Clinical trial NCT03824587
Conditions: Hyperphosphatemia
Sponsor: Ardelyx
Start date: 2019-02-28; Completion date: 2019-07-17
Enrollment: 236 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized, double-blind, placebo-controlled study to evaluate the effect of tenapanor on change in s-P levels when tenapanor is administered orally, twice daily for 28 days as adjunctive therapy to ESRD subjects with hyperphosphatemia on stable phosphate binder therapy.

Detailed description:
The study consists of a Screening visit; a Run-in Period of at least 2 weeks and up to 4 weeks, where existing phosphate binder treatment is maintained; and a 4-week Double-Blind Treatment Period.

At Screening, a subject must be on thrice daily phosphate binder therapy and have a serum phosphate (s-P) level ≥5.5 and ≤10.0 mg/dL to qualify for entering the study. s-P will be measured at each visit during the run-in period to enable the evaluation of the s-P randomization criteria.

Subjects who qualify to enroll in the study will be randomized in a 1:1 ratio to receive tenapanor or placebo while continuing their existing phosphate binder treatment.

During the Double-Blind Treatment Period, subjects will receive tenapanor or placebo starting at a dose of 30 mg bid

Arms: arm 1: During the Double-Blind Treatment Period, subjects will receive tenapanor starting at a dose of 30 mg bid (three 10 mg tablets each time).

Investigators may decrease or increase the dose of study medication based on s-P levels and/or gastrointestinal (GI) tolerability in 10 mg increments to a minimum of 10 mg bid or a maximum of 30 mg bid at any time during the Double-Blind Treatment Period. arm 2: same size, weight and appearance of experimental drug
Interventions: intervention 1: Tenapanor intervention 2: Placebo intervention 3: Phosphate Binder Agents
Intervention descriptions: intervention 1: Active Drug intervention 2: Inactive Drug intervention 3: standard of care phosphate binder use at study entry was maintained throughout the entire study

Protocol documents:
Prot_SAP_000.pdf: 




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


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C O N FI D E N TI A L  
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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  ........................................................ 2 5 
7. 1  
Rec or di n g of D at a .......................................................................................... 2 5  
7. 2 
D at a C ollecti o n Pri o r t o E nr oll me nt  ............................................................ 2 5 
7. 3  
S af et y V ari a b les ............................................................................................. 2 5 
7. 3. 1 
P h ysical E x a mi nati o n  ...................................................................................... 2 6 
7. 3. 2  
Vital Si g ns ( bl o o d press ure a n d heart rate) ...................................................... 2 6  
7. 3. 3 
Electr ocar di o gra m  ............................................................................................ 2 6 
7. 3. 4 
Cli nical La b or at or y Tests ................................................................................. 2 6  
7. 3. 5 
A nal ysis of Cli nical La b orat or y Te sts ............................................................. 2 7 
7. 4  
A d verse E ve nts  ............................................................................................... 2 8 
7. 4. 1  
A d verse E v e nts Ass ociat e d wit h C ha n ge i n St o ol F or m a n d/ or 
Fre q u e nc y ......................................................................................................... 2 8  
7. 4. 2  
Rec or di n g A d verse E ve nts............................................................................... 2 8  
7. 4. 3  
Assess me nt of A d vers e E ve nts ........................................................................ 2 9  
7. 4. 4  
F oll o wi n g A d v erse E ve nts  ............................................................................... 2 9 
7. 4. 5  
Disc o nti n uati o n d ue t o A d verse E ve nts ........................................................... 3 0  
7. 4. 6 
Pre g n a nc y ......................................................................................................... 3 0  
7. 4. 7  
Seri o us A d verse E v e nts ................................................................................... 3 0  
7. 4. 8  
Re p orti n g Seri o us A d v erse E ve nts .................................................................. 3 1  
7. 5  
Effic ac y  E n d p oi nts  ......................................................................................... 3 2 
8  
M E T H O D O L O G Y/ S T U D Y VI SI T S  ................................................................... 3 2 
8. 1 
Scree ni n g Pr oce d ures: Visit 1 ( D a ys - 2 1 t o - 1 4) .......................................... 3 2 
8. 2 
R u n -i n Pr oce d ures: Visits 2 a n d 3 ( D a ys - 7 a n d - 1) ................................... 3 3 
8. 3  
Visit 4 ( D a y 1) ................................................................................................. 3 3  
8. 4  
Visits 5, 6, a n d 7 ( D a ys 8, 1 5, a n d 2 2) ........................................................... 3 4  
8. 5  
Visit 8 ( D a y 2 9) ............................................................................................... 3 4  
8. 6 
E arl y Ter mi n ati o n Visit  ................................................................................ 3 4 
8. 7 
Wit h dr a w al Pr oce d ures  ................................................................................ 3 5 
8. 8 
Criteri a f or St u d y Ter mi n ati o n  .................................................................... 3 5 
8. 9 
T ot al Bl o o d V ol u me Re q uire d f or St u d y  ..................................................... 3 5 
8. 1 0  
Pr ot oc ol D e vi ati o ns ........................................................................................ 3 6  
9  
S T A TI S TI C A L C O N SI D E R A TI O N S  ................................................................ 3 6 
9. 1 
St atistic al A n al ysis Pl a n ................................................................................ 3 6  
9. 2 
Deter mi n ati o n of S a m ple Size  ....................................................................... 3 7 
9. 3  
A n al ysis P o p ul ati o ns ...................................................................................... 3 7  
9. 4 
St atistic al Met h o ds  ......................................................................................... 3 8 
9. 4. 1  
Ge ner al C o nsi derati o ns .................................................................................... 3 8  
9. 4. 2 
Baseli ne Descri pti ve Statistics  ......................................................................... 3 8 
9. 4. 3 
Pri mar y Efficac y A nal ysis  ............................................................................... 3 8 
9. 4. 4 
Sec o n dar y Efficac y A nal ys es  .......................................................................... 3 9 
9. 4. 5 
M ulti ple C o m paris o ns / M ulti plicit y  ............................................................... 3 9 
9. 4. 6  
Ha n dli n g of Missi n g Dat a ................................................................................ 4 0  
9. 4. 7  
A dj ust me nts f or C o variat es ............................................................................. 4 1  
9. 4. 8 
Visit Wi n d o ws  ................................................................................................. 4 1 


