or der, w hic h is ass ociate d wit h a 
disr u pti o n of n or mal ser u m a n d tiss ue c o nce ntrati o ns of p h os p h or us a n d calci u m, a n d 
c ha n ges i n circ ulati n g le vels of h or m o nes s uc h  as parat h yr oi d h or m o ne ( P T H) a n d vita mi n D. 
Left u ntreate d, h y per p h os p hate mia ca n lea d t o vasc ular a n d tiss ue calcificati o ns, b o ne pai n, 
fract ures, a n d w orse ni n g sec o n dar y h y per parat h yroi dis m a n d is ass ociate d wit h i ncrease d 
car di o vasc ular m or bi dit y a n d m ortalit y. O bser vati o nal data s h o w t hat treat me nt wit h 
p h os p hate bi n ders t o re d uce h y per p h os p hate mia is  i n de pe n de ntl y ass ociate d wit h i m pr o ve d 
s ur vi val (Wa hee d 2 0 1 3 ). E x peri me ntal st u dies pr o vi de s u p p ort f or t he e pi de mi ol o gic 
fi n di n gs: p h os p hate e xcess pr o m otes vasc ular calcificati o n, i n d uces e n d ot helial d ysf u ncti o n 
a n d ma y c o ntri b ute t o ot her e mer gi n g C K D-s pecific mec ha nis ms of car di o vasc ular t o xicit y 
(Wa hee d 2 0 1 3 ). He nce, cli nical treat me nt g ui deli nes f or patie nts wit h a d va nce d ki d ne y 
disease s u g gest mai ntai ni n g ser u m p h os p h or us (s- P) wit hi n 3. 5 t o 5. 5 m g/ d L, w hic h is cl ose 
t o t he n or mal ra n ge (K DI G O G ui deli ne 2 0 0 9 ). 
I n a d diti o n t o dietar y p h os p h or us restricti o ns a n d dial ysis, 8 0- 9 0 % of E S R D patie nts nee d 
treat me nt wit h oral p h os p hate bi n ders. Des pite wi des prea d use of p h osp hate bi n ders, a lar ge 
pr o p orti o n of patie nts d o n ot ac hie ve a de q uate p h os p h or us c o ntr ol ( D O P P S Practice M o nit or 
2 0 1 8 ). T he bi n di n g mec ha nis m re q uires fre q ue nt d osi n g a n d ofte n, ma n y la r ge pills i n or der 
t o bi n d e n o u g h dietar y p h os p h or us, a n d te n ds t o be ass ociate d wit h a si g nifica nt n u m ber of 
gastr oi ntesti nal ( GI) si de effects i ncl u di n g bl oati n g, c o nsti pati o n a n d na usea. Effecti vel y 
treate d h y per p h os p hate mia wit h bi n ders is e xtre mel y diffic ult beca use of t he c o nsi dera ble 
b ur de n t hat bi n ders place o n patie nts. I n a d di ti o n t o t he pill b ur de n a n d d osi n g fre q ue nc y 
ass ociate d wit h all p h os p hate bi n ders, t he si de effect pr ofile wit h p o or  GI t olera bilit y a n d 
c o ncer ns f or l o n g-ter m ne gati ve effects s uc h  as tiss ue calcificati o n, a n d p ote ntial metal 
acc u m ulati o n t o xicit y fr o m calci u m- base d a n d metal- base d bi n ders, res pecti vel y, f urt her 
i m pair effecti ve p h os p h or us c o ntr ol i n E S R D patie nts. T here is, t heref ore, a n u n met me dical 
nee d t o de vel o p oral p h os p hate-l o weri n g me dicati o ns wit h ne w mec ha nis ms of acti o n, a 
m ore ma na gea ble d osi n g a n d a d mi nistrati o n re gi me n, a n d i m pr o ve d ris k- be nefit pr ofile. 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 2 1 of 6 0 
Te na pa n or is a n oral, esse ntiall y n o n-a bs or be d, l ocall y acti n g i n hi bit or t hat tar gets t he 
s o di u m/ h y dr o ge n e xc ha n ger 3 ( N H E 3), a n a nti p orter e x presse d o n t he a pical s urface of t he 
e pit heli u m of t he s mall i ntest i ne a n d c ol o n. I n hi biti o n of N H E 3 b y te na pa n or res ults i n 
re d uce d s o di u m a bs or pti o n a n d c o nse q ue ntl y, pr ot o n rete nti o n i n cells. T his m o dest 
i ntracell ular pr ot o n rete nti o n i n d uces a c o nf or mati o nal c ha n ge i n cla u di n pr otei ns prese nt i n 
ti g ht j u ncti o ns, re d uci n g per mea bilit y s pecific t o p h os p hate.  
Te na pa n or re d uces i ntesti nal p h os p hate a bs o r pti o n, pre d o mi na ntl y t hr o u g h re d ucti o n of 
passi ve paracell ular p h os p hate i nfl u x, t he m ost i m p orta nt o verall mec ha nis m of i ntesti nal 
p h os p hate a bs or pti o n. Te na pa n or m o d ulates ti g ht j u ncti o ns t o i ncrease t he tra nse pit helial 
electrical resista nce, t here b y re d uci n g paracell ular p h os p hate per mea bilit y; t his effect is 
me diate d e xcl usi vel y via o n-tar get N H E 3 i n hi biti o n. Bl oc ki n g N H E 3 b y te na pa n or has n o 
o bser ve d effect o n ser u m s o di u m, n or o n t he a bs o r pti o n of i o ns, n utrie nts, or macr o m olec ules 
ot her t ha n dietar y s o di u m a n d p h os p h or us. 
Res ults fr o m t hree P hase 3 st u dies ha ve de m o nstr ate d t he efficac y of te na pa n or i n decreasi n g 
s- P le vels i n a d ult C K D patie nts o n dial ysis wit h h y per p h os p hate mia, as b ot h a m o n ot hera p y 
a n d as a d ual- mec ha nis m a p pr oa c h wit h p h os p h ate bi n ders. 
Te na pa n or (I B S R E L A ® ) has bee n a p pr o ve d f or t he treat me nt of irrita ble b o wel s y n dr o me 
wit h c o nsti pati o n (I B S- C). Te na pa n or has b ee n a d mi nistere d t o gr eater t ha n 2 8 0 0 pe o ple 
i ncl u di n g healt h y v ol u nteers, patie nts wit h I B S- C, C K D wit h Ty pe 2 dia betes mellit us, a n d 
C K D o n dial ysis. Te na pa n or has bee n e val uate d i n s h ort ter m st u dies u p t o 9 0 0 m g/ da y a n d 
f or > 2 0 m o nt hs at 6 0 m g/ da y.   
2. 2  
Descri pti o n of I n vesti g ati o n al Pr o d uct 
Te na pa n or is a GI-acti n g, mi ni mall y s yste mic, N H E 3 i n hi bit or. Te na pa n or is a d mi nistere d as 
t he h y dr oc hl ori de salt a n d is c he micall y descri be d as: ( S)- N, N’-( 1 0, 1 7- di o x o- 3, 6, 2 1, 2 4-
tetra o xa- 9, 1 1, 1 6, 1 8-tetraaza he xac osa ne- 1, 2 6- di yl) bis( 3-(( S)- 6, 8- dic hl or o- 2- met h yl- 1, 2, 3, 4-
tetra h y dr ois o q ui n oli n- 4- yl) be nze nes ulf o na mi de) di h y dr oc hl ori de. Its e m pirical f or m ula is 
C 5 0H 6 8Cl 6N 8O 1 0S 2. 
Te na pa n or ta blets will be s u p plie d as 1 0 m g, 2 0 m g a n d 3 0 m g ta blets. 
 
 
 
 
 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 2 2 of 6 0 
 
 
 
 
 
D osi n g c o nsists of o ne 1 0 m g, 2 0 m g or 3 0 m g ta blet, ta ke n orall y BI D j u st pri or t o brea kfast 
a n d di n ner ( b ut n ot pri or t o t he meal i m me diatel y pri or t o he m o dial ysis).  
Te na pa n or ta blets, 1 0 m g, 2 0 m g a n d 3 0 m g, are pac ka ge d i n a n i n d ucti o n seale d, o pa q ue 
w hite hi g h- de nsit y p ol yet h yle ne ( H D P E) b ottle ( 2 0 ta blets/ b ottle) wit h a w hite p ol y pr o p yle ne 
c hil d resista nt cl os ure a n d a desi cca nt ca nister. Ta blets of te na pa n or s h o ul d be st ore d i n t he 
ori gi nal pac ka gi n g acc or di n g t o t he la beli n g.  
2. 3  
St u d y R ati o n ale 
Te na pa n or is a n i n vesti gati o nal pr o d uct bei n g e val uate d f or its a bilit y t o co ntr ol s- P le vels i n 
a d ult patie nts wit h C K D o n dial ysis. M ost C K D patie nts o n dial ys is c urre ntl y ta ke p h os p hate 
bi n ders t o c o ntr ol s- P le vels. A si g nifica nt pr o p orti o n of E S R D patie nts still d o n ot ac hie ve 
a de q uate p h os p hate c o ntr ol ( D O P P S Practice M o nit or 2 0 1 9 ). Si nce te na pa n or l o wers s- P 
le vels via a differe nt mec ha nism of acti o n, it is belie ve d t hat te na pa n or as m o n ot hera p y or 
c o m bi ne d wit h c urre nt p h os p hate bi n der t hera p y will pr o d uce a d diti o nal p h os p h or us-
l o weri n g acti vit y. T his st u d y is desi g ne d t o i n vesti gate differe nt met h o ds of i nitiati n g 
te na pa n or t hera p y i n C K D patie nts o n dial ysis wit h h y per p h os p hate mia. 
2. 4  
Ris k- Be nefit Assess me nt 
T he ris k- be nefit assess me nt of te na pa n or is base d o n n o ncli nical t o xic ol o g y, safet y, a n d 
p har mac ol o g y st u dies as well as 2 5 cli nical trials c o n d ucte d wit h  te na pa n or. Res ults fr o m t he 
ris k- be nefit assess me nt are descri be d i n t he I n vesti gat or’s Br oc h ure (I B). 
N o ncli nical t o xic ol o gical st u dies of u p t o 9 m o nt hs ha ve bee n c o n d ucte d i n r o de nts a n d d o gs. 
T he t o xic ol o gical pr ofile i ncl u des s oft st o ols a n d/ or diarr h ea a n d fi n di n gs sec o n dar y t o 
de h y drati o n; t hese fi n di n gs are a n e x pecte d ma nifestati o n of t he c o m p o u n d’s e xa g gerate d 
p har mac ol o gic acti vit y a n d fi n di n gs were re versi ble d uri n g t he r ec o ver y peri o d wit h o ut 
me dicati o n. A t w o- year carci n o ge nicit y st u d y i n S pra g ue- D a wle y rats was ne gati ve. 
T he safet y, t olera bilit y, p har mac o d y na mics, a n d e fficac y of te na pa n or ha ve bee n e val uate d i n 
greater t ha n 2 8 0 0 pe o ple i ncl u di n g healt h y v ol u nteers, patie nts wit h I B S- C, C K D wit h 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 2 3 of 6 0 
T y pe 2 dia betes mellit us, a n d C K D o n dial ysis . Te na pa n or has bee n e val uate d i n s h ort-ter m 
st u dies u p t o 9 0 0 m g/ da y a n d f or > 2 0 m o nt hs at 6 0 m g/ da y. 
Te na pa n or has mi ni mal s yste mic bi oa vaila bilit y. Less t ha n 1 % of plas ma p har mac o ki netics 
sa m ples c ollecte d d uri n g h u ma n st u dies ( > 3 0 0 0 sa m ples) ha ve q ua ntifia ble te na pa n or prese nt 
i n bl o o d plas ma (l o wer li mit of q ua ntificati o n = 0. 5 n g/ m L); all sa m ples wit h q ua ntifia ble 
te na pa n or were bel o w 1. 5 n g/ m L.  
T he re d ucti o n i n s o di u m u pta ke res ults i n a n i ncrease i n net fl ui d v ol u me i n t he i ntesti nal 
tract. Base d o n t his mec ha nis m of acti o n, te na pa n or has t he p o te ntial t o pr o d uce s ofter or 
l o oser st o ols a n d i ncrease st o ol fre q ue nc y. Te na pa n or has bee n de m o nstrate d t o be ge nerall y 
safe a n d well t olerate d i n cli nical st u dies. T he safet y pr ofile wit h s o fte ni n g or l o ose ni n g of 
st o ol c o nsiste nc y a n d GI a d verse e ve nts ( A Es) ha ve bee n c o nsiste nt wit h its p har mac ol o g y.  
T he t he oretical A Es fr o m te na pa n or treat me nt i n C K D patie nts o n dial ysis w o ul d be d ue t o 
e xa g gerate d p har mac ol o gical effects a n d ma y i ncl u de electr ol yte dist ur ba nces, meta b olic 
aci d osis, s oft st o ols/ diarr hea, a n d re d uce d bl o o d press ure. W hile a s ofte ni n g or l o ose ni n g of 
t he st o ol wit h a n i ncrease d fl ui d l oss via t he i ntesti ne is a n i nte n de d a n d desire d effect of 
te na pa n or i n s o me patie nts, se nsiti ve patie nts s h o ul d be m o nit ore d f or si g ns of de h y drati o n i n 
case of pr ol o n ge d se vere diarr hea. T his st u d y pr ot oc ol i ncl u des cli nical  la b orat or y tests a n d 
vital si g ns. T he healt h stat us of eac h patie nt wi ll be c hec ke d at eac h visit. All patie nts will 
c o nti n ue t heir e xisti n g treat me nt  wit h p h os p hate bi n ders w he n t heir partici pati o n i n t he st u d y 
e n ds. See t he I B f or details o n n o n-cli nical a n d cli nical res ults wit h te na pa n or. 
Patie nts will be i nf or me d b ot h ver ball y a n d i n writi n g a b o ut t hese as pect s bef ore ta ki n g part 
i n a n y st u d y-s pecific e xa mi nati o n. T he st u d y will be c o n d ucte d u n der c o n diti o ns t hat e ns ure 
a hi g h pr o ba bilit y f or t he earl y detecti o n of u nt o war d e ve nts a n d f or a p pr o priate i nter ve nti o n. 
I n s u m mar y, ris ks t o partici pa nts i n t his sh ort-ter m st u d y are c o nsi dere d acce pta ble. Res ults 
fr o m t his st u d y will be i m p orta nt f or t he p ote ntial use of t his ne w t hera p y, w hic h c o ul d 
i m pr o ve t he treat me nt of h y per p h osp hate mia i n E S R D patie nts. 
3  
S T U D Y O B J E C TI V E S 
3. 1  
Pri m ar y O bjecti ve 
T he pri mar y o bjecti ve of t his st u d y is: 
 T o e val uate t he effect of te na pa n or al o ne or i n c o m bi na ti o n wit h p h os p hate bi n ders t o 
ac hie ve tar get ser u m p h os p h or us (s- P) le vels of ≤5. 5 m g/ d L w he n te na pa n or is 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 2 4 of 6 0 
a d mi nistere d as t he c ore  t hera p y (al o ne or i n c o m bi nati o n wit h p h os p hate bi n der) f or t he 
treat me nt of h y per p h os p hate mia i n patie nts wit h C K D o n dial ysis. 
3. 2  
Sec o n d ar y O bjecti ves 
T he sec o n dar y o bjecti ves of t his st u d y, f or t he treat me nt of h y pe r p h os p hate mia i n C K D 
patie nts o n dial ysis w h o are p h os p hate bi n der naï ve or o n p h os p hate bi n der t hera p y, i ncl u de: 
 T o e val uate t he effect of te na pa n or al o ne or i n c o m bi na ti o n wit h p h os p hate bi n ders t o 
ac hie ve vari o us s- P le vels (e. g., ≤4. 5 m g/ d L). 
 T o e val uate differe nt strate gi es of i nitiati n g te na pa n or f o r t he c o ntr ol of s- P le vel. 
 T o e val uate t he effect of di ffere nt strate gies of i nitiatin g te na pa n or o n st o ol fre q ue nc y 
a n d c o nsiste nc y usi n g a dail y e Diar y. 
 T o e val uate t he effect of te na pa n or o n re d uci n g dail y p h os p h or us-l o weri n g t hera p y pill 
b ur de n ( n u m ber of pills a n d t otal pill wei g ht) w he n patie nts are starte d o n or tra nsiti o ne d 
t o te na pa n or fr o m c urre nt p h os p hate bi n der t hera p y. 
 T o e val uate t he i m pact of patie nt e d ucati o n a n d use of sta n dar d of care me dicati o n o n t he 
t olera bilit y ma na ge me nt of te na pa n or. 
 T o e val uate t he t olera bilit y of te na pa n or w he n patie nts are starte d o n or tra nsiti o ne d t o 
te na pa n or fr o m c urre nt p h os p hate bi n der t hera p y. 
 T o e val uate patie nt e x perie nce wit h p h os p h or us ma na ge me nt r o uti ne d uri n g st u d y 
c o m pare d t o bef ore st u d y. 
 T o e val uate t he effect of te na pa n or al o ne or i n c o m bi nati o n wit h p h os p hate bi n ders o n 
i F G F 2 3 a n d P T H. 
 T o e val uate t he effect of te na pa n or al o ne or i n c o m bi nati o n wit h p h os p hate bi n ders o n 
t he use of P T H- m o dif yi n g me dicati o ns. 
4  
S T U D Y D E SI G N 
4. 1  
Desi g n S u m m ar y 
T his is a ra n d o mize d, o p e n-la bel st u d y t o e val uate differe nt met h o ds of i nitiati n g te na pa n or 
t hera p y i n C K D patie nts o n dial ysis wit h h y per ph os p hate mia, w he n t he y are eit her p h os p hate 
bi n der naï ve or o n p h os p hate bi n der t hera p y. T h e st u d y c o nsists of a Scree ni n g visit, a 
1 0- wee k o pe n-la bel Treat me nt Peri o d ( Par t A), a n d a n o pti o nal 1 6- wee k o pe n-la bel 
E xte nsi o n Peri o d ( Part B), wit h a t otal of t hree c o h orts of patie nts as s h o w n i n Fi g ure 4- 1 : 
 Patie nts wit h s- P > 5. 5 a n d ≤1 0. 0 m g/ d L u n der sta ble p h os p hate bi n der treat me nt 
re gi me n are ra n d o mize d i n a 1: 1 rati o t o t w o differe nt treat me nt c o h orts:  


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 2 5 of 6 0 
o  C o h ort 1 (strai g ht s witc h), w hic h st o ps ta ki n g p h os p hate bi n ders a n d is 
i m me diatel y starte d o n te na pa n or 3 0 m g t wice dail y ( BI D) at Visit 2 ( Da y 1);  
o  C o h ort 2, w hic h decreases p h os p hate bi n der d ose b y at least 5 0 % ( ma y be 
m ore t ha n 5 0 % if patie nt is ta ki n g a n  o d d n u m ber of bi n der pills eac h da y), 
wit h a bilit y t o s witc h t he bi n der re gi me n fr o m t hrice dail y ( TI D) t o BI D or 
Q D; a n d i nitiates te na pa n or 3 0 m g  BI D at Visit 2 ( Da y 1).  
 P h os p hate bi n der naï ve patie nts wit h s- P > 4. 5 a n d ≤1 0. 0 m g/ d L are e nr olle d as 
C o h ort 3 a n d recei ve te na pa n or at Visit 2 ( Da y  1) wit h a starti n g d ose of 3 0 m g BI D. 
Fi g ure 4- 1:  
St u d y Desi g n Di a gr a m 
 
a  Da y 1 is t he ra n d o mizati o n/e nr oll me nt da y a n d ser ves as t he refere nce da y f or all visits.  
 
T he Scree ni n g visit ( Visit 1) m ust be sc he d ule d at t he first s h ort dial ysis i nter val of t he wee k 
( We d nes da y or T h urs da y), t he Ra n d o mizati o n/ E nr oll me nt visit ( V isit 2) m ust be sc he d ule d 
t w o da ys after t he Scree ni n g visit at t he sec o n d sh ort dial ysis i nter val of  t he wee k ( Fri da y or 
Sat ur da y), a n d all ot her visits i n t he st u d y m ust  be sc he d ule d after a s hort dial ysis i nter val 
( We d nes da y or Fri da y f or patie nts o n a M o n da y- We d nes da y- Fri da y sc he d ule a n d T h urs da y 
or Sat ur da y f or patie nts o n a T ues da y- T h urs d a y- Sat ur da y sc he d ule). B o d y wei g ht, vital si g ns, 
a n d bl o o d c ollecti o ns f or la b orat or y assess me nts m ust  be perf or me d pre- dial ysis ( pri or t o 
dial ysis at t he visit). All ot he r assess me nts ma y be perf or me d pre-, d uri n g, or p ost- dial ysis 
b ut s h o ul d be perf or me d at t he sa me ti me at  eac h visit a n d t he sa me da y as dial ysis.  
T he e nr oll me nt criteria o n s- P will be e val uate d base d o n t he s- P meas ure d at t he Scree ni n g 
visit ( Visit 1) al o ne ( C o h ort 3 o nl y: bi n der naï ve) or t o get her  wit h t he m ost rece nt s- P 
meas ure me nt pri or t o t he Scree ni n g visit ( Visit 1):  