Ar del y x, I nc.  
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E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 4 
9. 4. 9  
Safet y A nal yses ................................................................................................ 4 1  
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  ................................................. 4 1 
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  .................................. 4 2 
1 1. 1 
C o n d uct of St u d y  ........................................................................................... 4 2 
1 1. 2 
Pr ot oc ol A me n d me nts  ................................................................................... 4 2 
1 1. 3  
M o nit ori n g of St u d y....................................................................................... 4 3  
1 2  
E T HI C S  ................................................................................................................. 4 3 
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 ......................................................................................................... 4 3  
1 2. 1. 1 
Et hics Re vie w Pri or t o St u d y  ........................................................................... 4 3 
1 2. 1. 2  
Et hics Re vie w of ot her D oc u me nts ................................................................. 4 3  
1 2. 2  
Writte n I nf or me d C o nse nt  ............................................................................ 4 3 
1 3  
D at a  H A N D LI N G  A N D R E C O R D K E E PI N G  ................................................... 4 4 
1 3. 1  
D at a Re p orti n g a n d Electr o nic D at a C a pt ure ............................................ 4 4  
1 3. 1. 1 
Electr o nic Case Re p ort F or ms (e C R Fs) ........................................................... 4 4 
1 3. 1. 2 
La b orat or y D ata  ............................................................................................... 4 4 
1 3. 1. 3  
Rete nti o n of S o urce D oc u me nts ...................................................................... 4 4  
1 3. 2  
Rete nti o n  of Esse nti al D oc u me nts  ................................................................ 4 4 
1 4  
A D MI NI S T R A TI V E I N F O R M A TI O N  .............................................................. 4 5 
1 4. 1 
Fi n a nci n g a n d I ns ur a nce  ............................................................................... 4 5 
1 4. 2 
P u blic ati o n P olic y  .......................................................................................... 4 5 
1 5  
R E F E R E N C E S  ...................................................................................................... 4 5 
1 6  
SI G N A T U R E S  ....................................................................................................... 4 6 
1 6. 1  
I n vesti g at or Si g n at ure ................................................................................... 4 6 
1 6. 2  
S p o ns or Si g n at ure  .......................................................................................... 4 7 
 
I n-te xt Fi g ures 
Fi g ure 4 - 1: 
St u d y Desi g n Dia gr a m  ..................................................................................... 1 8 
I n-te xt T a bles 
Ta ble 7 - 1: 
Cli nical La b or at or y Tests ................................................................................. 2 7  
Ta ble 8 - 1: 
A p pr o xi mate Bl o o d V ol u me per S u bject......................................................... 3 5  
 
 




Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 6 
1. 2  
S y n o psis  
P r ot oc ol Title:  
A ra n d o mize d, d o u ble -bli n d , place b o -c o ntr olle d st u d y t o e val uate t he 
efficac y of te na pa n or as a dj u ncti ve t hera p y t o p h os p hate bi n der t hera p y i n 
e n d-sta ge re nal disease ( E S R D) s u bjects wit h h y per p h os p hate mia  
S p o ns or:  
Ar del y x, I nc.  
St u d y P h ase:  
P hase 2/ 3  
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  o n c ha n ge i n ser u m p h os p h or us 
(s-P) le vels w he n te na pa n or is a d mi nistere d orall y, t wice dail y f or 
2 8 da ys as a dj u ncti ve t hera p y t o E S R D s u bj ects wit h 
h y per p h os p hate mia o n sta ble p h os p hate bi n der t hera p y. 
T he sec o n dar y o bj ecti ves of t his st u d y are:  
•  
T o e val uate t he effect of  te na pa n or vers us place b o as a dj u ncti ve 
t hera p y wit h p h os p hate bi n der t o l o wer s u bject’s s- P le vel t o 
< 5. 5 m g/ d L.  
•  
T o e val uate t he effect of te na pa n or vers us place b o as a dj u ncti ve 
t hera p y wit h p h os p hate bi n der 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 c- ter mi nal fi br o blast gr o wt h fact or 2 3 (c F G F 2 3). 
•  
T o e val uate t he effect of te na pa n or vers us place b o as a dj u ncti ve 
t hera p y wit h p h os p hate bi n der o n parat h yr oi d h or m o ne ( P T H). 
T he e x pl orat or y o bj ecti ve of t his st u d y is:  
•  
T o c ollect a n d st ore plas ma/ser u m f or f ut ure e x pl orat or y  researc h i nt o 
ser u m/ plas ma bi o mar kers relate d t o car di ore nal disease a n d/ or b o ne 
meta b olis m or t hat ma y i nfl ue nce t he res p o nse (i.e. distri b uti o n, 
safet y, t olera bilit y, a n d efficac y) t o te na pa n or. T hese data will n ot be 
part of t he cli nical st u d y re p ort. 
N u m ber of Sites:  
4 0  t o 5 0  
St u d y Desi g n:  
T his is a ra n d o mize d, d o u ble -bli n d , place b o -c o ntr olle d st u d y t o e val uate 
t he effect of te na pa n or o n c ha n ge i n s- P le vels w he n te na pa n or is 
a d mi nistere d orall y, t wice dail y f or 2 8 da ys as a dj u ncti ve t hera p y t o E S R D 
s u bj ects wit h h y per p h os p hate mia o n sta ble 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 visit ; a R u n -i n Peri o d of at least 2 wee ks  
a n d u p t o 4 wee ks, w he re e xisti n g p h os p hate bi n der treat me nt is 
mai ntai ne d ; a n d a 4- wee k D o u ble- Bli n d  Treat me nt  Peri o d , d uri n g w hic h 
s u bj ects are ra n d o mize d i n a 1: 1 rati o t o recei ve te na pa n or or place b o 
treat me nt w hile c o nti n ui n g t heir e xisti n g p h os p hate bi n der treat me nt. T he 
d ose of p h os p hate bi n der s h o ul d re mai n u nc ha n ge d t hr o u g h o ut t he st u d y 
(fr o m Scree ni n g t o t he e n d of st u d y) 
T he Scree ni n g visit ( Visit 1) 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 s u bjects 
o n a M o n da y -W e d nes da y-F ri da y sc he d ule a n d T h urs da y or Sat ur da y f or 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 7 
s u bj ects o n a Tues da y -T h urs da y -S at 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 o rme d 
pre- dial ysis . All ot her assess me nts ma y be perf o rme 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.  
At Scree ni n g  ( Visit 1), a s u bj ect m ust be o n t hrice dail y p h os p hate bi n der 
t hera p y a n d ha ve a s- P le vel ≥5. 5 a n d ≤1 0. 0 m g/ d L t o q ualif y f or e nteri n g 
t he st u d y. T he s u bject s h o ul d be t ol d t o c o nti n ue t heir e xisti n g p h os p hate 
bi n der treat me nt t hr o u g h o ut t he st u d y wit h o ut a n y c ha n ge t o t he p h os p hate 
bi n der d ose. Ser u m p h os p h or us will be meas ure d at eac h visit  ( pre-dial ysis 
after a s h ort i nter val) d uri n g t he R u n -i n Peri o d t o e na ble t he e val uati o n of 
t he s- P ra n d o mizati o n criteria. T o be ra n d o mize d at Visi t 4 ( Da y 1), 
s u bj ects m ust ha ve a s- P le vel ≥5. 5 a n d ≤1 0. 0 m g/ d L  at Visit 3.  
S u bj ects w h o d o n ot meet t he ra n d o mizati o n criteria base d o n t he s-P le vel 
at Visit 3  will be disc o nti n ue d  as scree n fail ures . S u bjects 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 ra n d omizati o n . 
T h ose s u bjects w h o meet t he s- P criteria at Scree ni n g ( Visit 1 ), b ut scree n 
fail d ue t o t he s- P le vel at Visit 3 ca n be re-scree ne d; t he y m ust wait a 
mi ni m u m of o ne wee k after scree n faili n g t o be re -scree ne d. 
D uri n g t he D o u ble- Bli n d  Treat me nt Pe ri o d, su bject s will recei ve te na pa n or 
or place b o starti n g at a d ose of 3 0 m g t wice dail y (bi d; t hree 1 0 m g ta blets 
eac h ti me ). T e na pa n or or place b o  will be ta ke n t wice dail y; j ust pri or t o 
brea kfast a n d di n ner. S u bject s s h o ul d n ot  ta ke st u d y me dicati o n  at t he 
meal i m me diatel y prece di n g dial ysis.  
I n vesti gat ors ma y decrease or i ncrease t he d ose of st u d y me dicati o n base d 
o n s- P le vels a n d/ or gastr oi ntesti nal ( GI ) t olera bilit y i n 1 0 m g i ncre me nts 
t o a mi ni m u m of 1 0 m g bi d or a ma xi m u m of 3 0 m g bi d after 
Ra n d o m izati o n ( Visit 4) t o Da y 1 5 ( Visit 6). D oses ca n be a dj uste d 
bet wee n visits.  
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 d verse 
e ve nt  ( A E) rec or di n g. 
Bl o o d sa m ples will be c ollecte d a n d 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.  
Pl a n ne d S a m ple Size:  
A p pr o xi matel y 2 1 4  E S R D  s u bj ects will be ra n d o mize d  i n t his st u d y. 
S u bject Selecti o n 
Criteri a:  
I ncl usi o n C riteri a: 
1.  
Si g ne d a n d date d i nf or me d c o nse nt 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, n o n-lactati n g a n d f ulfilli n g o ne of 
t he f oll o wi n g: 
 