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 2 6 of 6 0 
 Patie nts o n p h os p hate bi n der t hera p y m ust recei ve p h os p hate bi n der(s) t hrice dail y, 
a n d b ot h t he s- P le vel assesse d at t he m ost rece nt meas ure me nt pri or t o t he Scree ni n g 
visit ( Visit 1) a n d t he s- P le vel assesse d at  t he Scree ni n g visit ( Visit 1) m ust be > 5. 5 
a n d ≤1 0. 0 m g/ d L t o q ualif y f or ra n d o mizati o n i nt o C o h ort 1 or C o h ort 2 at Visit 2 
( Da y 1).  
 P h os p hate bi n der naï ve patie nts m ust ha ve t he s- P le vel asse sse d at t he Scree ni n g visit 
( Visit 1) > 4. 5 a n d ≤1 0. 0 m g/ d L t o q ualif y f or e nr oll me nt i nt o C o h ort 3 at Visit 2 
( Da y 1). 
Patie nts w h o d o n ot meet t he ra n d o mizati o n/e nr oll me nt criteria o n s- P will be disc o nti n ue d as 
scree n fail ures. Patie nts m ust c o nti n ue t o meet all ot her a p plica b le i ncl usi o n/e xcl usi o n 
criteria at Visit 2 ( Da y 1) i n or der t o be ra n d o mize d i nt o C o h ort  1 or C o h ort 2 or be e nr olle d 
i n C o h ort 3.  
Patie nts will be e d ucate d at Scree ni n g ( Visit 1) a n d Ra n d o mizati o n/ E nr oll me nt ( Visit 2) 
a b o ut te na pa n or, h o w t o ta ke te na pa n or, w hat  t he y ma y e x perie nce o n te na pa n or, me dicati o ns 
t o be disc o nti n ue d bef ore starti n g te na pa n or, a n d h o w best t o ma na ge a p ossi ble i ncrease i n 
b o wel m o ve me nt fre q ue nc y a n d/ or  l o ose st o ol if b ot hers o me (e. g., use of o ver-t he-c o u nter 
a nti- diarr heal), etc. 
I n or der t o assess t he t olera bilit y pr ofile of te na pa n or al o ne or c o m bi ne d wit h p h os p hate 
bi n ders, patie nts will use a dail y e Diar y t o rec or d dail y b o wel ha bits (st o ol fre q ue nc y a n d 
st o ol c o nsiste nc y) t hr o u g h o ut t he 1 0- wee k Treat me nt Peri o d. 
O n Da y 1 ( Visit 2), patie nts will start t o r ecei ve te na pa n or at a d ose of 3 0 m g BI D.  
Te na pa n or will be ta ke n orall y BI D; j ust pr i or t o brea kfast a n d di n ner. Patie nts s h o ul d n ot  
ta ke st u d y dr u g at t he meal i m me diatel y prece din g he m o dial ysis. T he I n vesti gat or ma y titrate 
t he d ose of te na pa n or i n 1 0 m g i ncre me nts d o w n t o a mi ni m u m of 1 0 m g Q D or u p t o a 
ma xi m u m of 3 0 m g BI D at a n y ti me d uri n g t he st u d y base d o n s- P le vels a n d/ or GI 
t olera bilit y.  
If a p h os p hate bi n der is bei n g ta ke n b y a patie nt i n a n y of t he t hree c o h orts, it ca n be d ose d 
starti n g at eit her Q D, BI D or TI D: if ta ke n Q D, it s h o ul d be ta ken wit h t he lar gest meal of t he 
da y; if ta ke n BI D, it s h o ul d be ta ke n wit h t he sa me meals te na pa n or is ta ke n wit h. T he 
I n vesti gat or ma y decrease t he d ose of p h os p hate bi n der at a n y ti me d uri n g t he st u d y base d o n 
s- P le vels. H o we ver, d ose u p-titrati o n f or p h os p hate bi n der is n ot all o we d fr o m Da y 1 ( Visit 
2) u ntil Wee k 2 of t he Treat me nt Peri o d ( Visit 4) . Starti n g fr o m Visit 4, t he I n vesti gat or ma y 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 2 7 of 6 0 
i ncrease t he d ose of p h os p hate bi n der or a d d p h os p hate bi n der base d o n s- P le vels; t he d ose 
of a p h os p hate bi n der ca n be titrate d u p t o t he ma xi m u m d ose TI D per t he c orres p o n di n g 
p h os p hate bi n der pac ka ge i nsert, if nee de d, base d o n s- P le vels.  
If decreasi n g t he d ose of te na pa n or or p h os p hate bi n der d ue t o l o w s- P le vels, t he p h os p hate 
bi n der d ose s h o ul d be decrease d pri or t o decr easi n g t he te na pa n or d ose u ntil patie nt is n o 
l o n ger ta ki n g a n y p h os p hate bi n der. If i ncreasin g t he d ose of te na pa n or or p h os p hate bi n der 
d ue t o hi g h s- P le vels, t he te na pa n or d ose s h o ul d be i ncrease d pri o r t o i ncreasi n g t he 
p h os p hate bi n der d ose u ntil t he te na pa n or d ose re ac hes 3 0 m g BI D or ca n n ot be i ncrease d 
d ue t o GI t olera bilit y at t he I n vesti gat or’s discreti o n. Details of rec o m me n de d d ose 
a dj ust me nts base d o n s- P le vels are pr o vi de d i n Secti o n 6. 1. 4 .    
Safet y assess me nts will be perf or me d at vari o us ti me p oi nts t hr o u g h o ut t he st u d y a n d will 
i ncl u de p h ysical e xa mi nati o n, b o d y wei g ht, vital si g ns, safet y la b orat or y tests, 1 2-lea d 
electr ocar di o gra m ( E C G), a n d A E rec or di n g. St o ol fre q ue nc y a n d st o ol c o nsiste nc y will be 
c ollecte d usi n g a dail y e Diar y  t hr o u g h o ut t he 1 0- wee k Treat me nt Peri o d ( Part A o nl y) as 
t olera bilit y meas ures.    
Bl o o d sa m ples will be c ollecte d t o meas ure s- P, i F G F 2 3, P T H, a n d cli nical la b orat or y 
c he mistr y a n d he mat ol o g y tests; a d diti o nal sa m ples will be st ore d, as a p pr o priate, f or t he 
p ote ntial e val uati o n of e x pl orat or y bi o mar kers. 
A p pr o xi matel y 3 0 0 C K D patie nts o n dial ysis a n d sta ble p h os p hate bi n der t hera p y will be 
ra n d o mize d i n a 1: 1 rati o t o C o h ort 1 or C o h ort 2 ( ~ 1 5 0 patie n ts/c o h ort); a n d a p pr o xi matel y 
3 0 p h os p hate bi n der naï ve patie nts wit h C K D o n  dial ysis will be e nr olle d i nt o C o h ort 3. 
O verall, a p pr o xi matel y 3 3 0 patie nts will be ra n d o mize d or e nr olle d at a p pr o xi matel y 4 0 sites 
i n t he U nite d States.  
4. 1. 1  
D ur ati o n of St u d y 
T he treat me nt d urati o n of t his  st u d y will be u p t o 2 6 wee ks i ncl u di n g a 1 0- wee k Treat me nt 
Peri o d ( Part A) a n d a n o pti o nal 1 6- wee k E xte nsi o n Peri o d ( Part B).  
5  
S E L E C TI O N A N D WI T H D R A W A L O F P A TI E N T S 
5. 1  
I ncl usi o n Criteri a 
A patie nt will be eli gi ble f or st u d y partici pa ti o n if he/s he meets t he f oll o wi n g criteria: 
1.  
Si g ne d a n d date d i nf or me d c o nse nt f or m (I C F)  pri or t o a n y st u d y s pecific pr oce d ures. 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 2 8 of 6 0 
2.  
Males or fe males a ge d 1 8 t o 8 0 years, i ncl usi ve, at Scree ni n g ( Visit 1). 
3.  
Fe males m ust be n o n- pre g na nt a n d n o n-lactati n g. 
4.  
Patie nts o n p h os p hate bi n der t hera p y m ust be  o n c hr o nic mai nte na nce he m o dial ysis 
( H D) 3 ti mes per wee k f or at least 3 m o nt hs or c hr o nic mai nte na nce perit o neal dial ysis 
( P D) f or a mi ni m u m of 6 m o nt hs. If m o dalit y of dial ysis has c ha n ge d, t he patie nt m ust 
meet o ne of t he t w o dial ysis criteria a b o ve a n d bee n o n t he ne w m o dalit y of dial ysis f or 
a mi ni m u m of o ne m o nt h. P h os p hate bi n der naï ve patie nts m u st be o n c hr o nic 
mai nte na nce H D 3 ti mes per wee k or c hr o nic mai nte na nce P D.  
5.  
Kt/ V ≥1. 2 at m ost rece nt meas ure me nt pri or t o Scree ni n g ( Visit 1). 
6.  
Prescri be d a n d ta ki n g p h os p hate bi n der me di cati o n at least 3 ti me s per da y or bei n g 
p h os p hate bi n der naï ve; defi ne d as ha vi n g n ot ta ke n p h os p ha te bi n ders f or at least 
3 m o nt hs pri or t o Scree ni n g. T he patie nt m u st be ta ki n g a mi ni m u m of 6 pills per da y 
f or Re n vela, A ur y xia, or P h os L o; a n d/ or a mi ni m u m of 3 pills per da y f or F osre n ol or 
Vel p h or o. 
7.  
F or patie nts ta ki n g p h os p hate bi n ders, b ot h t he s- P at t h e m ost rece nt meas ure me nt 
pri or t o Scree ni n g ( Visit 1) a n d t he s- P le vel at Scree ni n g ( Visit 1) m ust be > 5. 5 a n d 
1 0. 0 m g/ d L.  
8.  
F or p h os p hate bi n der naï ve patie nts, t he s- P le vel at Scree ni n g ( Visit 1) m ust be > 4. 5 
a n d ≤1 0. 0 m g/ d L.  
9.  
A ble t o u n dersta n d a n d c o m pl y wit h t he pr ot oc ol. 
5. 2  
E xcl usi o n Criteri a 
A patie nt will n ot be eli gi ble f or st u d y partici pati o n if he/s he meets a n y of t he f oll o wi n g 
e xcl usi o n criteria, or will be disc o nti n ue d at t he discreti o n of  t he I n vesti gat or if he/s he 
de vel o ps a n y of t he f oll o wi n g me dical c o n diti o ns d uri n g t he st u d y: 
1.  
Se vere h y per p h os p hate mia defi ne d as ha vi n g a n s- P le vel > 1 0. 0 m g/ d L at a n y ti me 
p oi nt d uri n g r o uti ne cli nical m o nit ori n g f o r t he 3 prece di n g m o nt hs bef ore Scree ni n g 
( Visit 1). 
2.  
Ser u m/ plas ma P T H > 1 2 0 0 p g/ m L. T he m ost re ce nt val ue fr o m t he patie nt’s me dical 
rec or ds s h o ul d be use d. 
3.  
Cli nical si g ns of h y p o v ole mia at Scree ni n g ( Visit 1) as j u d ge d b y t he I n vesti gat or. 
4.  
Hist or y of i nfla m mat or y b o wel disease or irrita ble b o wel s y n dr o me wit h diarr hea. 
5.  
Sc he d ule d f or li vi n g d o n or ki d ne y tra ns pla nt  or pla ns t o rel ocate t o a n ot her ce nter 
d uri n g t he st u d y. 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 2 9 of 6 0 
6.  
Use of a n i n vesti gati o nal a ge nt wit hi n 3 0 da ys pri or t o Scree ni n g ( Visit 1). 
7.  
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 
Ar del y x/ C o ntract Researc h Or ga nizati o n ( C R O) staff a n d/ or staff at t he st u d y site).  
8.  
If, i n t he o pi ni o n of t he I n vesti gat or, t he patie nt is u na ble or u n willi n g t o f ulfill t he 
re q uire me nts of t he pr ot oc ol or has a c o n diti o n w hic h w o ul d re n der t he res ults 
u ni nter preta ble.  
5. 3  
P atie nt Wit h dr a w al 
Patie nts are free t o disc o nti n ue t he st u d y at a n y ti me, f or a n y reas o n, a n d wit h o ut prej u dice t o 
f urt her treat me nt. T he I n vesti gator ma y re m o ve a patie nt if, i n  t he I n vesti gat or’s j u d g me nt, 
c o nti n ue d partici pati o n w o ul d p ose u nacce pta ble ris k  t o t he patie nt or t o t he i nte grit y of t he 
st u d y data. If p ossi ble, all assess me nts a n d pr oce d ures sc he d ule d f or Visit 9 e xce pt st u d y 
dr u g dis pe nsi n g will be c o m plete d at t he Earl y Ter mi nati o n visit f or patie nts w h o 
pre mat urel y disc o nti n ue fr o m t he st u d y bef ore Visit 9; t h ose sc he d ule d f or Visit 1 3 will be 
c o m plete d at t he Earl y Ter mi nati o n visit f or patie nts w h o pre mat urel y disc o nti n ue fr o m t he 
st u d y bet wee n Visit 9 a n d Visit 1 3 (Secti o n 8. 9  a n d Secti o n 8. 1 0 ).  
5. 4  
E arl y Ter mi n ati o n of St u d y 
T he st u d y ma y be ter mi nate d at a n y ti me b y t he S p o ns or if seri o us si de eff ects occ ur, or if, i n 
t he S p o ns or’s j u d g me nt, t here are n o f urt her be nefits t o be ac hie ve d fr o m t he st u d y, or f or 
a d mi nistrati ve reas o ns. A site ma y be cl ose d if t he I n vesti gat or d oes n ot a d here t o t he 
pr ot oc ol or G o o d Cli nical Practic e ( G C P). I n t he e ve nt t hat t h e cli nical de vel o p me nt of t he 
i n vesti gati o nal pr o d uct is disc o nti n ue d, t he S p o ns or s hall i nf or m all I n vesti gat ors/i nstit uti o ns 
a n d t he I nstit uti o nal Re vie w B o ar d (I R B) o verseei n g t he trial. 
6  
T R E A T M E N T O F P A TI E N T S 
6. 1  
A d mi nistr ati o n of I n vesti g ati o n al Pr o d uct 
6. 1. 1  
I de ntit y of I n vesti g ati o n al Pr o d uct(s) 
Te na pa n or h y dr oc hl ori de is a n a m or p h o us, off- w hite t o w hite p o w der. Te na pa n or ta blets will 
be s u p plie d as yell o w ( 1 0 m g), br o w n ( 2 0 m g), re d ( 3 0 m g), o val, bic o n ve x ta blets pac ka ge d 
i n H D P E b ottles wit h a desicca nt ca nister. Eac h b ottle c o ntai ns t we nt y ( 2 0) ta blets.  
T he 1 0 m g ta blets c o ntai n 1 0. 6 m g of t he te na pa n or h y dr oc hl ori de salt, t he 2 0 m g ta blets 
c o ntai n 2 1. 3 m g of t he te na pa n or  h y dr oc hl ori de salt, a n d t he 3 0 m g ta blets c o ntai n 3 1. 9 m g 
of t he te na pa n or h y dr oc hl ori de salt. T he 1 0 m g, 2 0 m g a n d 3 0 m g ta blets are o val bic o n ve x 
fil m-c oate d ta blets wit h t he f oll o wi n g e xci pie nts: stearic aci d, h y dr o x y pr o p ylcell ul ose, 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 3 0 of 6 0 
micr ocr ystalli ne cell ul ose, silic o n di o xi de, tartaric aci d, pr o p yl gallate, h y pr o mell ose, 
triaceti n, tita ni u m di o xi de a n d a c ol ora nt as descri be d bel o w.   
T he 1 0 m g ta blets c o ntai n yell o w ir o n o xi de as  t he c ol ora nt a n d are yell o w i n c ol or, t he 
2 0 m g ta blets c o ntai n yell o w a n d re d ir o n o xi de as t he c ol ora nts a n d are br o w n i n c ol or a n d 
t he 3 0 m g ta blets als o c o ntai n red a n d blac k ir o n o xi de as t he c o l ora nts a n d are re d i n c ol or. 
6. 1. 2  
I de ntit y of P h os p h ate Bi n ders 
A n y p h os p hate bi n der t hat is a p pr o ve d f or use f or t he c o ntr o l of h y per p h os p hate mia i n t he 
U nite d States ca n be a d mi nistere d t o patie nts i n t his st u d y. 
All patie nts i n C o h orts 1 a n d 2 t hat nee d t o ta ke p h os p hate bi n ders as part of t his pr ot oc ol 
will ta ke t he p h os p hate bi n der t hat t he y were pr escri be d pri or t o e nr olli n g i n t his st u d y. F or 
t h ose i n C o h ort 3 w h o nee d t o ta ke p h os p hate bi n der as part of t his pr ot oc ol, t he c h oice of 
bi n der is u p t o t he I n vesti gat or. 
6. 1. 3  
Tre at me nts A d mi nistere d 
All patie nts ta ki n g a p h os p hate bi n der will ta ke  t he sa me p h os p hate bi n der t hat t he y t o o k 
pri or t o e nr olli n g i n t he st u d y. D u ri n g t he st u d y, p h os p hate bi n der ca n be d ose d starti n g at 
eit her Q D, BI D or TI D: if ta ke n Q D, it s h o ul d be ta ke n wit h t he lar gest meal of t he da y; if 
ta ke n BI D, it s h o ul d be ta ke n wit h t he sa me meals te na pa n or is ta ke n wit h. T he d ose of a 
p h os p hate bi n der ca n be titrate d u p t o t h e ma xi m u m d ose TI D per t he c orres p o n di n g 
p h os p hate bi n der pac ka ge i nsert, if nee de d, base d o n s- P le vels. 
All patie nts will i nitiate te na pa n or t hera p y at a d ose of 3 0 m g BI D. Te na pa n or ta blets will be 
ta ke n orall y BI D, j ust pri or t o brea kfast a n d di n ner. O n dial ysis da ys, patie nts o n H D s h o ul d 
n ot ta ke te na pa n or at t he meal i m me diatel y pri or t o dial ysis a n d s h o ul d i nstea d ta ke it j ust 
pri or t o a n ot her meal. If a meal  is s ki p pe d, t he d ose s h o ul d be ta ke n wit h a n ot her meal d uri n g 
t he da y or at ar o u n d t he ti me t hat t he meal w o ul d ha ve bee n c o ns u me d. 
6. 1. 4  
D ose A dj ust me nts 
T he I n vesti gat or ma y titrate t h e d ose of te na pa n or i n 1 0 m g i n cre me nts d o w n t o a mi ni m u m 
of 1 0 m g Q D or u p t o a ma xi m u m of 3 0 m g BI D at a n y ti me d uri n g t he st u d y base d o n s- P 
le vels a n d/ or GI t olera bilit y.  
If a p h os p hate bi n der is bei n g ta ke n b y a patie nt i n a n y of t he t hree c o h orts, it ca n be d ose d 
starti n g at eit her Q D, BI D or TI D: if ta ke n Q D, it s h o ul d be ta ken wit h t he lar gest meal of t he 
da y; if ta ke n BI D, it s h o ul d be ta ke n wit h t he sa me meals te na pa n or is ta ke n wit h. T he 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 3 1 of 6 0 
I n vesti gat or ma y decrease t he d ose of p h os p hate bi n der at a n y ti me d uri n g t he st u d y base d o n 
s- P le vels. H o we ver, d ose u p-titrati o n f or p h os p hate bi n der is n ot all o we d fr o m Da y 1 
( Visit 2) u ntil Wee k 2 of t he Treat me nt Peri o d ( Visit 4). Starti n g fr o m Visit 4, t he 
I n vesti gat or ma y i ncrease t he d ose of p h os p hate bi n der or a d d p h os p hate bi n der base d o n s- P 
le vels; t he d ose of a p h os p hate bi n der ca n be titrate d u p t o t he ma xi m u m d ose TI D per t he 
c orres p o n di n g p h os p hate bi n der pac ka ge i nse rt, if nee de d, base d o n s- P le vels.  
If decreasi n g t he d ose of te na pa n or or p h os p hate bi n der d ue t o l o w s- P le vels, t he p h os p hate 
bi n der d ose s h o ul d be decrease d pri or t o decr easi n g t he te na pa n or d ose u ntil patie nt is n o 
l o n ger ta ki n g a n y p h os p hate bi n der. If i ncreasin g t he d ose of te na pa n or or p h os p hate bi n der 
d ue t o hi g h s- P le vels, t he te na pa n or d ose s h o ul d be i ncrease d pri o r t o i ncreasi n g t he 
p h os p hate bi n der d ose u ntil t he te na pa n or d ose re ac hes 3 0 m g BI D or ca n n ot be i ncrease d 
d ue t o GI t olera bilit y at t he I n vesti gat or’s discreti o n. 
Rec o m me n de d d ose a dj ust me nts base d o n s- P le vels d uri n g t he st u d y are s pecifie d bel o w f or 
eac h c o h ort: 
I n C o h ort 1 (strai g ht s witc h t o te na pa n or),  
 If t he patie nt’s s- P assesse d at or after Visit 4 ( Wee k 2) is > 5. 5 m g/ d L, t he 
I n vesti gat or ma y a d d o ne p h os p hate bi n der pill dail y ( Q D) ( wit h lar gest meal) or o ne 
p h os p hate bi n der pill BI D (at sa me meals as  te na pa n or). T he p h os p hate bi n der d osi n g 
re gi me n s h o ul d start at Q D or BI D; a n d t he d ose of p h os p hate bi n der ca n be titrate d 
u p t o t he ma xi m u m d ose TI D per t he c orre s p o n di n g p h os p hate bi n der pac ka ge i nsert, 
if nee de d. W he n p h os p hate bi n der is bei n g a d de d t o C o h ort 1, t he I n vesti gat or s h o ul d 
use t he p h os p hate bi n der t he patie nt st o p pe d at t he be gin ni n g of t he st u d y. 
 If t he patie nt is ta ki n g p h os p hate bi n der a n d his/ her s- P is < 5. 0 m g/ d L, t he 
I n vesti gat or ma y re m o ve o ne or t w o p h os p hate bi n der pills fr o m t he patie nt’s dail y 
re gi me n. 
 If t he patie nt is ta ki n g n o p h os p hate bi n der a n d his/ her s- P is ≤3. 5 m g/ d L, t he d ose of 
te na pa n or s h o ul d be decrease d b y 1 0 m g BI D. If t he patie nt is ta ki n g te na pa n or 1 0 m g 
BI D, t he n t he d ose of te na pa n or s h o ul d be decrease d t o 1 0 m g Q D. 
I n C o h ort 2 ( 5 0 % p h os p hate bi n der re d ucti o n),  


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 3 2 of 6 0 
 T he re d uce d p h os p hate bi n der d ose ca n be d os e d starti n g at Q D, BI D or TI D wit h 
meals: if ta ke n Q D, it s h o ul d be ta ke n wit h t h e lar gest meal of t he da y; if ta ke n BI D, 
it s h o ul d be ta ke n wit h t he sa me meals te na pa n or is ta ke n wit h. 
 If t he patie nt’s s- P is > 5. 5 m g/ d L, t he In vesti gat or ma y a d d o ne  p h os p hate bi n der pill 
Q D ( wit h lar gest meal) or o ne p h os p hate bi n d er pill BI D (at sa me ti me as te na pa n or). 
T he d ose of p h os p hate bi n der ca n be titra te d u p t o t he ma xi m um d ose TI D per t he 
c orres p o n di n g p h os p hate bi n der pa c ka ge i nsert, if nee de d.  
 If t he patie nt’s s- P is < 5. 0 m g/ d L, t he I n vesti gat or ma y re m o ve o ne or t w o p h os p hate 
bi n der pills fr o m t he pa tie nt’s dail y re gi me n. 
 If t he patie nt is ta ki n g n o p h os p hate bi n der a n d his/ her s- P is ≤3. 5 m g/ d L, t he d ose of 
te na pa n or s h o ul d be decrease d b y 1 0 m g BI D. If t he patie nt is ta ki n g te na pa n or 1 0 m g 
BI D, t he n t he d ose of te na pa n or s h o ul d be decrease d t o 1 0 m g Q D. 
I n C o h ort 3 ( p h os p hate bi n der naï ve),  
 If t he patie nt’s s- P assesse d at or after Visit 4 ( Wee k 2) is > 5. 5 m g/ d L, t he 
I n vesti gat or ma y a d d o ne p h os p hate bi n der pill Q D ( wit h lar gest meal) or o ne 
p h os p hate bi n der pill BI D (at sa me meal as  te na pa n or). T he p h os p hate bi n der d osi n g 
re gi me n s h o ul d start at Q D or BI D; a n d t he d ose of p h os p hate bi n der ca n be titrate d 
u p t o t he ma xi m u m d ose TI D per t he c orre s p o n di n g p h os p hate bi n der pac ka ge i nsert, 
if nee de d. T he I n vesti gat or ca n ch o ose a n y bra n d of p h os p hate bi n der. 
 If t he patie nt is ta ki n g p h os p hate bi n der after Visit 4 ( Wee k 2) a n d his/ her s- P 
assesse d after t he bi n der use is < 5. 0 m g/ d L, t he I n vesti gat or ma y re m o ve o ne or m ore 
p h os p hate bi n der pills fr o m t he patie nt’s re gi me n. 
 If t he patie nt is ta ki n g n o p h os p hate bi n der a n d his/ her s- P ≤3. 5 m g/ d L, t he d ose of 
te na pa n or s h o ul d be decrease d b y 1 0 m g BI D. If t he patie nt is ta ki n g te na pa n or 1 0 m g 
BI D, t he n t he d ose s h o ul d be decrease d t o 1 0 m g Q D. 
6. 1. 5  
Met h o d of Assi g ni n g P atie nts t o Tre at me nt Gr o u ps 
After gi vi n g i nf or me d c o nse nt, patie nts will be all ocate d se q ue ntial e nr oll me nt n u m bers at 
Scree ni n g ( Visit 1). 
S pecificall y f or patie nts o n p h os p hate bi n der t her a p y, a stratifie d ra n d o mizati o n sc he me will 
be e m pl o ye d, wit h t y pe of p h os p hate bi n der (se vela mer, calci u m- base d bi n der, ir o n- base d 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 3 3 of 6 0 
bi n der, ot her n o n-se vela mer bi n der, or a c o m bi nati o n of bi n ders of differe nt t y pes) a n d s- P 
le vel at Visit 1 ( < 7. 5 m g/ d L or ≥7. 5 m g/ d L) as t w o stratifica ti o n fact ors. T he C R O or 
desi g nate d i n de pe n de nt statisticia n will pre par e t he ra n d o mizati o n sc he me i n acc or da nce wit h 
t he C R O’s sta n dar d o perati n g pr oce d ures ( S O Ps) a n d t he ra n d o mizatio n pla n, w hic h reflect 
G C P sta n dar ds. After meeti n g all of t he i ncl us i o n/e xcl usi o n criteria, eli gi ble patie nts o n 
p h os p hate bi n der t hera p y will be ra n d o mize d i n a 1: 1 rati o at Visit 2 ( Da y 1) t o C o h ort 1 or 
C o h ort 2.  
T he ra n d o mizati o n of t his st u d y will be i m ple me nte d via a n I nteracti ve Res p o nse Tec h n ol o g y 
(I R T). T he I R T will all ocate t he c o h ort a n d pr o vi de t he ra n d o mizati o n n u m ber. T he I R T will 
pr o vi de t he a p pr o priate n u m ber of b ottles of te na pa n or.  
If a patie nt wit h dra ws fr o m t he st u d y, his/ her e nr oll me nt a nd ra n d o mizati o n n u m bers ca n n ot 
be re use d. 
6. 2  
I n vesti g ati o n al Pr o d uct St or a ge a n d Acc o u nt a bilit y 
6. 2. 1  
St or a ge C o n diti o ns 
T he I n vesti gat or will e ns ure t hat all st u d y dr u g is st ore d a n d dis pe nse d i n acc or da nce wit h t he 
la bel a n d F o o d a n d Dr u g A d mi nistrati o n ( F D A) re g ulati o ns c o ncerni n g t he st ora ge a n d 
a d mi nistrati o n of i n vesti gati o nal dr u gs. 
Ta blets of te na pa n or s h o ul d be st ore d i n t he ori gi nal pac ka gi n g acc or di n g t o t he b ottle la bel. 
6. 2. 2  
Dr u g Acc o u nt a bilit y 
T he I n vesti gat or m ust e ns ure t hat all dr u g s u p plies are ke pt i n a sec ure l oc ke d area wit h 
access li mite d t o t h ose a ut h orize d b y t he I n vesti gat or. T he I n vesti gat or or t he I n vesti gat or’s 
desi g nee m ust mai ntai n  acc urate rec or ds of t he recei pt of all st u d y dr u g s hi p pe d b y t he 
S p o ns or or t heir re prese ntati ve, i ncl u di n g b ut n ot li mite d t o, l ot n u m ber, e x pirati o n date, 
a m o u nt recei ve d, a n d t he dis p ositi o n of all st u d y dr u g. C urre nt dis pe nsi n g rec or ds will als o 
be mai ntai ne d i ncl u di n g t he date a n d a m o u nt of st u d y dr u g dis pe nse d a n d t he patie nt 
recei vi n g st u d y dr u g. All re mai nin g st u d y dr u g n ot re q uire d b y re g ulati o ns t o be hel d b y t he 
cli nical facilit y m ust be ret ur n e d t o t he S p o ns or or t heir re pr ese ntati ve i m me diatel y after t he 
st u d y c o m pleti o n. 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 3 4 of 6 0 
6. 3  
P ac k a gi n g a n d L a beli n g 
6. 3. 1  
St u d y Dr u g 
Te na pa n or ta blets will be s u p plie d as yell o w ( 1 0 m g),  br o w n ( 2 0 m g), re d ( 3 0 m g), o val, 
bic o n ve x ta blets pac ka ge d i n H D P E b ottles wit h a desicca nt ca nister. Eac h b ottle c o ntai ns 
t we nt y ( 2 0) ta blets.  
Te na pa n or ta blets s h o ul d be st ore d i n t he ori g i nal pac ka gi n g acc ordi n g t o  t he b ottle la bel. 
6. 3. 2  
Bli n di n g Met h o ds 
T his is a n o pe n-la bel st u d y. 
6. 4  
Pri or a n d C o nc o mit a nt T her a p y 
All pri or a n d c o nc o mita nt me dicati o ns ( prescri pti o n a n d o ve r-t he-c o u nter), vita mi n a n d 
mi neral s u p ple me nts, a n d her bs ta ke n  b y t he patie nt i n t he past 3 0 da ys will be  rec or de d i n 
t he Pri or/ C o nc o mita nt Me dicati o ns electr o nic case re por t f or m (e C R F) a n d will i ncl u de start 
a n d e n d dates, d ose a n d r o ute of a d mi nistrati o n, fre q ue nc y, a n d i n dicati o n. Me dicati o ns ta k e n 
f or a pr oce d ure s h o ul d als o be i ncl u de d. 
T o  miti gate t he i m pact of p ossi ble GI si de ef fects wit h te na pa n or, n o n-st u d y me dicati o ns t hat 
ma y  i ncrease b o wel m o ve me nt fre q ue nc y a n d/ or l o ose n st o ol m ust be disc o nti n ue d bef ore 
starti n g te na pa n or a n d pr o hi bite d d uri n g t he st u dy.  At eac h visit, patie nts will be q uesti one d  
w het her t he y are recei vi n g a n y of t hese me dicati o ns; if t he a ns wer  is yes,  patie n ts will be 
i nstr ucte d t o st o p t hese me dicati o ns.  
F or patie nts e x perie nci n g  a n i ncrease i n b o wel m o ve me nt fre q ue nc y a n d/ or l o oser st o ol after 
recei vi n g te na pa n or, n o n-st u d y me dicati o ns s uc h as o ver-t he-co u nter a nti- diarr heal ma y be 
rec o m me n de d f or ma na gi n g t hese GI si de effects.  
T h e use of P T H- m o dif yi n g me dicati o ns d uri n g t he st u d y will be c hec ke d at e ver y visit. A n y 
n e w P T H- m o dif yi n g me dicati o n  use or c ha n ges t o e xisti n g  P T H- m o dif yi n g me dicati o n use 
nee d t o be a de q uatel y rec or de d i n t he Pri or/ C o nc o mita nt Me dicati o ns e C R F. 
T h e c o m plete lists of pr o hi bite d me dicati o ns a n d rec o m me n de d me dicati o ns f or ma na gi n g GI 
si de effects of te na pa n or as well as t he list of c o m m o n P T H- m o dif yin g me dicati o ns ca n be 
f o u n d i n A p pe n di x I . 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 3 5 of 6 0 
7  
C O L L E C TI O N O F S T U D Y V A RI A B L E S 
7. 1  
Rec or di n g of D at a 
T he I n vesti gat or will e ns ure t hat data c ollecte d d uri n g t his st u d y are rec or de d i n t he 
electr o nic data ca pt ure ( E D C) s yste m i n t h e c orres p o n di n g e C R Fs. T he I n vesti gat or will 
e ns ure acc urac y, c o m plete ness, a n d ti meli ness of  t he data rec or de d an d of t he pr o visi o n of 
a ns wers t o data q ueries.  C o m plete d e C R Fs m ust be si g ne d b y t he I n vesti gat or a n d c o pies of 
t he c o m plete d e C R Fs will be arc hi ve d.  
7. 2  
D at a C ollecti o n Pri or t o E nr oll me nt 
At Scree ni n g ( Visit 1), t he f oll o wi n g i nf or mati o n will be c ollecte d fr o m e ver y patie nt t o 
assess t he patie nt’s eli gi bilit y f or f urt her assess me nts: 

Assess me nt of disease stat us o utli ne d  i n t he i ncl usi o n/e xcl usi o n criteria

Date of birt h, se x, race, et h nicit y

Wei g ht ( pre- dial ysis) a n d hei g ht  ( k g a n d c m, res pecti vel y)

Kt/ V – m ost rece nt val ue pri or t o Scree ni n g

Me dical a n d s ur gical hist or y

P h os p hate bi n der c urre ntl y use d a n d prescri be d dail y dose ( m u st be t hree ti mes a da y)

P h ysical e xa mi nati o n

Vital si g ns ( pre- dial ysis)

Electr ocar di o g ra m e val uati o n

Bl o o d sa m ples f or s- P, i F G F 2 3, P T H, cli nical la b orat or y c he mistr y a n d he mat ol o g y tests, 
a nd b i omar ker a nal ys is ( pre- dial ysis)

F S H a n d pre g na nc y te st, if a p plica ble

e Diar y (i nstr ucti o ns a n d be gi n ni n g of data e ntr y f or st o ol fre q ue nc y a n d c o nsiste nc y)

Pri or/c o nc o mita nt me dicati o ns; s pecial atte n ti o n s h o ul d be gi ve n t o me dicati o ns t o be  
d isc onti n ue d bef ore starti n g te na pa n or (see A p pe n di x I ). A n y use of P T H- m o dif yi n g 
me d icati o ns i n t he past 3 0 da ys nee d t o be a de q uatel y rec or de d i n t he Pri o r/ C o nc o mita nt 
Me dicati o ns e C R F.

Patie nt e d ucati o n o n i nf or mati o n a b o ut te na pa n or , h o w t o ta ke te na pa n or, w hat t he y ma y 
e x perie nce o n te na pa n or, me dicati o ns t o be disc o nti n ue d bef ore starti n g te na pa n or, a n d 
h o w best t o ma na ge a p ossi ble i ncrease i n  b o wel m o ve me nt fre q u e ncy a n d/ or l o ose st o ol  
if b ot hers o me (e. g., use of o ver-t he-c o u nter a n ti- diarr heal), etc


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 3 6 of 6 0 
7. 3  
T oler a bilit y a n d S afet y Me as ures 
St o ol fre q ue nc y a n d st o ol c o nsiste nc y will be c ollecte d usi n g a dail y e Diar y t hr o u g h o ut t he 
1 0- wee k Treat me nt Peri o d ( Part A o nl y) as t ole ra bilit y meas ures. Safet y assess me nts will be 
perf or me d d uri n g t he st u d y a n d will i ncl u de p h ysical e xa mi nati o n, b o d y wei g ht, vital si g ns, 
1 2-lea d E C G, safet y la b orat or y tests, a n d A E rec or di n g. B o d y wei g ht, vital si g ns, a n d bl o o d 
c ollecti o ns f or la b orat or y assess me nts m ust  be perf or me d pre- dial ysis ( pri or t o dial ysis at t he 
visit). All ot her assess me nts ma y be perf or me d pre-, d uri n g, or p ost- dial ysis b ut s h o ul d be 
perf or me d at t he sa me ti me at eac h vi sit a n d t he sa me da y wit h dial ysis.  
7. 3. 1  
St o ol Fre q ue nc y a n d C o nsiste nc y 
Patie nts will use a n e Diar y (a n electr o nic de vi ce a p plicati o n) e ver y da y bet wee n 5: 0 0 P M a n d 
1 1: 5 9 P M (l ocal ti me) fr o m Scree ni n g ( Visit 1) t hr o u g h t he e n d of Part A ( Visit 9/ Earl y 
Ter mi nati o n). 
Patie nts will a ns wer q uesti o ns via e Diar y a b o ut  t he n u m ber of b o wel m o ve me nts t he y ha ve 
eac h da y a n d t he st o ol c o nsiste nc y f or eac h b o wel m o ve me nt assesse d b y t he Brist ol St o ol 
F or m Scale s h o w n i n Fi g ure 7- 1 . 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 3 7 of 6 0 
Fi g ure 7- 1:  
Brist ol St o ol F or m Sc ale ( Le wis 1 9 9 7 ) 
 