 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 8 
a. P ost -me n o pa usal defi ne d as a me n orr hea f or at least 
1 2 m o nt hs f oll o wi n g cessati o n of all e x o ge n o us h or m o nal 
treat me nts a n d wit h f ollicle sti m ulati n g h or m o ne ( F S H) 
le vels i n t he la b orat or y defi ne d p ost- me n o pa usal ra n ge. 
b.  D oc u me nta ti o n of irre versi ble s ur gical sterilizati o n b y 
h ysterect o m y, bilateral o o p h orect o m y or bilateral 
sal pi n gect o m y b ut n ot t u bal li gati o n. 
c. Use of acce pta ble c o ntrace pti ve met h o d: i ntra uteri ne 
de vice (I U D) wit h s per mici de, a fe male c o n d o m wit h 
s per mici de, c o ntrace pti ve s p o n ge wit h s per mici de, a n 
i ntra va gi nal s yste m (e. g., N u va Ri n g® ), a dia p hra g m wit h 
s per mici de, a cer vical ca p wit h s per mici de, or oral, 
i m pla nta ble, tra ns der mal, or i njecta ble c o ntrace pti ves, 
se x ual a bsti ne nce, or a sterile se x ual part ner fr o m 
Scr ee ni n g ( Visit 1) u ntil 3 0 da ys after t he last s u bject visit . 
4.  
Males m ust a gree t o a v oi d fat heri n g a c hil d ( or d o nati n g s per m), 
a n d t heref ore be eit her sterile ( d oc u me nte d) or a gree t o use, fr o m 
t he ti me of e nr oll me nt u ntil 3 0  da ys after e n d of st u d y, o ne of t he 
f oll o wi n g a p pr o ve d met h o ds of c o ntrace pti o n: a male c o n d o m wit h 
s per mici de, a sterile se x ual part ner, use of a n I U D wit h s per mici de 
b y fe male se x ual part ner, a fe male c o n d o m wit h s per mici de, 
c o ntrace pti ve s p o n ge wit h s per mici de, a n i ntra va gi nal s yste m  
(e. g., N u va Ri n g ® ), a dia p hra g m wit h s per mici de, a cer vical ca p 
wit h s per mici de, or oral, i m pla nta ble, tra ns der mal, or i nj ecta ble 
c o ntrace pti ves. 
5.  
C hr o nic mai nte na nce he m o dial ysis ( H D) 3 x/ 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 
s u bj ect 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.  
6.  
If recei vi n g acti ve vita mi n D or calci mi metics, t he d ose s h o ul d 
ha ve bee n u nc ha n ge d f or t he last 4 wee ks pri or t o S cree ni n g 
( Visit 1) . 
7.  
Kt/ V ≥1. 2 at m ost rece nt meas ure me nt pri or t o Scree ni n g ( Visit 1). 
8.  
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 . T he prescri be d d ose s h o ul d ha ve bee n u nc ha n ge d d uri n g 
t he last 4 wee ks pri or t o Scree ni n g ( Visit 1) . 
9.  
Ser u m p h os p h or us le vels m ust be ≥5. 5  a n d ≤1 0. 0 m g/ d L at 
S cree ni n g ( Visit 1) a n d t he e n d of t he R u n-i n Peri o d ( Visit 3), 
a nal yze d at t he ce ntral la b orat or y use d i n t he st u d y.  
1 0.  
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. 
 