7. 3. 2  
P h ysic al E x a mi n ati o n 
T he p h ysical e xa mi nati o n will be perf or me d at Scree ni n g ( Visit 1), Visit 9/ Earl y Ter mi nati o n 
(e n d of Part A), a n d Visit 1 3/ Earl y Ter mi nati o n (e n d of Part B) a n d will i ncl u de a n 
assess me nt of t he f oll o wi n g ite ms : ge neral a p peara nce, s ki n (incl u di n g a n y pitti n g e de ma i n 
l o wer le gs or feet), car di o vasc ular, res pirat or y, a b d o me n, l y m p h n o des, m usc ul os keletal, a n d 
ne ur ol o gical s yste ms. A n y fi n di n gs  or a bse nce of fi n di n gs relative t o eac h patie nt’s p h ysical 
e xa mi nati o n will be caref ull y d oc u me nte d i n t he e C R F. 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 3 8 of 6 0 
7. 3. 3  
B o d y Wei g ht a n d Vit al Si g ns ( bl o o d press ure a n d he art r ate) 
B o d y wei g ht, bl o o d press ure a n d heart rate will be o btai ne d pre- dial ysis at Scree ni n g 
( Visit 1), Visit 9/ Earl y Ter mi nati o n (e n d of Part A), a n d Visit 1 3/ Earl y Ter mi nati o n (e n d of 
Part B). S yst olic a n d diast olic bl o o d press ure w ill be meas ure d after t he patie nt has bee n i n 
sitti n g or s u pi ne p ositi o n f or at least 5 mi n utes. All meas ure m e nts will be rec or de d o n t he 
s o urce d oc u me nt a n d i n t he e C R F. 
7. 3. 4  
Electr oc ar di o gr a m 
A 1 2-lea d E C G will be perf or me d at Scree ni n g ( Visit 1), Visit 9/ Earl y Ter mi nati o n (e n d of 
Part A), a n d Visit 1 3/ Earl y Ter mi nati o n (e n d of Pa rt B) after t he patie nt has bee n i n a sitti n g 
or s u pi ne p ositi o n f o r at least 5 mi n utes. 
T he f oll o wi n g E C G para meters will be rec or d e d: heart rate, P R-i nter val, Q R S- d urati o n, 
Q T-i nter val ( u nc orrecte d), Q Tc-i nter val (c o rrecte d), R R-i nter val, an d t he I n vesti gat or’s 
i nter pretati o n o n t he E C G pr ofile.  
T he I n vesti gat or will assess w het her t he E C G is n or mal or a b n or mal; a b n or malities will be 
f urt her classifie d as cli nicall y si g nifica nt a n d n ot cli nicall y si g nifica nt. Electr ocar di o gra p hic 
i nter vals a n d t he I n vesti gat or’s assess me nt of all a b n or mal E C Gs will be rec or de d i n t he 
e C R F. 
A d diti o nal E C Gs ma y be o btai ne d if cli nicall y i n dicate d a n d rec or de d as a n u nsc he d ule d 
visit.  
7. 3. 5  
Cli nic al L a b or at or y Tests 
Sa m ples m ust  be o btai ne d, pre- dial ysis, o n t he da y of t he visit f or all la b orat or y tests 
i de ntifie d i n Ta ble 7- 1 .  
Ot her e val uati o ns a n d tests perf or me d at Scree ni n g ( Visit 1) a n d ot her visits, as s pecifie d i n 
t he Sc he d ule of Assess me nts a n d Pr oce d ures (Secti o n 1. 3 ), will i ncl u de: 
 F S H test, if a p plica ble 
 Pre g na nc y test, if a p plica ble 
7. 3. 5. 1  
A nal ysis of Cli nical La b orat or y Tests 
A certifie d ce ntral la b orat or y wi ll be use d t o pr ocess a n d pro vi de res ults f or t he cli nical 
la b orat or y tests. T he baseli ne lab orat or y test res ults f or cli nical assess me nt f or a partic ular 
test will be defi ne d as t he last meas ure me nt pri or t o t he i nitial d ose of st u d y dr u g. 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 3 9 of 6 0 
F or a n y la b orat or y test val ue o utsi de t he refere nce ra n ge t hat  t he I n vesti gat or c o nsi ders 
cli nicall y si g nifica nt, t he I n vesti gat or will:  
 Re peat t he test t o verif y  t he o ut- of-ra n ge val ue. 
 F oll o w t he o ut- of-ra n ge val ue t o a satisfact or y cli nical res ol uti o n. 
 Rec or d as a n A E a n y la b orat or y test val ue t hat  
1)  is c o nfir me d a n d t he I n vesti gat or c onsi ders cli nicall y si g nifica nt, or  
2)  t hat re q uires a patie nt t o be disc o nti n ue d fr o m t he st u d y, or  
3)  t hat re q uires a patie nt t o recei ve n o n-st u d y treat me nt, or  
4)  f ulfills o ne or m ore criteria f or seri o us a d verse e ve nt ( S A E). 
T a ble 7- 1:  
Cli nic al L a b or at or y Tests 
He m at ol o g y a 
Ch em istry  b  
Oth er d  
He mat ocrit 
He m o gl o bi n 
Re d bl o o d cell ( R B C) c o u nt 
W hite bl o o d cell ( W B C) c o u nt 
Ne utr o p hils ( %) 
L y m p h oc ytes ( %) 
M o n oc ytes ( %) 
Bas o p hils ( %) 
E osi n o p hils ( %) 
Platelet c o u nt 
Al b u mi n 
Ala ni ne a mi n otra nsa mi nase ( A L T)  
As partate a mi n otra nsa mi nase ( A S T)  
Al kali ne p h os p hatase 
Bilir u bi n, t otal 
Bicar b o nate  
Bl o o d urea nitr o ge n ( B U N) 
Calci u m, t otal 
C hl ori de  
Creati ni ne 
Creati ne ki nase 
Gl uc ose 
Ma g nesi u m 
P h os p h or us c 
P otassi u m 
S o di u m  
Ser u m pre g na nc y 
i F G F 2 3 e 
P T H e 
a W h ole bl o o d. 
b Ser u m.  
c Ser u m p h os p h or us is perf or me d se paratel y fr o m sta n dar d cli nical la b orat or y tests at pr ot oc ol-s pecifie d ti me 
p oi nts. 
d F S H a n d ser u m pre g na nc y tests are perf or me d o n all fe males < 6 0 years of a ge u nless t here is a d oc u me nte d 
met h o d of sterilizati o n, or F S H te st c o nfir ms p ost- me n o pa usal stat us. 
e  Plas ma 
7. 4  
A d verse E ve nts 
T he I n vesti gat or is res p o nsi bl e f or e ns uri n g t hat a ll 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. 
A n A E is defi ne d as a n y u nt o war d me dica l occ urre nce i n a s u bject a d mi nistere d a 
p har mace utical pr o d uct d ur i n g t he c o urse of a cli nical i n vesti gati o n. A n A E ca n t heref ore be 
a n y u nfa v ora ble a n d u ni nte n de d si g n, s y m pt o m, or disease te m p or all y ass ociate d wit h t he use 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 4 0 of 6 0 
of a n i n vesti gati o nal pr o d uct, w het her or n ot t h o u g ht t o be relate d t o t he i n vesti gati o nal 
pr o d uct. 
Patie nts will be m o nit ore d t hr o u g h o ut t he st u d y f or A Es, fr o m Scree ni n g ( Visit 1) t hr o u g h 
t he e n d of t he st u d y. Me dical e ve nts t hat occ ur bef ore Scree nin g ( Visit 1) a n d are o n g oi n g at 
Scree ni n g ( Visit 1) s h o ul d be rec or de d as me dical hist or y, n ot A Es. All A Es s p o nta ne o usl y 
re p orte d b y t he patie 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 pers o n nel 
s uc h as “ 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?”, 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 A E e C 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. 
I n i nsta nces of well-rec o g nize d s y m pt o ms, t he y ca n be rec or de d as t he c o m m o nl y use d 
dia g n osis (e. g., fe ver, r u n n y n os e, a n d c o u g h ca n be rec or de d as “fl u”). H o we ver, if a 
dia g n osis is k n o w n, b ut 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 s h o ul d be rec or de d se paratel y. 
Eac h A E m ust be f oll o we d u ntil it is res ol ve d or  sta bilize d, or u ntil all atte m pts t o deter mi ne 
res ol uti o n of t he A E are e x hauste d. All A Es t hat are o n g oi n g at t he e n d of st u d y will be 
rec or de d as o n g oi n g i n t he e C R F. T he pr oce d ures s pecifie d i n Secti o n  7. 4. 7  are t o be 
f oll o we d f or re p orti n g S A Es. 
7. 4. 1  
Rec or di n g A d verse E ve nts 
A d verse e ve nts are t o be rec or de d o n t he A E  e C R F. Se verit y of a n A E will be gra de d 
acc or di n g t o t he f oll o wi n g defi niti o ns: 
 Mil d: T he patie nt e x perie nces a ware ness of s y m pt o ms b ut t hese are easil y t olerate d or 
ma na ge d wit h o ut s pecific treat me nt. 
 M o derate: T he patie nt e x perie nces disc o mf ort e n o u g h t o ca use i nterfere nce wit h us ual 
acti vit y, a n d/ or t he c o n diti o n re q uires s pecific treat me nt. 
 Se vere:  T he patie nt is i nca pacitate d wit h i na bil it y t o w or k or d o us ual acti vit y, a n d/ or t he 
e ve nt re q uires si g nifica n t treat me nt meas ures. 
Acti o n ta ke n wit h st u d y dr u g ( Te na pa n or or p h os p hate bi n der) d ue t o A Es will be 
cate g orize d as d ose n ot c ha n ge d, d ose re d uc e d, dr u g i nterr u pte d, dr u g wit h dra w n, or n ot 
a p plica ble.  Ot her acti o ns ta ke n d ue t o A Es will be cate g orize d as re q uire d c o nc o mita nt 
me dicati o n, re q uire d c o nc o mit a nt pr oce d ure, disc o nti n ue d fr o m st u d y, a n d/ or ot her. 
E ve nt o utc o me at res ol uti o n or ti me of last f oll o w- u p will be rec or de d as n ot rec o vere d/ n ot 
res ol ve d, rec o vere d/res ol ve d, rec o vere d/res ol ve d wit h se q uelae, rec o veri n g/res ol vi n g, fatal, 
or u n k n o w n. 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 4 1 of 6 0 
7. 4. 2  
Assess me nt of A d verse E ve nts 
T he relati o ns hi p of a n A E t o t he st u d y dr u g (te na pa n or or p h os p hate bi n der) s h o ul d be 
deter mi ne d b y t he I n vesti gat or acc or di n g t o t he f oll o wi n g criteria: 
 N ot relate d: T he e ve nt is m ost li kel y pr o d u ce d b y ot her fact ors s uc h as t he patie nt’s 
cli nical c o n diti o n, i nterc urre nt ill ness, or c o nc o mita nt me dicati o ns, a n d d oes n ot f oll o w a 
k n o w n res p o nse patter n t o t he st u d y dr u g, or t h e te m p oral relati o ns hi p of t he e ve nt t o 
st u d y dr u g a d mi nistrati o n ma kes a ca usal relati o ns hi p u nli kel y. 
 P ossi bl y relate d: T he e ve nt f oll o ws a reas o na b le te m p oral se q ue nce fr o m t he ti me of dr u g 
a d mi nistrati o n a n d is p ossi bl y d ue t o dr u g a d mi nistrati o n a n d ca n n ot be reas o na bl y 
e x plai ne d b y ot her fact ors s uc h as t he patie n t’s cli nical c o n diti o n, i nterc urre nt ill ness, or 
c o nc o mita nt me dicati o ns. 
 Relate d: T he e ve nt f oll o ws a reas o na ble te m p oral se q ue nce fro m t he ti me of dr u g 
a d mi nistrati o n, a n d/ or f oll o ws a k n o w n res p o ns e patter n t o t he st u d y dr u g, a n d ca n n ot be 
reas o na bl y e x plai ne d b y ot her factors s uc h as t he patie nt’s cl i nical c o n diti o n, i nterc urre nt 
ill ness, or c o nc o mita nt me dicati o ns. 
7. 4. 3  
F oll o wi n g A d verse E ve nts 
All ( b ot h seri o us a n d n o n-seri o us) A Es m ust be f oll o we d u ntil t he y are res ol ve d or sta bilize d, 
t he c o n diti o n bec o mes c hr o nic i n nat ure, all atte m pts t o deter mi ne res ol uti o n of  t he A E are 
e x ha uste d, or t he patie nt dies. T he I n vesti gat or s h o ul d use his/ her di screti o n i n or deri n g 
a d diti o nal tests as necessar y t o m o nit or t he res ol uti o n of s uc h A Es. 
7. 4. 4  
Disc o nti n u ati o n d ue t o A d verse E ve nt 
A n y patie nt w h o e x perie nces a n A E ma y be wit h dra w n at a n y ti me fr o m t he st u d y at t he 
discreti o n of t he I n vesti gat or. F or eac h pa tie nt wit h dra w n fr o m t he st u d y d ue t o a n A E, 
w het her seri o us or n o n-seri o us, t he A E s h o ul d be n ote d o n t he A d verse E ve nts C R F a n d 
s h o ul d be f oll o we d u ntil t he A E is res ol ve d or sta bilize d, t he c o n diti o n bec o mes c hr o nic i n 
nat ure, all atte m pts t o deter mi ne res ol uti o n of  t he A E are e x ha uste d, or t he patie nt dies. A 
decisi o n t o disc o nti n ue a patie nt d ue t o a n A E s h o ul d be disc usse d wit h t he Me dical M o nit or. 
If t he A E ma y relate t o o ver d ose of st u d y dr u g, t he I B s h o uld be c o ns ulte d f or details 
re gar di n g a n y s pecific acti o ns t o be ta ke n. 
7. 4. 5  
Pre g n a nc y 
Fe male patie nts m ust be i nstr ucte d t o disc o nt i n ue all st u d y dr u g a n d i nf or m t he I n vesti gat or 
i m me diatel y if t he y bec o me pre g na nt d uri n g t he st u d y. 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 4 2 of 6 0 
T he I n vesti gat or m ust re p ort a n y pre g na nc y t o I n Cli n Safet y wit hi n 1 b usi ness da y of 
bec o mi n g a ware of it. T he patie nt m ust be i m me diatel y disc o nti n ue d fr o m f urt her treat me nt 
wit h st u d y dr u g. A n u nc o m plicate d pre g na nc y will n ot be c o nsi dere d a n A E or S A E, b ut all 
pre g na ncies will be f oll o we d t hr o u g h birt h. 
Pre g na ncies are ca pt ure d if t he y occ ur i n fe male  patie nts or i n t he sex ual part ners of male 
patie nts fr o m t he ti me t he patie nt is first e x p os e d t o t he st u d y dr u g u ntil 3 0 da ys after last 
e x p os ure t o t he st u d y dr u g. 
A n y c o n ge nital a b n or malitie s i n t he offs pri n g of a patie nt w h o recei ve d st u d y dr u g will be 
re p orte d as a n S A E. T he o utc o me of a n y preg na nc y a n d t he prese nce or a bse nce of a n y 
c o n ge nital a b n or malit y will be rec or de d i n t he s o urce d oc u me ntati o n a n d re p orte d t o I n Cli n 
Safet y. 
7. 4. 6  
Seri o us A d verse E ve nts 
A n S A E is a n y A E occ urri n g fr o m Scree ni n g t h r o u g h t he e n d of t he st u d y, at a n y d ose t hat 
res ults i n a n y of t he f oll o wi n g o utc o mes: 
 Deat h 
 A life-t hreate ni n g a d verse dr u g e x perie nce 
 I n patie nt h os pitalizati o n or pr olo n gati o n of e xisti n g h os pitalizati o n 
 A persiste nt or si g nifi ca nt disa bilit y/i nca pacit y 
 A c o n ge nital a n o mal y/ birt h defect 
I m p orta nt me dical e ve nts t hat ma y n ot res ult i n deat h, be life t hreate ni n g, or re q uire 
h os pitalizati o n ma y be c o nsi der e d a n S A E w he n, base d u p o n a p pr o priate me dical j u d g me nt, 
t he y ma y je o par dize t he patie nt a n d ma y re q uire me dical or s ur gical i nter ve nti o n t o pre ve nt 
a n y of t he o utc o mes liste d i n t his defi niti o n. E xa m ples of s uc h me dical e ve nts i ncl u de 
aller gic br o nc h os pas m re q uiri n g 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, bl o o d 
d yscrasias or c o n v ulsi o ns t hat d o n ot res ult i n i n patie nt h os pitalizati o n, or t he de vel o p me nt of 
dr u g de pe n de nc y or dr u g a b use. 
N ote:  S A Es re q uire i m me diate re p orti n g t o I n Cli n Safet y. See “ Rep orti n g Seri o us A d verse 
E ve nts” bel o w f or details. 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 4 3 of 6 0 
7. 4. 7  
Re p orti n g Seri o us A d verse E ve nts 
I n t he e ve nt of a n y S A E re p orted or o bser ve d d uri n g t he st u d y, w het her or n ot attri b ut a ble 
t o t he st u d y dr u g, site pers o n nel will re p ort it t o I n Cli n Dr u g Safet y wit hi n 2 4 h o urs of t he 
k n o wle d ge of t he occ urre nce. 
T o re p ort a n S A E, c o m plete t he st u d y s pecifi c Seri o us A d verse E ve nt Re p ort F or m a n d e mail 
 T he S A E i nf or mati o n will be e ntere d i nt o t he E D C s yste m a n d t he 
A E will mar ke d as “seri o us”. T his will tri g ger a n  e mail n otificati o n alert t o t he tea m t hat a n 
S A E has occ urre d.  
Rec o nciliati o n of S A E i nf or mati o n i n t he E D C wit h t he S A E i nf or mati o n recei ve d a n d 
e ntere d i n t he Ar g us data base will be perf or m e d per t he I n Cli n Data  Ma na ge me nt Pla n.  
Safet y C o ntact I nf or mati o n: 
 
  
 I n vesti gat or is re q uire d t o s u b mit S A E re p orts t o t he I R B/I n de pe n de nt Et hics C o m mittee 
(I E C) i n acc or da nce wit h l ocal re q uire me nts. All I n vesti gat ors c urre ntl y i n v ol ve d i n cli nical 
trials of te na pa n or will recei ve safet y alert n otificati o ns f or s u b missi o n t o t heir l ocal I R B/I E C 
as re q uire d. All re p orts se nt t o I n vesti gat ors will bli n d t he treat me nt assi g n me nt. 
F oll o w- U p of S A E: 
T he I n vesti gat or m ust c o nti n ue t o f oll o w t he patie nt u ntil t he S A E has res ol ve d or sta bilizes 
(i n t he case of persiste nt i m pair me nt), t he c o n diti o n bec o mes c hr o nic i n nat ure, all atte m pts 
t o deter mi ne res ol uti o n of t he e ve nt are e x ha uste d, or t he patie nt dies.   
7. 5  
Effic ac y E n d p oi nts 
Efficac y meas ures i n t his st u d y i ncl u de s- P (t o be meas ure d at all sc he d ule d visits e xce pt 
Visit 2), i F G F 2 3, P T H, me dicati o n d ose, pill n u m ber, pill wei g ht, a n d ot her i nf or mati o n 
relati ve t o dr u g usa ge (e. g., % o n m o n ot hera p y), an d patie nt e x perie nce. 
T he f oll o wi n g efficac y e n d p oi nts will be a nal yze d  b y c o h ort a n d f or t he e ntire F A S at eac h 
p ost- baseli ne visit ( o nl y f or s- P e n d p oi nts), t he e n d p oi nt visit of t he Treat me nt Peri o d, a n d t he 
e n d p oi nt visit of t he e ntire st u d y: 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 4 4 of 6 0 
 s- P res p o nse: ac hie vi n g or mai ntai ni n g s- P ≤5. 5 m g/ d L 
 N or mal s- P res p o nse: ac hie vi n g s- P ≤4. 5 m g/ d L 
 B or derli ne s- P res p o nse: ac hie vi n g or mai ntai ni n g s- P ≤6. 5 m g/ d L 
 C ha n ge fr o m baseli ne i n s- P 
 Relati ve c ha n ge fr o m baseli ne i n i F G F 2 3, deri ve d as “c ha n ge fr o m baseli ne i n 
i F G F 2 3/ baseli ne i F G F 2 3” 
 C ha n ge fr o m baseli ne i n P T H 
 C ha n ge fr o m baseli ne i n t otal dail y d ose of P T H- m o di f yi n g me dicati o ns ( m g) 
 
T he f oll o wi n g efficac y e n d p oi nts will als o be a nal yze d b y c o h ort a n d f or t he e ntire “ F A S 
( C o h orts 1- 2)” at eac h p ost- baseli ne visit. t he e n d p oi nt visit of t he Treat me nt Peri o d, a n d t he 
e n d p oi nt visit of t he e ntire st u d y: 
 C ha n ge fr o m baseli ne i n t otal dail y d ose of p h os p h or us-l o weri n g me dicati o n ( m g) 
(te na pa n or a n d p h os p hate bi n der c o m bi ne d) 
 C ha n ge fr o m baseli ne i n t otal dail y pill wei g ht (te na pa n or a n d p h os p hate bi n der 
c o m bi ne d) 
 C ha n ge fr o m baseli ne i n t otal dail y pill n u m ber (te na pa n or a n d p h os p hate bi n der 
c o m bi ne d) 
 Me dicati o n d ose res p o nse: ac hie vi n g at le ast 3 0 % re d ucti o n fr o m baseli ne i n t otal 
dail y d ose ( m g) of p h os p h or us-l o weri n g me dicati o n 
 Pill wei g ht res p o nse: ac hie vi n g at least 3 0 % re d ucti o n fr o m baseli ne i n t otal dail y pill 
wei g ht 
 Pill n u m ber res p o nse: ac hie vi n g at least 3 0 %  re d ucti o n fr o m baseli ne i n t otal dail y 
pill n u m ber (e. g., re d uce fr o m 6 pills at baseli ne t o ≤4 pills a n d re d uce fr o m 9 pills at 
baseli ne t o ≤6 pills) 
 Pill b ur de n res p o nse: ac hie vi n g pill wei g ht res p o nse a n d pill n u m ber res p o nse 
 s- P a n d me dicati o n d ose res p o nse: ac hie vi n g s- P res p o nse a n d me dicati o n d ose 
res p o nse 
 s- P a n d pill wei g ht res po nse: ac hie vi n g s- P res p o nse a n d pill wei g ht res p o nse 
 s- P a n d pill n u m ber res p o nse: ac hie vi n g s- P res p o nse a n d pill n u m ber res p o nse 
 s- P a n d pill b ur de n res p o nse: ac hie vi n g s- P res p o nse, pill wei g ht res p o nse, a n d pill 
n u m ber res p o nse  
 N or mal s- P a n d me dicati o n d ose res p o nse: ac hie vi n g n or mal s- P res p o nse a n d 
me dicati o n d ose res p o nse 
 N or mal s- P a n d pill wei g ht res p o nse: ac h ie vi n g n or mal s- P res p o nse a n d pill wei g ht 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 4 5 of 6 0 
res p o nse 
 N or mal s- P a n d pill n u m ber res p o nse: ac h ie vi n g n or mal s- P res p o nse a n d pill n u m ber 
res p o nse 
 N or mal s- P a n d pill b ur de n res p o nse: ac hie vi n g n or mal s- P res p o nse, pill wei g ht 
res p o nse, a n d pill n u m ber res p o nse 
 B or derli ne s- P a n d me dicati o n d ose res p o nse: ac hie vi n g b or derli ne s- P res p o nse a n d 
me dicati o n d ose res p o nse 
 B or derli ne s- P a n d pill we i g ht res p o nse: ac hie vi n g b or derli ne s- P res p o nse a n d pill 
wei g ht res p o nse 
 B or derli ne s- P a n d pill n u m ber res p o nse: ac hie vi n g b or derli ne s- P res p o nse a n d pill 
n u m ber res p o nse 
 B or derli ne s- P a n d pill b ur de n res p o nse: ac hie vi n g b or derli ne s- P res p o nse, pill 
wei g ht res p o nse, a n d pill n u m ber res p o nse 
T he fi nal list of efficac y e n d p oi nts will be pr o vi de d i n t he statistical a nal ysis pla n ( S A P). 
8  
M E T H O D O L O G Y/ S T U D Y VI SI T S 
8. 1  
P atie nt E d uc ati o n 
A patie nt e d ucati o n pr o gra m wi ll be use d as a sta n dar d met h o d t o e d ucate patie nts o n 
te na pa n or at Scree ni n g ( Visit 1) a n d Ra n d o mizatio n/ E nr oll me nt ( Visit 2) a n d will i ncl u de t he 
f oll o wi n g i nf or mati o n: 
 Basic i nf or mati o n a b o ut te na pa n or 
 H o w t o ta ke te na pa n or 
 P ossi ble i ncrease d b o wel m o ve me nt fre q ue nc y a n d/ or l o os er st o ol wit h te na pa n or, 
a n d reas o n f or t hese p ote ntial c ha n ges 
 W hat t o e x pect if c ha n ges i n st o ol fre q ue nc y a n d st o ol f or m o cc ur wit h te na pa n or  
o  W he n li kel y t o occ ur  
o  H o w l o n g li kel y t o last (tra nsie nt)  
o  Se verit y ( mil d t o m o derate)  
o  M ost patie nts re mai n i n “ n or mal” ra n ge  
o  M ost patie nts sta y o n t hera p y  
T he patie nt e d ucati o n pr o gra m will als o i ncl u de  s pecific g ui da nce o n h o w t o ma na ge t he si de 
effect pr ofile of te na pa n or a n d i ncl u de t he f oll o wi n g i nf or mati o n: 
 E ns ure patie nt has st o p pe d ta ki n g a n y st o ol s ofte ner, la xati ve, ma g nesi u m, or 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 4 6 of 6 0 
l u brica nt bef ore starti n g te na pa n or 

Pr o vi de rec o m me n dati o n t o ta ke I m o di u m or  ot her o ver-t he-c o u nter a nti- diarr heal
me dici ne, if nee de d
All patie nt-faci n g e d ucati o na l materials will be a p pr o ved b y t he I R B pri or t o use. 
8. 2  
P atie nt E x perie nce Assess me nt 
Patie nts will be as ke d a b o ut t heir e x perie n ce wit h p h os p h or us ma na ge me nt r o uti ne d uri n g 
st u d y c o m pare d t o bef ore st u d y. T he assessme nt will be c o n d ucte d via a n e P R O 
q uesti o n naire at Visit 9/ Earl y Ter mi nati o n (e n d of Part A).  
8. 3  
Scree ni n g Pr oce d ures: Visit 1 ( D a y - 2) 
T he I n vesti gat or will i nf or m ea c h pr os pecti ve patie nt of t he nat ure of t he st u d y, e x plai n t he 
p ote ntial ris ks, a n d o btai n writte n i nf or me d c o nse nt fr o m t he patie nt pri or t o perf or mi n g a n y 
st u d y-relate d pr oce d ures.  
Scree ni n g e val uati o ns will c o nsist of t he f oll o wi n g: 

Assess me nt of disease stat us o utli ne d  i n t he i ncl usi o n/e xcl usi o n criteria

Date of birt h, se x, race, a n d et h nicit y

Wei g ht ( pre- dial ysis) a n d hei g ht  ( k g a n d c m, res pecti vel y)

Kt/ V – t he m ost rece nt val ue pri or  t o Scree ni n g

Me dical a n d s ur gical hist or y

P h os p hate bi n der c urre ntl y use d a n d prescri be d  dail y d ose ( m ust be t hree ti mes a da y)

P h ysical e xa mi nati o n

Vital si g ns ( pre- dial ysis)

Electr ocar di o gra m e val uati o n

Bl o o d sa m ples f or s- P, i F G F 2 3, P T H, cli nical la b orat or y c he mistr y a n d he mat ol o g y tests, 
a n d bi o mar ker a nal ys is ( pre- dial ysis)

F S H a n d pre g na nc y te st, if a p plica ble

e Diar y (i nstr ucti o ns a n d be gi n ni n g of data e ntr y f or st o ol fre q ue nc y a n d c o nsiste nc y)

Pri or/c o nc o mita nt me dicati o ns; s pecial atte n ti o n s h o ul d be gi ve n t o me dicati o ns t o be  
d isc onti n ue d bef ore starti n g te na pa n or (see A p pe n di x I ). A n y use of P T H- m o dif yi n g 
me d icati o ns i n t he past 3 0 da ys nee d t o be a de q uatel y rec or de d i n t he Pri or/ C o nc o mita nt 
Me dicati o ns e C R F.


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 4 7 of 6 0 

Patie nt e d ucati o n o n i nf or mati o n a b o ut te na pa n or , h o w t o ta ke te na pa n or, w hat t he y ma y
e x perie nce o n te na pa n or, me dicati o ns t o be disc o nti n ue d bef ore starti n g te na pa n or, a n d
h o w best t o ma na ge a p ossi ble i ncrease i n b o wel m o ve me nt fre q ue nc y a n d/ or l o ose st o ol
if b ot hers o me (e. g., use of o ver-t he-c o u nter a nti- diarr heal), etc
Patie nts will be i nstr ucte d n ot t o ta ke a n y ot her me dicati o ns wit h o ut  t he a p pr o val of t he 
I n vesti gat or. Res ults of t he scree ni n g e val uati o ns m ust meet t h e i ncl usi o n/e xcl usi o n criteria 
f or t he patie nt t o c o nti n ue i n t he st u d y. 
8. 4  
Tre at me nt Peri o d: Visit 2 ( D a y 1) 

I ncl usi o n/e xcl usi o n criteria (assess s- P criteria usi n g t he s-P meas u re me nt at Visit 1 a n d  
c o nfir m ot her a p plica ble i n cl usi o n/e xcl usi o n criteria)

Ra n d o mizati o n ( C o h orts 1- 2) or  e nr oll me nt ( C o h ort 3)

Me dical/s ur gical hist or y (rec or d o nl y c ha n ges t o me dical hist or y fr o m Visit 1)

e Diar y (i nstr ucti o ns a n d re vi e w of data e ntr y f or st o ol fre q ue nc y a n d c o nsiste nc y;  
rei nf orce t he  nee d t o c o m plete dail y)

Pri or/c o nc o mita nt me dicati o ns; s pecial atte n ti o n s h o ul d be gi ve n t o me dicati o ns t o be  
d isc onti n ue d bef ore starti n g te na pa n or (see A p pe n di x I ). A n y ne w P T H- m o dif yi n g 
me di cati o n use or c ha n ges t o e xisti n g P T H- m o dif yi n g me dicati o n use si n ce Scree ni n g 
n ee d t o be a de q uatel y rec or de d  i n t he Pri or/ C o nc o mita nt Me dicati o ns  e C R F.

Patie nt  e d ucati o n

St u d y dr u g dis pe nsi n g

A E assess me nt
8. 5  
Tre at me nt Peri o d: Visits 3, 4, 5, 6, 7 a n d 8 ( D a ys 8, 1 5, 2 2, 2 9, 4 3, a n d 5 7 ± 2 
D a ys) 

Ser u m p h os p h or us meas ure me nt ( pre- dial ysis)

e Diar y (re vie w d ata e ntr y a n d rei nf orce t he nee d t o c o m plete dail y)

St u d y dr u g dis pe nsi n g a n d/ or  ret ur n, if a p plica ble

C o nc o mita nt  me dicati o ns; s pecial atte nti o n sh o ul d be gi ve n t o pr o hi bite d  c o nc o mita nt  
me dicati o ns  (see A p pe n di x I ). A n y ne w P T H- m o dif yi n g me dicati o n use or c ha n ges t o 
e xisti ng P T H- m o di f yi n g me dicati o n use  si nce t he pre vi o us assess me nt of c o nc o mita nt 
me dicati o ns nee d t o be a de q uatel y rec or de d  i n t he Pri or/ C o nc o mita nt Me dicati o n s e C R F.


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 4 8 of 6 0 

A E assess me nt
8. 6  
E n d of Tre at me nt Peri o d or St art of  E xte nsi o n Peri o d: Visit 9 ( D a y 7 1 ± 2 
D a ys) 

Wei g ht ( pre- dial ysis)

P h ysical e xa mi nati o n

Vital si g ns ( pre- dial ysis)

Electr ocar di o gra m e val uati o n

Bl o o d sa m ples f or s- P, i F G F 2 3, P T H, cli nical la b orat or y c he mistr y a n d he mat ol o g y tests,
a n d bi o mar ker a nal ys is ( pre- dial ysis)

Pre g na nc y test (f or w o me n of c hil d- beari n g p ote ntial)

St u d y dr u g dis pe nsi n g a n d/ or ret ur n, if a p plica ble

e Diar y (re vie w data e ntr y)

Patie nt e x perie nce assess me nt

C o nc o mita nt me dicati o ns; s pecial atte nti o n s h o ul d be gi ve n t o pr o hi bite d c o nc o mita nt
me dicati o ns (see A p pe n di x I ). A n y ne w P T H- m o dif yi n g me dicati o n use or c ha n ges t o
e xisti n g P T H- m o dif yi n g me dicati o n use si nce t he pre vi o us assess me nt of c o nc o mita nt
me dicati o ns nee d t o be a de q uatel y rec or de d i n t he Pri or/ C o nc o mita nt Me dicati o ns e C R F.

A E assess me nt
8. 7  
O pti o n al E xte nsi o n Peri o d: Visits 1 0, 1 1, a n d 1 2 ( D a ys 1 0 1, 1 3 1, a n d 1 6 1 ± 
7 D a ys) 

Ser u m p h os p h or us meas ure me nt ( pre- dial y sis)

St u d y dr u g dis pe nsi n g a n d/ or  ret ur n, if a p plica ble

C o nc o mita nt  me dicati o ns; s pecial atte nti o n sh o ul d be gi ve n t o pr o hi bite d  c o nc o mita nt  
me dicati o ns  (see A p pe n di x I ). A n y ne w P T H- m o dif yi n g me dicati o n use or c ha n g es t o 
e xisti n g P T H- m o di f yi n g me dicati o n use si nce t he pre vi o us assess me nt of c o nc o mita nt 
me dicati o ns nee d t o be a de q uatel y rec or de d  i n t he Pri or/ C o nc o mita nt Me dicati o ns e C R F.