 
 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 9 
E xcl usi o n C riteri 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 o n p h os p hate- bi n ders 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 S cree ni n g 
( Visit 1). 
2.  
Ser u m/ plas ma parat h yr oi d h or m o ne > 1 2 0 0 p g/ m L. T he m ost rece nt 
val ue fr o m t he s u bject’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 In vesti gat or . 
4.  
Hist or y of i nfla m mat or y b o wel disease (I B D) or irrita ble b o wel 
s y n dr o me wit h diarr hea (I B S-D).  
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 peri o d.  
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 s u bject 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 Me dic ati o n : 
T e na p a n or 1 0 m g ta blets or  matc he d place b o  ta blets 
S af et y a n d Effic ac y  
Me as ures : 
S af et y M e as ures : 
P h ysical e xa mi nati o n; b o d y wei g ht; vital si g ns; 1 2 -lead E C G; 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 ); a n d A E 
m o nit ori n g. 
Effic ac y  Me as ures: 
Ser u m p h os p h or us, i F G F 2 3, c F G F 2 3, a n d P T H. 
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 be c o m prise d of all 
ra n d o mize d s u bjects.  
•  
F ull A n al ysis Set  ( F A S): will i ncl u de all I T T  s u bjects w h o ha ve at 
least o ne p ost- ba seli 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  t o be perf or me d wit h 
s u bj ects as ra n d o mize d.  
•  
P er -P r ot oc ol P o p ul ati o n: will be a s u bset of t he F A S . It will be 
t he a nal ysis p o p ulati o n f or se nsiti vit y a nal ysis t o be perf or me d 
wit h s u bjects as ra n d o mize d. A n y s u bj ect w h o has a si g nifica nt 
pr ot oc ol de viati o n t hat c o ul d alter his/ her efficac y o utc o me t o 
treat me nt will be e xcl u de d fr o m t he P P p o p ulati o n.  
 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 1 0  
•  
Wee k 4 C o m pleters:  will be a s u bset of t he F A S . It will i ncl u de 
all F A S s u bjects w h o c o m plete  t he s-P assess me nt at Wee k 4 . It 
will be t he a nal ysis p o p ulati o n f or se nsiti vit y a nal ysis t o be 
perf or me d wit h s u bjects as ra n d o mize d .  
•  
S af et y P o p ul ati o n:  will i ncl u de all I T T  s u bjects w h o recei ve at 
least o ne d ose of st u d y me dicati o n (te na pa n or or place b o). It will 
be t he a nal ysis p o p ulati o n f or safet y a nal yses t o be perf or me d wit h 
s u bj ects as treate d.  
S af et y A n al yses:  
All safet y meas ures will be s u m marize d descri pti vel y . A Es will be 
s u m marize d b y Me d D R A s yste m or ga n class a n d preferre d ter m . 
Effic ac y  An al yses:  
T he pri mar y efficac y e n d p oi nt is t he c ha n ge fr o m baseli ne i n s -P le vel at 
Wee k 4 . F or t his c o nti n u o us e n d p oi nt, t he f oll o wi n g pair of h y p ot heses 
will be teste d : 
H 0: µt = µ p 
vers us  
H 1: µt ≠ µ p 
w here µ t a n d µp de n ote t he mea n c ha n ges fr o m baseli ne i n s -P le vel at 
Wee k 4 i n t he te na pa n or a n d place b o gr o u ps, res pecti vel y. As  t he pri mar y 
a nal ysis, the treat me nt c o m paris o n of t he mea n c ha n ge will be perf or me d  
usi n g a mi xe d -effects  m o del f or re peate d meas ures  ( M M R M) o n o bser ve d 
cases of t he F A S . T he M M R M  will i ncl u de  t y pe of p h os p hate bi n der 
(se vela mer or n o n-se vela mer), s-P le vel at Visit 3 ( < 7. 5 m g/ d L or 
≥7. 5 m g/ d L), treat me nt, visit ( Wee k 1 t hr o u g h Wee k 4), treat me nt-b y -visit 
i nteracti o n as fi xe d effects; baseli ne ( Visit 4) s-P le vel  a n d baseli ne- b y-
visit as c o variates;  a n d s u bject as a ra n d o m effect . A n u nstr uct ure d 
c o varia nce matri x will b e use d t o m o del t he wit hi n-s u bject err ors.  
T he M M R M a p pr oac h will als o be a p plie d t o t he a nal ysis of c ha n ges fr o m 
baseli ne i n s -P at Wee k 1, Wee k 2, a n d Wee k 3 . A n a nal ysis of varia nce 
( or c o varia nce) will be perf or me d f or i F G F 2 3/c F G F 2 3 ( or P T H) e n d p oi nts.  
F or bi nar y res p o nse e n d p oi nts, t he res p o nse rate defi ne d as t he pr o p orti o n 
of s u bjects reac hi n g a n s- P le vel < 5.5 m g/ dl will be esti mate d at eac h p ost-
baseli ne visit a n d c o m pare d bet wee n treat me nt gr o u ps. 
 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 1 1  
1. 3  
Sc he d ule of Assess me nts a n d Pr oce d ures  
 
Scree ni n g  
R u n -i n 
Peri o d  
Tre at me nt  
Peri o d  
Visit 1  
Visit 2  
Visit 3  
Visit 4  
Visit 5  
Visit 6  
Visit 7  
Visit 8/ E T  
We e k -4 t o -3  
We e k -2  
We e k -1  
D a y 1  
We e k 1  
We e k 2  
We e k 3  
We e k 4  
Visit Wi n d o w  
-3 0  t o - 1 4d 
-1 8  t o -7  
( 5-1 6  d a ys 
after V 1 ) 
-9 t o -2  
( 5-9 d a ys 
after V 2 ) 
1 e 
( 2-9 d a ys 
after V 3)  
8 ± 2  
1 5  ± 2  
2 2  ± 2  
2 9  ± 2  
St u d y Pr oc e d ur e  
 
I nf or me d Co nse nt  
X  
 
 
 
 
 
 
 
I ncl usi o n/ 
E xcl usi o n C riteria 
X  
 
 
X f 
 
 
 
 
De m o gra p hics  
X  
 
 
 
 
 
 
 
Me dical / S ur gical H ist or y  
X  
 
 
X g  
 
 
 
 
Pri or/ C o n M e ds 
X  
X  
X  
X  
X  
X  
X  
X  
P h ysica l Exa mi nati o n  
X  
 
 
 
 
 
 
X  
Wei g ht ( pre -dial ysis ) 
X  
 
 
 
 
 
 
X  
Hei g ht  
X  
 
 
 
 
 
 
 
Vital S i g nsa, 
X 
 
 
X 
 
 
 
X 
1 2 -lea d E C G 
X  
 
 
 
 
 
 
X  
Safet y La b orat or y E val u ati o ns b 
X  
 
 
 
 
 
 
X  
Ser u m P h os p h or us  
X  
X * 
X  
X  
X  
X  
X  
X  
F S H T est c 
X  
 
 
 
 
 
 
 
Pre g na nc y T est c 
X  
 
 
 
 
 
 
X  
Ra n d o mizati o n  
 
 
 
X  
 
 
 
 
S t u d y Me dicati o n  
Dis pe nse a n d/ or R et ur n 
 
 
 
X 
X 
X 
X 
X 
F G F 2 3 a n d P T H Bl o o d S a m ple 
 
 
 
X  
 
 
 
X  
Bi o mar ker Bl o o d S a m ple  
 
 
 
X 
 
 
 