A E assess me nt
8. 8  
E n d of E xte nsi o n Peri o d: Visit 1 3 ( D a y 1 9 1 ± 7 D a ys) 

Wei g ht ( pre- dial ysis)

P h ysical e xa mi nati o n

Vital si g ns ( pre- dial ysis)


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 4 9 of 6 0 
 Electr ocar di o gra m e val uati o n 
 Bl o o d sa m ples f or s- P, i F G F 2 3, P T H, cli nical la b orat or y c he mistr y a n d he mat ol o g y tests, 
a n d bi o mar ker a nal ys is ( pre- dial ysis) 
 Pre g na nc y test (f or w o me n of c hil d- beari n g p ote ntial) 
 St u d y dr u g ret ur n 
 C o nc o mita nt me dicati o ns; s pecial atte nti o n s h o ul d be gi ve n t o pr o hi bite d c o nc o mita nt 
me dicati o ns (see A p pe n di x I ). A n y ne w P T H- m o dif yi n g me dicati o n use or c ha n ges t o 
e xisti n g P T H- m o dif yi n g me dicati o n use si nce t he pre vi o us assess me nt of c o nc o mita nt 
me dicati o ns nee d t o be a de q uatel y rec or de d i n t he Pri or/ C o nc o mita nt Me dicati o ns e C R F.   
 A E assess me nt 
8. 9  
E arl y Ter mi n ati o n Visit  
If p ossi ble, all assess me nts a n d proce d ures sc he d ule d f or Visit 9 ( Secti o n 8. 6 ) e xce pt st u d y 
dr u g dis pe nsi n g will be c o m plete d at t he Earl y Ter mi nati o n visit f or patie nts w h o 
pre mat urel y disc o nti n ue fr o m t he st u d y bef ore Visit 9; t h ose sc he d ule d f or Visit 1 3 
(Secti o n 8. 8 ) will be c o m plete d at t he Earl y Ter mi nati o n visit f or patie nts w h o pre mat urel y 
disc o nti n ue fr o m t he st u d y be t wee n Visit 9 a n d Visit 1 3. 
8. 1 0  
Wit h dr a w al Pr oce d ures 
I n t he e ve nt of a patie nt’s with dra wal f or a n y reas o n, e ver y eff ort  will be ma de t o c o m plete 
t he Earl y Ter mi nati o n visit. At t he Earl y Ter mi nati o n visit, assess me nts a n d pr oce d ures 
sc he d ule d f or t he last sc he d ule d visit i n Part A ( Visit 9; e xce pt st u d y dr u g dis pe nsi n g) or 
Part B ( Visit 1 3) will be perf or me d a n d are de pe n de nt u p o n w het her t he patie nt’s wit h dra wal 
occ urs i n Part A or Part B ( Secti o n 8. 9 ).  
Eac h wit h dra w n patie nt wit h o n g oi n g A E(s) at  st u d y wit h dra wal will be f oll o we d u ntil t he 
A E(s) are res ol ve d or sta bilize d, t he c o n diti o n bec o mes c hr o nic i n nat u re, all atte m pts t o 
deter mi ne res ol uti o n of t he A E(s) ar e e x ha uste d, or t he patie nt dies.  
8. 1 1  
Criteri a f or St u d y Ter mi n ati o n 
T he st u d y ma y be ter mi nate d at a n y ti me b y t he S p o ns or f or reas o ns i ncl u di n g b ut n ot li mite d 
t o t he f oll o wi n g: (i) if S A Es occ ur, (ii) if, i n t he S p o ns or’s j u d g me nt, t here are n o f urt her 
be nefits t o be ac hie ve d fr o m t he st u d y, or (i ii) f or a d mi nistrati ve reas o ns. A site ma y be 
cl ose d o ut if t he I n vesti gat or d oes n ot a d here t o t he pr ot oc ol. I n t he e ve nt t hat t he cli nical 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 5 0 of 6 0 
de vel o p me nt of t he i n vesti ga ti o nal pr o d uct is disc o nti n ue d, t he S p o ns or s hall i nf or m all 
I n vesti gat ors/i nstit uti o ns partici pati n g i n t he st u d y c o n d uct a n d t he I R B o verseei n g t he st u d y. 
8. 1 2  
T ot al Bl o o d V ol u me Re q uire d f or St u d y 
T he a p pr o xi mate bl o o d v ol u me re q uire d at sc he d ule d visits f or eac h patie nt is s h o w n i n t he 
f oll o wi n g ta ble: 
T a ble 8- 1:  
A p pr o xi m ate Bl o o d V ol u me per P atie nt ( P arts A a n d B C o m bi ne d) 
Test 
N o. of S a m ples 
V ol u me C ollecte d 
f or E ac h S a m ple 
( m L)
T ot al ( m L)
C he mistr y + F S H 
3 
7 
2 1 
He mat ol o g y ( bl o o d) 
3 
3 
9 
P h os p h or us (ser u m) 
1 2 
4 
4 8 
P T H ( plas ma) 
3 
4 
1 2 
i F G F- 2 3 ( plas ma) 
3 
4 
1 2 
Ser u m bi o mar kers 
3 
5 
1 5 
Plas ma bi o mar kers 
3 
6 
1 8 
T ot a l
-- 
-- 
1 3 5
8. 1 3  
Pr ot oc ol De vi ati o ns 
Patie nts m ust f ull y meet t he eli g i bilit y criteria i n or der t o be e nr olle d i n t he st u d y. Ar del y x 
d oes n ot gra nt pr ot oc ol wai vers t o  i ncl usi o n/e xclusi o n criteria. 
A pr ot oc ol de viati o n is defi ne d as a n y i nte nti o nal or u ni nte nti o nal c ha n ge t o, or 
n o nc o m plia nce wit h, t he a p pr o ve d pr ot oc ol pr oce d ures or re q uire me nts. De viati o ns ma y 
res ult fr o m t he acti o n or i nacti o n of t he patie nt, t he I n vesti gat or , or site staff. E xa m ples of 
de viati o ns i ncl u de, b ut are n ot li mite d t o:  

E nr olli n g a patie nt t hat d oes n ot  meet st u d y eli gi bilit y criteria

Use of me dicati o ns, f o o d, dri n k, her bal re me dies, or s u p ple me nts t hat are s pecificall y 
p r o hi bite d i n t he prot oc ol (see  A p pe n di x I )

Misse d or o ut- of- wi n d o w visits

St u d y dr u g n ot a d mi nistere d per  pr ot oc ol

Fail ure  t o a d here t o t he sc he d ule of assess me nts


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 5 1 of 6 0 
 Fail ure t o c o m pl y wit h re g ulat or y re q uire me nts f or patie nt safet y 
A pr ocess f or defi ni n g a n d ha n dli n g pr ot oc ol de viati o ns will be esta blis he d f or t his st u d y. 
T he pr ocess will i ncl u de t he defi niti o n of “cr itical” pr ot oc ol de viati o n a n d ste ps f or 
i m me diate n otificati o n of t he “critical” pr ot ocol de viati o n t o t he Me dical M o nit or a n d t he 
S p o ns or. T he I n vesti gat or is res p o nsi ble f or se ei n g t hat all k n o w n pr ot oc ol de viati o ns are 
rec or de d a n d ha n dle d a p pr o priatel 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 A n al ysis Pl a n 
A f or mal S A P will be pr o vi de d se paratel y. If t h e la n g ua ge i n t his pr ot oc ol a n d t he la n g ua ge 
i n t he S A P differ, t he S A P g o ver ns. Res ults o btai ne d fr o m t he a nal yses s pecifie d i n t he fi nal 
a p pr o ve d versi o n of t he S A P will bec o me t he basis of t he cli nical st u d y re p ort f or t his st u d y. 
A n y de viati o ns fr o m t he fi nal a p pr o ve d versi o n of t he S A P will be d oc u me nte d i n t he cli nical 
st u d y re p ort. 
9. 2  
Deter mi n ati o n of S a m ple Size 
A p pr o xi matel y 3 0 0 C K D patie nts o n dial ysis a n d sta ble p h os p hate bi n der t hera p y will be 
ra n d o mize d i n a 1: 1 rati o t o C o h ort 1 or C o h ort 2 ( ~ 1 5 0 patie n ts/c o h ort); a n d a p pr o xi matel y 
3 0 p h os p hate bi n der naï ve patie nts wit h C K D o n  dial ysis will be e nr olle d i nt o C o h ort 3. 
O verall, a p pr o xi matel y 3 3 0 patie nts wit h C K D o n dial ysis will be ra n d o mize d or e nr olle d i n 
t his st u d y. T he sa m ple size of t his st u d y is n ot pla n ne d base d o n statistical c o nsi derati o ns. 
9. 3  
A n al ysis P o p ul ati o ns 
T he a nal ysis p o p ulati o ns defi ne d f or t his st u d y i ncl u de: I n te nt-t o- Treat (I T T) p o p ulati o n, 
Safet y P o p ulati o n, F ull A nal ysis Se t ( F A S), a n d F A S ( C o h orts 1- 2).  
 I nte nt-t o- Treat P o p ulati o n: will be c o m prised of all ra n d o mize d or  e nr olle d patie nts.  
 Safet y P o p ulati o n: will i ncl u de all I T T patie nts w h o recei ve at least o ne d ose of st u d y 
dr u g. It will be t he a nal ysis p o p ulati o n f o r safet y a n d t olera bilit y a nal yses.  
 F ull A nal ysis Set: will i ncl u de all I T T pa tie nts w h o meet t he stu d y e ntr y eli gi bilit y 
criteria, recei ve at least o n e d ose of st u d y dr u g, a n d ha ve at least o ne p ost- baseli ne s- P 
meas ure me nt d uri n g t he st u d y. It  will be t he p o p ulati o n use d f or efficac y a nal yses.  
 F ull A nal ysis Set ( C o h orts 1- 2): will i ncl u de all F A S patie nts i n C o h ort 1 a n d C o h ort 2. It 
will be t he p o p ulati o n use d f or a nal yses of efficac y e n d p oi nts a p plic a ble t o C o h ort 1 a n d 
C o h ort 2 o nl y. 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 5 2 of 6 0 
9. 4  
St atistic al Met h o ds 
9. 4. 1  
Ge ner al C o nsi der ati o ns  
All meas ures will be s u m marize d descri pti vel y b y c o h ort. Descri pti ve statistics i ncl u di n g t he 
n u m ber of o bser vati o ns ( n), mea n, sta n dar d  de viati o n, me dia n, mi ni m u m, a n d ma xi m u m will 
be prese nte d f or c o nti n u o us varia bles. S u m ma r y statistics f or i FG F 2 3 will als o i ncl u de 
ge o metric mea n a n d ge o metric c oefficie nt of va riati o n %. Fre q ue nc y ( n) a n d perce nt ( %) will 
be prese nte d f or cate g orical varia bles. 
I n di vi d ual patie nt data i ncl u di n g releva nt deri ve d varia bles will be liste d. 
A nal yses of efficac y e n d p oi nts will be perf or m e d o n t he F A S a n d s u bsets of F A S. A nal yses 
of safet y a n d t olera bilit y meas ures will be perf or me d o n t he Sa fet y p o p ulati o n. T he statistical 
testi n g, if a n y, will be c o n d ucte d at a sig nifica nce le vel of 0. 0 5 (t w o-si de d).  
9. 4. 2  
B aseli ne Descri pti ve St atistics 
Baseli ne c haracteristics, i ncl u di n g de m o gra p hics , disease c haracteristics, pri or/c o nc o mita nt 
me dicati o ns, a n d me dical/s ur gi cal hist or y will be s u m mari ze d b y c o h ort a n d o verall f or 
rele va nt a nal ysis set(s).  
9. 4. 3  
Effic ac y A n al ysis 
All efficac y meas ures a n d e n d p oi nts will be descri pti vel y s u m marize d at eac h visit b y c o h ort 
a n d f or t he c orres p o n di n g a nal ysis set. 
F or res p o nse e n d p oi nts, t he res p o nse  rate at eac h p ost- baseli ne visit will be esti mate d wit h 
as y m pt otic 9 5 % c o nfi de nce i nter v al f or eac h c o h ort. F or e x pl orat or y p ur p oses, i nfere ntial 
a nal yses ma y be perf or me d f or c o m paris o ns of c o nti n u o us a n d bi nar y e n d p oi nts bet wee n 
c o h orts. N o m ulti plicit y a dj u st me nt will be i m ple me nte d.  
S u b gr o u p a nal yses b y a ge, se x, race, p h os p hate bi n der t y pe, baseli ne s- P, a n d e n di n g t hera p y 
cate g or y (e. g., te na pa n or al o ne, te na pa n or + ≤3 ta blets/ da y p h os p hate bi n der, or te na pa n or + 
> 3 ta blets/ da y p h os p hate bi n der) will als o  be perf or me d f or selecti ve e n d p oi nts. 
A nal yses will be detaile d i n t he S A P.    
9. 4. 4  
H a n dli n g of Missi n g D at a 
Descri pti ve s u m maries of efficac y a n d safet y/t o lera bilit y meas ures will be base d o n o bser ve d 
data. N o i m p utati o n of missi n g data will be i m ple me nte d.  
Ha n dli n g of missi n g data f or i nfere ntial a nal yses will be detaile d i n t he S A P.   


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 5 3 of 6 0 
9. 4. 5  
A dj ust me nts f or C o v ari ates 
I n ge neral, t he t w o ra n d o mizati o n stratificati o n fact ors (t y pe of p h os p hate bi n der a n d s- P 
le vel at Visit 1) will be a dj uste d i n i nfere ntial a nal yses of efficac y e n d p oi nts o n F A S 
( C o h orts 1- 2). Baseli ne val ue ma y als o be a dj uste d if a p plica ble. Detaile d i nf or mati o n o n 
c o variate a dj ust me nt will be pr o vi de d i n t he S A P.  
9. 4. 6  
Visit Wi n d o ws 
N o a nal ysis visit wi n d o ws will be f or mall y defi ne d. T he sc he d ule of assess me nts a n d 
pr oce d ures i n  Secti o n 1. 3 details t he i nte n de d c ollecti o n of st u d y varia bles at s pecifie d visits. 
Data c ollecte d at a sc he d ule d visit will be use d  as t he data at t he c orres p o n di n g a nal ysis visit 
e ve n if t he visit is o ut- of- w i n d o w. T o mi ni mize t he a m o u nt of missi n g data, data c ollecte d at 
a n u nsc he d ule d visit will be ma p pe d t o a n a nal ysis visit base d o n a nal ysis wi n d o ws if data at 
t he c orres p o n di n g sc he d ule d visit are n ot a vaila ble. Si milarl y, data fr o m t he Earl y 
Ter mi nati o n visit ma y als o be ma p pe d. Detail e d i nf or mati o n o n a nal ysis wi n d o ws will be 
pr o vi de d i n t he S A P. 
9. 4. 7  
S afet y a n d T oler a bilit y A n al yses 
Safet y a nal yses i ncl u de s u m maries f or A Es, p h ysical e xa mi nati o n, b o d y wei g ht, vital si g ns, 
1 2-lea d E C G, a n d safet y  la b orat or y tests.  
All A Es will be c o de 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). 
Treat me nt-e mer ge nt A Es will be ta b ulate d b y Me d D R A s yste m or ga n class a n d preferre d 
ter m. Listi n gs will als o be pr o vi de d f or A Es a n d A Es of s pecial i nterest.  
Ot her safet y meas ures will be s u m marize d descri pti vel y b y c o h ort a n d visit.  
As a t olera bilit y a nal ysis, st o ol fre q ue nc y a n d c o nsiste nc y c ollecte d o n a dail y basis 
t hr o u g h o ut t he 1 0- wee k Treat me nt Peri o d will be s u m marize d (f or Part A o nl y) o n a wee kl y 
basis (i.e., a vera ge wee kl y st o ol fre q ue nc y a n d a vera ge wee kl y st o ol c o nsiste nc y). 
9. 4. 8  
I nteri m A n al ysis 
T his is a n o pe n-la bel st u d y. N o f or mal i nter i m a nal ysis is pla n ne d f or t his st u d y. I nf or mal 
s u m maries of ke y meas ures base d o n preli mi nar y data will be perf or me d o n a n o n g oi n g 
basis.  