X 
A E A ss ess me nt 
 
X  
X  
X  
X  
X  
X  
X  
* At Visit 2, a ser u m p h os p h or us le vel of < 5. 5 m g/ d L or > 1 0. 0 m g/ d L d oes n ot dee m t he s u bj ect i neli g i ble. H o we ver, t he 
s u bj ect ma y be disc o nti n ue d at t he I n vesti gat or’s discreti o n.  
a  Vital si g ns i ncl u de sitti n g or s u pi ne bl o o d press ure a n d p uls e, pri or t o dial ysis . 
b  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 ot her t ha n t he ser u m p h os p h or us 
test liste d i n T a ble 7 - 1. 
c  F S H ( p ost me n o pa usal fe males)  a n d p re 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 steriliz ati o n, or F S H test c o nfir ms p ost -me n o pa usal stat us.  
d  Scree ni n g ( Visit 1) c o ul d be 1 4 t o 3 0 da ys (i.e. 2 t o 4 wee ks) bef ore ra n d o mizati o n f oll o wi n g t he s h ort -i nter val sc he d ule.  
e  Da y 1 is t he ra n d o mizati o n da y a n d ser ves as t he refere nce da y f or all visits.  
f  S u bj ects 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, i ncl u di n g t he criteria 
b ase d o n t he s -P le vel at Visit 3 . 
g  Rec or d o nl y c ha n ges t o me dic al hist or y fr o m Visit 1  


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 1 2  
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 N C O V A  
a nal ysis of c o varia nce  
A N O V A  
a nal ysis of varia nce  
A S T  
as partate a mi n otra nsa mi nase  
bi d  ( b.i. d.) 
bis e n die, t wice a da y  
B U N  
bl o o d urea nitr o ge n  
c F G F 2 3  
c-ter mi nal fi br o blast gr o wt h fact or 2 3 
C F R  
C o de of Fe deral Re g ulati o ns ( U nite d States)  
CI  
co nfi de nce i nter val  
C K D  
c hr o nic ki d ne y disease  
C R O  
co 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 S R D  
e n d -sta ge re nal disease 
F A S  
F ull A nal ysis Set  
F D A  
( Uni te d S tates) 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 D 
irrita ble b o wel disease 
I B S 
irrita ble b o wel s y n dr o me  
I B S- C 
irrita ble b o wel s y n dr o me wit h c o nsti pati o n  
I B S- D 
irrita ble b o wel s y n dr o me wit h diarr hea  
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 H ar m o nizati o n 
I E C 
I n de pe n de nt Et hics C o m mitte e 
i F G F 2 3 
i ntact fi br o blast gr o wt h fact or 2 3 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 1 3  
A b bre vi ati o n  
Defi niti o n  
I R B 
I nstit uti o nal Re vie w B oar d 
I R T 
I nteracti ve Res p o nse T ec 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  
L O C F  
last-o bser vati o n -carrie d -f or war d 
Me d D R A  
Me dical Dicti o nar y f or Dr u g Re g ulat or y Acti vities  
M M R M  
mi xe d -effects f or re peate d me as ures  
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 P  
P er -Pr ot oc ol  
P T H  
parat h yr oi d h or m o ne  
p- val ue  
pr o ba bilit y val ue  
Q R S  
pri nci pal deflecti o n i n E C G  
Q T  
E C G i nter val  
Q T c 
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  
T E A E  
treat me nt-e mer ge nt a d verse e ve nt  
ti d ( or t.i. d.) 
ter i n die, t hree ti mes a da y 
U N  
u nstr uct ure d  
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 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 1 4  
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) aff ects 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 n al 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 n cti o n, t he a bilit y of t he ki d ne ys t o a p pr o priatel y e x crete 
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 vers al c o m plicati o n of E S R D . 
H y p er 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 cir c 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 ntreat e d, h y per p h os p hate mia ca n lea d t o vas c ular a n d tiss ue calcificati o ns, b o ne pai n, 
fract ur es, a n d w orse ni n g sec o n dar y h y p er p arat h yr oi dis m a n d is ass ociate d wit h i ncrease d 
car di o vas c ular m or bi dit y a n d m ortalit y. O bs er vati o nal d ata 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 h ate 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 ), a n d a meta-a nal ysis of ra n d o mize d cli nical trials de m o nstrate t hat 
n o n- calci u m -b ase d bi n ders ha ve a l o w er m ortalit y as c o m pare d t o calci u m- base d bi n ders 
(J a mal et al i n t he La n cet, p u blis he d o nli ne 1 9 J ul y 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 x cess 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 ut e t o ot her e mer gi n g c hr o nic ki d ne y 
disease -s pecific mec ha nis ms of car di o vas c ular t o xicit y (Wa hee d 2 0 1 3 ). H e 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. H o w e ver, a lar ge 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 h or us c o ntr ol ( D O P P S Practice M o nit or 2 0 1 8 ). A n i m p orta nt 
barrier f or a s u ccessf ul tr eat me nt is t he pill b ur de n ass ociate d wit h all p h os p hate bi n ders, 
w hic h ha ve t o be d os e d i n se veral gr a ms per d a y a n d ta ke n wit h eac h meal t o bi n d dietar y 
p h os p h or us. T he si de eff ect pr ofile wit h p o or gastr oi ntesti nal ( GI) t olera bilit y a n d c o n cer 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 -b ase d bi n d ers, res p ecti vel y, f urt h er i m pair a n 
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 rati o nale t o de vel o p oral 
p h os p hate- l o weri n g me di cati o n s wit h ne w mec h a nis ms of acti o n, a m ore c o n ve nie nt d osi n g, 
a n d i m pr o ve d ris k- be n efit pr ofile.  


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 1 5  
Te na pa n or is a n oral, mi ni mall y a bs or b e d c o m p o u n d t hat i n hi bits t he s o di u m- h y dr o ge n 
e x c ha n ger 3 ( N H E 3 ) tr a ns p orter l ocall y i n t he GI  tract, w hic h lea ds t o re d u ce d s o di u m a n d 
fl ui d a bs or pti o n. Data fr o m pre -cli nical st u dies a n d res ults i n healt h y v ol u nteers s h o w t hat 
te na pa n or als o re d uces t h e u pta ke of p h os p h or us fr o m t he g ut.  
Te na pa n or re d u ces i ntesti nal p h os p hate a bs or 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 her e b y re d uci n g p aracell ular p h os p hate p er mea bilit y; t his effect is 
me diate d e x cl usi vel y via o n -tar get N H E 3 i n hi biti o n.  
Te na pa n or has bee n a d mi nistere d t o a p pr o xi matel y 3 4 7 healt h y s u bjects at si n gle d oses u p t o 
9 0 0 m g, a n d i n r e peat e d d oses u p t o 1 8 0 m g/ da y f or 7 da ys; t o a p pr o xi matel y 1 0 2 0 s ubject s 
wit h irrita ble b o wel s y n dr o me wit h c o nsti pati o n (I B S-C) , at d oses u p t o 1 0 0 m g/ da y f or u p t o 
1 2 wee ks; a n d t o 4 7 7 C K D s u bjects ( C K D Sta ges 3 B , 4, a n d 5 D) f or u p t o 1 2 wee ks at d oses 
u p t o 1 2 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 o c hl ori de salt a n d is c he micall y d escri b e d as: ( S)-N, N’ -( 1 0, 1 7- di o x o- 3, 6, 2 1, 2 4-
tetra o x a- 9, 1 1, 1 6, 1 8-tetraaza he x ac 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 n es 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 yell o w, o v al bic o n ve x fil m- c oate d ta blets  
 
 
 
D osi n g c o nsists of o ne t o t hree 1 0 m g ta blets, ta ke n t wice dail y j ust 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 dial ysis).  
Te na pa n or ta blets ( 1 0 m g, a d mi nistere d as 1 0. 6 m g of t he h y dr oc hl ori de salt) are p ac ka ge d i n 
a n o pa q ue w hite hi g h -d e nsit y p ol yet h yl e ne (H D P E ) b ottle ( 6 0/ b ottle) wit h a w hite 
p ol y pr o p yle n e c hil d resista nt cl os ure a n d i n d ucti o n seal pl us a desicca nt ca nist er. Ta blets of 
te na pa n or s h o ul d be st or e d i n t he ori gi n al pac k a gi n g acc or di n g t o t he la b eli n g. 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 1 6  
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 v al uate d f or its a bilit y t o l o wer s- P le vels i n 
C K D  s u bjects o n dial ysis wit h h y per p h os p hate mia. Most E S R D s u bjects 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 u ate p h os p h ate c o ntr ol ( D O P P S Practice M o nit or 2 0 1 8). Si nce te na pa n or l o wers 
s- P le vels via a differe nt mec ha nis m of acti o n, it is belie ve d t hat a dj u va nt t hera p y of 
te na pa n or 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 hate-l o weri n g 
acti vit y. I n rats, te na p a n or d ose d wit h se vela mer car b o nate (a p h os p hate bi n der) si g nifica ntl y 
i ncreas e d t he a m o u nt of p h os p h or us i n t he feces as c o m pare d t o a d mi nistrati o n of se vela mer 
car b o nat e al o ne; t he i ncr ease i n f ecal p h os p h or us is a n i n vi v o p har mac o d y na mic effect of 
p h os p hate l o weri n g t her a pies. 
2. 4  
Ris k -Be nefit Assess me nt  
T he ris k-be n efit assess m e 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 1 9 cli nical trials c o n d ucte d wit h te na pa n or . R es ults fr o m t he 
ris k-be nefit ass ess me nt  are descri be d i n t he I n v esti gat or’s Br oc h ure (I B). 
N o n cli 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 hea 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 x a 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 rec o ver y p eri 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-Da wle y rats was ne gati ve.  
T he safet y, t olera bilit y, p har mac o d y n a mics a n d efficac y of te na p a n or ha v e bee n e v al uate d i n 
3 4 7 healt h y s u bjects at si n gle d oses u p t o 9 0 0 m g, a n d i n re peate d d oses u p t o 1 8 0 m g/ da y 
f or 7 da ys; t o 1 0 2 0 I B S-C s u bjects at d oses u p  t o 1 0 0 m g/ da y f or u p t o 1 2 wee ks; a n d t o 
4 7 7 C K D s u bjects ( C K D Sta ges 3 B , 4, a n d 5 D) f or u p t o 1 2 wee ks at d os es u p t o 
1 2 0 m g/ da y.  
Te na pa n o r has mi ni mal s yste mic bi oa v aila 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 bl e 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 n tifia ble 
te na pa n or w er e bel o w 1. 5 n g/ m L.    
T he re d u cti 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 h a nis m  of acti o n, te na p a n or has t he p ote ntial t o pr o d uce s ofter or  
l o oser st o ols a n d i ncreas e st o ol fre q ue n c y. Te n a p a n or has bee n de m o nstrat e d t o be ge nerall y 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 1 7  
safe a n d well t olerate d i n cli nical st u dies. T he safet y pr ofile wit h s ofte 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 v e bee n c o nsiste nt wit h its p har mac ol o g y.  
T he t he oret ical A Es  fr o m te na pa n or treat me nt i n E S R D s u bjects w o ul d be d ue t o e x a g gerate d 
p har mac ol o gical eff ects a n d ma y i ncl u de el ectr ol yt e dist ur ba n ces, meta b olic aci d osis, s oft 
st o ols/ diarr hea, a n d r e d u ce 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 ool 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 
s u bjects, se nsiti ve s u bjects s h o ul d be m o nit ore d f or si g ns of d e h y drati o n i n case of pr ol o n ge d 
se vere di arr h ea. 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 st u d y s u bject will be c hec k e d at eac h visit . All s u bjects 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 d etails o n n o n-clinical a n d cli nical res ults wit h te na pa n or.  
S u bject s 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 p ects bef ore t a ki n g p art 
i n a n y st u d y-s p ecific e x a mi nati o n. T he st u d y will be c o n d ucte d u n d er 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 w ar 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 s h ort-ter m st u d y are c o nsi dere d acce pta bl e. Res ults 
fr o m t his st u d y will be i m p orta nt f or t he de v el o p me nt of a p ote ntial ne w dr u g, w hic h c o ul d 
i mpr o ve t he treat me nt of h y per p h os p hate mia i n E S R D s u bjects. 
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 o e val uate t he eff ect of te na pa n or o n c ha n ge i n s- P le vels w he n te na p a n or is 
a d mi nistere d orall y t wice dail y f or 2 8 da ys as a dj u ncti ve t hera p y t o E S R D s u bjects 
wit h h y per p h os p hate mia o n sta ble p h os p hate bi n d er t hera p y. 
3. 2  
Sec o n d ar y O bjecti ve  
•  T o e val uate t he eff ect of te na pa n or v ers us place b o as a dj u ncti ve t hera p y wit h 
p h os p hate bi n der t o l o wer s u bject’s s- P le vel t o < 5. 5 m g/ d L. 
•  T o e val uate t he eff ect of te na pa n or v er s us place b o as a dj u ncti ve t hera p y wit h 
p h os p hate bi n der 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 c- ter mi nal 
fi br o blast gr o wt h fact or 2 3 (c F G F 2 3). 
•  T o e val uate t he eff ect of te na pa n or v ers us place b o as a dj u ncti ve t hera p y wit h 
p h os p hate bi n der o n parat h yr oi d h or m o ne ( P T H). 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 1 8  
3. 3  
E x pl or at or y O bjecti ve  
•  T o c ollect a n d st ore pl as ma/ser u m f or f ut ure e x pl orat or y res earc h i nt o ser u m/ plas ma 
bi o mar kers r elate d t o car di ore nal disease a n d/ or b o ne meta b olis m or t hat ma y 
i nfl ue nce t he res p o nse (i. e. distri b uti o n, safet y, t ol era bilit y, a n d efficac y) t o 
te na pa n or. T h ese dat a will n ot be part of t he cli nical st u d y re p ort. 
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, d o u ble- bli n d, place b o -c o ntr olle d st u d y t o e val uat e t he effi cac y of 
te na pa n or as a dj u ncti ve t hera p y t o p h os p hate bi n d er  t hera p y i n E S R D s u bjects wit h 
h y per p h os p hate mia. 
T he st u d y c o nsists of a Scree ni n g visit ; a R u n-i n Peri o d of at least 2 wee ks  a n d u p t o 
4 wee ks , w h ere e xisti n g p h os p hate bi n der treat me nt is mai ntai ne d; a n d a 4-wee k 
D o u ble- Bli n d  Tr eat me nt P eri o d, d uri n g w hi c h s u bjects are ra n d o mize d i n a 1: 1 rati o t o 
recei ve te na p a n or or place b o at a d ose of 3 0 m g t wice dail y ( bi d; t hree 1 0 m g ta blets eac h 
ti me) w hile c o nti n ui n g t h eir e xisti n g p h os p hate bi n der treat me nt. T he d ose of p h os p hate 
bi n der s h o ul d re mai n u nc ha n ge d t hr o u g h o ut t he st u d y (fr o m Scree ni n g t o t he e n d of st u d y). 
A p pr o xi matel y 2 1 4 s u bj ects will be ra n d o mize d at 4 0 t o 5 0 sites.  
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 da y an d ser ves as t he refere nce  da y f or all visits.  
 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 1 9  
T he Scree ni n g visit ( Visit 1) 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 n es da y or Fri da y f or s u bj ects o n a M o n da y- We d nes d a y- Fri da y 
sc he d ule a n d T h urs da y or Sat urda y f or s u bj ects o n a Tues da y- T h urs da y- S at ur da y sc h e 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 ass ess me nts m ust  b e 
perf or me d pre -di al ysis . All ot her assess me nts ma y be p erf or me d pre -, d uri n g, or p ost-di al ysis 
b ut s h o ul d be perf or me d at t he sa me ti me at eac h visit.  
At Scree ni n g, a s u bject m ust be o n t hrice dail y p h os p hate bi n der t hera p y a n d ha ve a s- P le vel 
≥5. 5 a n d ≤1 0. 0 m g/ d L t o q ualif y f or e nteri n g t he st u d y. T he s u bject s h o ul d be t ol d t o 
c o nti n ue t heir e xisti n g p h os p hate bi n der treat me nt t hr o u g h o ut t he st u d y wit h o ut a n y c ha n ge 
t o t he p h os p hate bi n der d ose. Ser u m p h os p h or us will be meas ure d at eac h visit  ( pre-dial ysis 
after a s h ort i nter val) d uri n g t he R u n-i n Peri o d t o e na ble e v al uati o n of t he s- P ra n d o mizati o n 
criteria. T o b e r a n d o mize d at Da y 1 ( Visit 4), s u bj ects m ust ha ve a s- P le v el ≥5. 5 a n d 
≤1 0. 0 m g/ d L  at Visit 3.  
S u bjects w h o d o n ot meet t he ra n d o mizati o n criteria base d o n t he s-P le vel  at Visit 3 will be 
disc o nti n ue d as scree n fail ures. S u bjects m ust c o nti n ue t o meet all ot her eli gi ble 
i ncl usi o n/e x cl usi o n criteria at ra n d o mizati o n. S u bjects w h o meet t he s -P criteria at Scree ni n g 
( Visit 1), b ut scree n fail d ue t o t he s- P le vel at Visit 3 ca n be re -scree ne d; t he y m ust w ait a 
mi ni m u m of o ne wee k after scree n f aili n g t o be re- scree ne d. 
D uri n g t h e D o u ble- Bli n d  Treat me nt Peri o d, s u bject s will recei ve te na pa n or or place b o 
starti n g at a d ose of 3 0 m g bi d (t hr ee 1 0 m g ta blets eac h ti me). T e na pa n or or place b o will be 
ta ke n t wice d ail y; j ust pri or t o brea kfast a n d di n ner. S u bject s s h o ul d n ot ta ke st u d y 
me dicati o n  at t he meal i m me diatel y prece di n g di al ysis.  
I n v esti gat ors ma y decrease or i ncrease t he d os e of st u d y me dicati o n  bas e d o n s-P le vels 
a n d/ or GI t oler a bilit y i n 1 0 m g i ncr e me nts t o a mi ni m u m of 1 0 m g bi d or a ma xi m u m of 
3 0 m g bi d after Ra n d o mizati o n ( Visit 4) t o Da y 1 5 ( Visit 6) . D oses ca n b e a dj uste d bet wee n 
visits.  
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 x a 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 gr a m  (E C G ), a n d A E  rec or din g.  
Bl o o d sa m ples will be c ollecte d , pr ocesse d t o ser u m or plas ma, a n d st ore d, as a p pr o priat e, f or 
t he p ote ntial e val uati o n of e x pl orat or y bi o mar kers.  