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 5 4 of 6 0 
1 0  
A C C E S S T O S O U R C E D A T A/ D O C U M E N T S 
T he I n vesti gat or will pr o vi de direct access t o s o urce data a n d d oc u me nts f or i n di vi d uals 
c o n d ucti n g 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 re vie w. T he 
I n vesti gat or will c o ntact t he Sp o ns or i m me diatel y if c o ntacte d b y a re g ulat or y a ge nc y a b o ut a 
site i ns pecti o n. 
T he I n vesti gat or m ust i nf or m t he st u d y patie nt t hat his/ her st u d y-relate d rec or ds ma y be 
re vie we d b y t he a b o ve i n di vi d uals wit h o ut vi olati n g t he patie nt’s pri vac y of pers o nal healt h 
i nf or mati o n i n c o m plia nce wit h Healt h I ns ura nce P orta bil it y a n d Acc o u nta bilit y Act of 1 9 9 6. 
Atte nti o n is dra w n t o t he re g ulati o ns pr o m ul gate d b y t he F D A u n der t he Free d o m of 
I nf or mati o n Act pr o vi di n g, i n part, t hat i nf or mati o n f ur nis he d t o I n vesti gat ors a n d I R Bs will 
be ke pt c o nfi de ntial b y t he F D A o nl y if mai n tai ne d i n c o nfi de nce b y t he I n vesti gat or a n d 
I R B. B y si g ni n g t his pr ot oc ol, t he I n vesti gat or affir ms t o t he S p o ns or t hat t he I n vesti gat or 
will mai ntai n, i n c o nfi de nce, i nf or mati o n f ur n is he d t o hi m or her b y t he S p o ns or a n d will 
di v ul ge s uc h i nf or mati o n t o t he I R B u n der a n a p pr o priate u n dersta n di n g of c o nfi de ntialit y 
wit h s uc h b oar d.  
1 1  
Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E 
T he S p o ns or or its desi g nee will i m ple me nt a n d mai ntai n q ualit y c o ntr ol a n d q ualit y 
ass ura nce pr oce d ures wit h writte n S O Ps t o  e ns ure t he st u d y is c o n d ucte d a n d data are 
ge nerate d, d oc u me nte d, a n d re p orte d i n c o m plia n ce wit h t he pr ot oc ol, G C P, a n d a p plica ble 
re g ulat or y re q uire me nts. 
1 1. 1  
C o n d uct of St u d y 
T his st u d y will be c o n d ucte d i n acc or da nce wit h t h e pr o visi o ns of t he Declarati o n of Helsi n ki 
a n d all re visi o ns t here of ( T o k y o 2 0 0 4), a n d i n acc or da nce wit h t he F D A C o de of Fe deral 
Re g ulati o ns ( C F R § 3 1 2. 5 0 a n d § 3 1 2. 5 6) a n d t he I nter nati o nal C o nfere nce o n Har m o nisati o n 
(I C H) E 6 G ui deli nes o n g o o d cli nical practice (I nte grate d A d den d u m t o I C H E 6( R 1): 
G ui deli ne f or G o o d Cli nical Practice I C H E 6( R 2)). S pecifi call y, t his st u d y is base d o n 
a de q uatel y perf or me d la b orat or y a n d a ni mal e x peri me ntati o n;  t he st u d y will be c o n d ucte d 
u n der a pr ot oc ol re vie we d b y a n I R B or I E C; t he st u d y will be c o n d ucte d b y scie ntificall y 
a n d me dicall y q ualifie d pers o ns; t he be nefits of t he st u d y are i n  pr o p orti o n t o t he ris ks; t he 
ri g hts a n d welfare of t he patients will be res pecte d; t he p h ysicia ns c o n d ucti n g t he st u d y d o 
n ot fi n d t he hazar ds t o o ut wei g h t he p ote ntial be nefits; a n d eac h patie nt will gi ve his or her 
writte n i nf or me d c o nse nt bef o re a n y pr ot oc ol- dri ve n tests or e val uati o ns are perf or me d. 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 5 5 of 6 0 
T he I n vesti gat or ma y n ot de vi ate fr o m t he pr ot oc ol wit h o ut a f or mal pr ot oc ol a me n d me nt 
ha vi n g bee n esta blis he d a n d a p pr o ve d b y a n a p pr o priate I R B, e xce pt w he n necessar y t o 
eli mi nate i m me diate hazar ds t o t he patie nt or w he n t he c ha n ge(s) i n v ol ve o nl y l o gistical or 
a d mi nistrati ve as pects of t he st u d y a n d are a p pr o ve d b y t he Me dical M o nit or. A n y de viati o n 
ma y res ult i n t he patie nt ha vi n g t o be wit h dr a w n fr o m t he st u d y a n d ma y re n der t hat patie nt 
n o n-e val ua ble. 
1 1. 2  
Pr ot oc ol A me n d me nts 
O nl y t he S p o ns or ma y m o dif y t h e pr ot oc ol. All a me n d me nts t h at ha ve a n i m pact o n patie nt 
ris k or t he st u d y o bjecti ves, or re q uire re visi o n of t he I C F, m ust recei ve a p pr o val fr o m t he 
I R B pri or t o t heir i m ple me ntati o n. 
1 1. 3  
M o nit ori n g of St u d y 
T he I n vesti gat or will per mit t he s ite m o nit or t o re vie w st u d y data as fre q ue ntl y as is dee me d 
necessar y t o e ns ure data are be i n g rec or de d i n a n a de q uate man ner a n d pr ot oc ol a d here nce is 
satisfact or y. M o nit ori n g visits ca n occ ur re m otel y, if necessar y. 
T he I n vesti gat or will pr o vi de access t o t he s o ur ce d oc u me nts or pr o vi de  certifie d c o pies of 
me dical rec or ds f or t he M o nit or t o verif y e C R F  e ntries. T he I n vesti gat or is e x pecte d t o 
c o o perate wit h t he S p o ns or or its desi g n ee i n e ns uri n g t he st u d y a d heres t o G C P 
re q uire me nts. 
T he I n vesti gat or ma y n ot recr u it patie nts i nt o t he st u d y u ntil t he S p o ns or or its desi g nee has 
c o n d ucte d a detaile d re vie w of t he pr ot oc ol a n d e C R Fs wit h t he site staff a n d t he site has 
bee n acti vate d u p o n t he S p o ns or’s a p pr o val. Wit h a gree me nt of t he S p o ns or, atte n da nce at a n 
i n vesti gat or meeti n g ma y f ulfill t he Site I nitiati o n re q uire me nt. 
1 2  
E T HI C S 
1 2. 1  
I nstit uti o n al Re vie w B o ar d/I n de pe n de nt Et hics C o m mittee A p pr o v al 
1 2. 1. 1  
Et hics Re vie w Pri or t o St u d y 
T he I n vesti gat or will e ns ure t hat t he pr ot oc ol  a n d c o nse nt f or m are re vie we d a n d a p pr o ve d b y 
t he a p pr o priate I R B pri or t o t he start of a n y st u d y pr oce d ures. T he I R B will be a p pr o priatel y 
c o nstit ute d a n d will perf or m its f u ncti o ns i n  acc or da nce wit h F D A re g ulati o ns, I C H G C P 
g ui deli nes, a n d l ocal re q u ire me nts as a p plica ble. 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 5 6 of 6 0 
1 2. 1. 2  
Et hics Re vie w of ot her D oc u me nts 
I n a d diti o n, t he I R B will a p pro ve all pr ot oc ol a me n d me nts (e xce pt f or s po ns or-a p pr o ve d 
l o gistical or a d mi nistrati ve c ha n ges), writte n i nf or me d c o nse nt d oc u me nts a n d d oc u me nt 
u p dates, patie nt recr uit me nt pr oc e d ures, writte n i nf or mati o n t o be pr o vi de d t o t he patie nts, 
a vaila ble safet y i nf or mati o n, i nf or mati o n a b o ut pa y me nt an d c o m pe nsati o n a vaila ble t o 
patie nts, t he I n vesti gat or’s c urric ul u m vitae a n d/ or ot her e vi de nce of q ualificati o ns, a n d a n y 
ot her d oc u me nts re q ueste d b y t he I R B a n d re g ulat or y a ut h orit y as a p plica ble. 
1 2. 2  
Writte n I nf or me d C o nse nt 
T he nat ure a n d p ur p ose of t he st u d y will be f ull y e x plai ne d t o eac h patie nt ( or t he patie nt’s 
le gall y res p o nsi ble s urr o gate). Patie nts m ust be gi ve n a m ple ti me a n d o p p ort u nit y t o i n q uire 
a b o ut details of t he trial, t o ha ve q uesti o ns a ns were d t o t heir satisfacti o n, a n d t o deci de 
w het her t o partici pate. Writte n i nf or me d c o nse nt m ust be o btai ne d fr o m eac h patie nt ( or 
g uar dia n), pri or t o a n y st u d y pr oce d ures bei n g perf or me d). 
1 3  
D A T A H A N D LI N G A N D R E C O R D K E E PI N G 
1 3. 1  
D at a Re p orti n g a n d Electr o nic D at a C a pt ure 
1 3. 1. 1  
Electr o nic C ase Re p ort F or ms (e C R Fs) 
T he I n vesti gat or will be pr o vi de d wit h e C R Fs a n d will e ns ure all data fr o m patie nt visits are 
pr o m ptl y e ntere d i nt o t he e C R Fs i n acc or da nce wit h t he s pecific i nstr ucti o ns gi ve n. T he 
I n vesti gat or m ust si g n t he e C R Fs t o verif y t he i nte grit y of t he data rec or de d. 
1 3. 1. 2  
L a b or at or y D at a 
A list of t he n or mal ra n ges f or all la b orat or y tests t o be u n derta ke n f or ms part of t he 
d oc u me ntati o n t o be c ollate d pri or t o trial st art. Me d pace Refere nce La b orat ories ( M R L) has 
bee n selecte d t o c o n d uct all tests a n d all sa m ple s will be a nal yze d at M R L. T he I n vesti gat or 
m ust mai ntai n s o urce d oc u me nts s uc h as la b orat or y re p orts a n d c o m plete hist or y a n d 
p h ysical e xa mi nati o n re p orts. 
1 3. 1. 3  
Rete nti o n of S o urce D oc u me nts 
T he I n vesti gat or m ust mai nta i n s o urce d oc u me nts s uc h as la b orat or y re p orts, E C Gs, 
c o ns ultati o n re p orts, a n d c o m plete hist or y a n d p h ysical e xa mi nati o n re p orts. 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 5 7 of 6 0 
1 3. 2  
Rete nti o n of Esse nti al D oc u me nts 
Esse ntial d oc u me nts s h o ul d be mai ntai ne d f o r at least 1 1 years base d u p o n t he S p o ns or’s 
re q uire me nts a n d ma y be re q uire d t o be mai ntai ne d l o n ger base d u p o n a p plica ble re gi o nal 
re g ulat or y re q uire me nts. T he I n vesti gat or/i nstit uti o n s h o ul d ta ke meas ures t o pre ve nt 
acci de ntal or pre mat ure destr ucti o n of t hese d o c u me nts. S h o ul d t he I n vesti gat or/i nstit uti o n 
n ot be a ble t o mai ntai n t he rec or ds f or t his peri o d of ti me, t he I n vesti gat or/i nstit uti o n m ust 
i nf or m t he S p o ns or i n writi n g, via certifie d mail, at least 9 0 da ys pri or t o t he destr ucti o n of 
a n y st u d y d oc u me nts, s o t hat t he S p o ns or has t he o pti o n, at t he S p o ns or’s e x pe nse, t o ha ve 
t he rec or ds st ore d f or a l o n ger peri o d of ti me. It is t he S p o ns or’s res p o nsi bilit y t o i nf or m t he 
I n vesti gat or or i nstit uti o n as t o w he n t hese d oc u me nts n o l o n ger nee d t o be retai ne d. 
1 4  
A D MI NI S T R A TI V E I N F O R M A TI O N 
1 4. 1  
Fi n a nci n g a n d I ns ur a nce 
Fi na nci n g a n d i ns ura nce will be a d dresse d i n a se parate a gree me nt be t wee n t he S p o ns or a n d 
t he I n vesti gat or. 
1 4. 2  
P u blic ati o n P olic y 
Ar del y x, I nc. will retai n o w ners hi p of all data. All pr o p ose d p u blicati o ns base d o n t his st u d y 
will be s u bject t o t he S p o ns or’s a p pr o val re q uire me nts. 
1 5  
R E F E R E N C E S 
E k n o ya m G, La meire N, Bars o u m R, et al. T he b ur de n of ki d ne y di sease: i m pr o vi n g gl o bal 
o utc o mes, Ki d ne y I nt 2 0 0 5; 6 6: 1 3 1 0- 1 3 1 4. 
Le wis S a n d Heat o n K. St o ol f or m scale as usef ul g ui de t o i ntesti nal tra nsit ti me, Sca n d J 
Gastr oe nter ol 1 9 9 7; 3 2: 9 2 0- 9 2 4. 
Wa hee d A A, Pe draza F, Le nz O a n d Isa k o va T. P h os p hate c o ntr ol i n e n d-sta ge re nal disease: 
barriers a n d o p p ort u nities, Ne p hr ol Dial Tra ns pla nt 2 0 1 3; 2 8: 2 9 6 1- 2 9 6 8. 
K DI G O cli nical practice g ui deli ne  f or t he dia g n osis, e val uati o n, pre ve nti o n, a n d treat me nt of 
c hr o nic ki d ne y disease- mi neral a n d b o ne di s or der ( C K D- M B D), Ki d ne y I nt 2 0 0 9; 7 6: S 1 1 3. 
D O P P S Practice M o nit or ( Dial ysis O utc o mes a n d Practice Patter ns St u d y), Ar b or Researc h 
C olla b orati ve f or Healt h, 2 0 1 8. 


Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 5 8 of 6 0 
1 6  
SI G N A T U R E S 
1 6. 1  
I n vesti g at or Si g n at ure 
I a gree t o c o n d uct t he st u d y o utli ne d a b o ve acc or di n g t o t he ter ms a n d c o n diti o ns of t he 
pr ot oc ol, G C P g ui deli nes, a n d wit h a p plica ble  re g ulat or y re q uire me nts. All i nf or mati o n 
pertai ni n g t o t he st u d y will be tr eate d i n a c o nfi de ntial ma n ner. 
 
 
 
I n vesti gat or’s Si g nat ure _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
I n vesti gat or's Pri nte d Na me:  
 
I n vesti gati o nal Site or Na me of I nstit uti o n: 
 
Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 




Ar del y x, I nc. 
Pr ot oc ol N u m ber: T E N- 0 2- 4 0 2 
E diti o n N o. 2 
2 3 Fe br uar y 2 0 2 1 
C O N FI D E N TI A L  
Pa ge 6 0 of 6 0 
A P P E N DI X I:  
U S E O F P RI O R A N D C O N C O MI T A N T M E DI C A TI O N S 
Pr o hi bite d Me dicati o ns: 
T o miti gate t he i m pact of p ossi ble GI si de effects wit h te na pa n or, t he f oll o wi n g n o n-st u d y 
me dicati o ns t hat ma y i ncrease b o wel m o ve me nt  fre q ue nc y a n d/ or l o ose n st o ol m ust be 
disc o nti n ue d bef ore starti n g te na pa n or a n d m ust be pr o hi bite d d uri n g t he st u d y:  

St o ol s ofte ner

La xati ves

Ma g nesi u m

L u brica nts
At eac h visit, patie nts will be q uesti o ne d w het her t he y are recei vi n g a n y of t hese 
me dicati o ns; if t he a ns wer is yes, patie nts wi ll be i nstr ucte d t o st o p t hese me dicati o ns.  
Rec o m me n de d Me dicati o ns f or Ma na gi n g C ha n ges i n B o wel M o ve me nts: 
F or patie nts e x perie nci n g a n i ncrease i n b o wel m o ve me nt fre q ue nc y a n d/ or l o oser st o ol after 
recei vi n g te na pa n or, t he f oll o wi n g n o n-st u d y me dicati o ns ma y be rec o m me n de d f or 
ma na gi n g t hese c ha n ges t o  b o wel m o ve me nts:  

O ver-t he-c o u nter a nti- diarr heal me dici ne (e. g., I m o di u m)
Re p orti n g of P T H- M o dif yi n g Me dicati o ns: 
T he use of P T H- m o dif yi n g me dicati o ns d uri n g t he st u d y i ncl u di n g, b ut n ot li mite d t o t he 
f oll o wi n g, will be c hec ke d wit h eac h patie nt at e ver y visit, a n d if ta ke n, be a de q uatel y 
rec or de d i n t he Pri or/ C o nco mita nt Me dicati o ns e C R F: 

Calcitri ol ( 1, 2 5- di h y dr o x yc h olecalcifer ol)

Hecter ol ( d o xercalcifer ol)

Parsa bi v (etelcalceti de)

Se nsi par (ci nacalcet)

Ze m plar ( paricalcit ol)