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 2 0  
4. 1. 1  
D ur ati o n of St u d y  
T he treat me nt d ur ati o n of t his st u d y will be  4 wee ks.  
5  
S E L E C TI O N A N D WI T H D R A W A L O F S U B J E C T S  
5. 1  
I ncl usi o n Criteri a 
A s u bject will be eli gi ble f or st u d y p artici pati o n if he/s he meets t he f oll o wi n g criteria:  
1.  
Si g ne d a n d d ate d i nf or m e d c o nse nt pri or t o a n y st u d y s pecific pr o ce d ures. 
2.  
Males or fe m ales 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, n o n-lactati n g a n d f ulfilli n g o ne of t he f oll o wi n g: 
a. P ost- me n o pa usal defi ne d as a me n orr h ea f or at least 1 2 m o nt hs f oll o wi n g cessati o n 
of all e x o ge n o us h or m o n al treat me nts a n d wit h f ollicle sti m ulati n g h or m o ne ( F S H) 
le vels i n t he la b orat or y d efi ne d p ost- me n o pa us al ra n ge. 
b.  D oc u me ntati o n of irr e versi ble s ur gical sterilizati o n b y h ysterect o m y, bilateral 
o o p h orect o m y or bilater al sal pi n gect o m y, b ut n ot t u bal li gati o n. 
c. Use of acce pt a ble c o ntr ace pti ve met h o d: i ntra uteri ne de vice ( I U D) wit h s per mici de, 
a fe male c o n d o m wit h s per mici de, c o ntrace pti ve s p o n ge wit h s per mici de, a n 
i ntra va gi nal s yst e m (e. g., N u va Ri n g® ), a di a p hra g m wit h s per mici de, a cer vical ca p 
wit h s per mici de, or or al, i m pla nta ble, tra ns der mal, or i njecta ble c o ntrace pti ves, 
se x ual a bsti ne nce, or a st erile se x ual part ner fr o m Scree ni n g u ntil 3 0 da ys after t he 
last s u bject visit . 
4.  
Males m ust a gree t o a v oi d fat heri n g a c hil d ( or d o nati n g s per m), a n d t heref ore be eit her 
sterile ( d oc u me nte d) or a gr ee t o use, fr o m t he ti me of enr oll me nt u ntil 3 0 da ys after e n d 
of st u d y, o ne of t he f oll o wi n g a p pr o ve d met h o ds of c o ntrace pti o n: a male c o n d o m wit h 
s per mici de, a sterile se x ual part ner, us e of a n I U D wit h s per mici de b y fe mal e se x ual 
part ner, a fe mal e c o n d o m wit h s per mici de, c o ntrace pti ve s p o n ge wit h s per mici de, a n 
i ntra va gi nal s yst e m (e. g., N u va Ri n g® ), a di a p hra g m wit h s per mici de, a cer vical ca p 
wit h s per mici de, or or al, i m pla nta ble, tra ns der mal, or i njecta ble c o ntrace pti ves. 
5.  
C hr o nic mai nte na nce he m o dial ysis ( H D) 3 x/ wee k f or at least 3  m o nt hs or c hr o nic 
mai nte na nce p erit 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, s u bject  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. 
6.  
If recei vin g acti ve vita mi n D or calci mi metics, t he d ose s h o ul d ha ve bee n u nc ha n ge d 
f or t he last 4 wee ks pri or t o Scree ni n g ( Visit 1). 
7.  
Kt/ V ≥1. 2 at m ost rece nt meas ure me nt pri or t o Scree ni n g ( Visit 1). 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 2 1  
8.  
P rescri be d a n d ta ki n g p h os p h ate bi n der me dicati o n at least 3 ti mes per da y . 
T he  prescri be d d ose s h o ul d ha ve bee n u n c ha n ge d d uri n g t he last 4 w ee ks pri or t o 
Scree ni n g ( Visit 1) . 
9.  
Ser u m p h os p h or us le vels m ust be ≥5. 5 a n d ≤1 0. 0 m g/ d L at Scree ni n g ( Visit 1) a n d t he 
e n d of t he R u n-i n Peri o d ( Visit 3) , a nal yze d at t he ce ntral la b orat or y use d i n t he st u d y.  
1 0.  
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 s u bject will n ot be eli gi ble f or st u d y p artici pati o n if he/s he meets a n y of t he f oll o wi n g 
e x cl usi o n criteria, or will be disc o nti n ue d at t he discreti o n of t he I n v esti 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 n e d as h a vi n g a n s- P le vel > 1 0. 0 m g/ d L o n p h os p hate-
bi n ders 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 parat h yr oi d h or m o ne > 1 2 0 0 p g/ m L. T he m ost rece nt v al ue fr o m t he 
s u bject’s me dical r ec 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 v esti gat or. 
4.  
Hist or y of i nfl a m mat or y b o wel disease (I B D) or irrita ble b o wel s y n dr o me wit h diarr hea 
(I B S-D).  
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 pl a ns t o rel ocat e t o a n ot her ce nter 
d uri n g t he st u d y peri o d. 
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 m e 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 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 h e s u bject is u na ble or u n willi n g t o f ulfill t he 
re q uire me nts of t h e pr ot o c 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  
S u bject Wit h dr a w al  
S u bjects 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 v esti gat or ma y re m o ve a s u bject 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 s u bject or t o t h e i nte grit y of t he 
st u d y data. If p ossi ble, all pr oced ur es f or earl y ter mi nati o n will  be c o m plete d ( Secti o n 8. 7 ).  


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 2 2  
5. 4  
E arl y Ter mi n ati o n of St u d y 
T he st u d y ma y b e ter mi n ate d at a n y ti me b y t he S p o ns or if seri o us si de effects 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 n efits 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 o ut if t he I n v esti gat or d oes n ot a d here t o t he 
pr ot oc ol or G C P . I n t h e e ve nt t hat t he cli nical de v el 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 v erseei n g t he trial.  
6  
T R E A T M E N T O F S U B J E C 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 n a pa n or h y dr oc hl ori d e is a n a m or p h o us, off- w hite t o w hite p o w der. Te n a pa n or ta blets will 
be s u p plie d as yell o w, o v al, bic o n ve x ta blets pac k a ge d i n H D P E b ottles wit h a desicca nt 
ca nister. Eac h b ottle c o nt ai ns si xt y ( 6 0) 1 0 m g ta blets a n d a desicca nt ca nister. A matc hi n g 
place b o will be i de nticall y s u p plie d i n H D P E b ottles.  
6. 1. 2  
Tre at me nts A d mi nistere d  
All s u bjects will re mai n o n t heir p h os p hate bi n der f or t he d urati o n of t h e st u d y. T he re s h o ul d 
be n o c ha n ge t o t he ir p h os p hate bi n der d ose f or t h e d urati o n of t he st u d y.  
Ta blets c o ntai ni n g 1 0 m g of te na pa n or or c orres p o n di n g place b o will be ta k e n orall y t wice 
dail y j ust pri or t o brea kfast a n d di n ner. O n dial ysis da ys, s u bjects o n H D s h o ul d n ot ta ke 
st u d y me dicati o n  at t he meal i m me diatel y pri or t o dial ysis a n d i nstea d ta k e it j ust pri or t o 
a n ot her meal . E ac h d ose of o ne t o t hree t a blets will ac hie ve t otal dail y d oses of 2 0, 4 0, or 
6 0 m g te na p a n or . 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 h er 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 v e bee n c o ns u me d. 
6. 1. 3  
D ose A dj ust me nts  
All s u bjects will st art at a d ose of 3 0 m g bi d (t hree 1 0 m g te na p a n or or pl ace b o ta bl ets eac h 
ti me). After r a n d o mizati o n ( Visit 4) t o Da y 1 5 ( Visit 6), d oses ca n be a dj uste d i n 1 0 m g 
i ncre me nts base d o n s- P le vels a n d/ or GI t olera bilit y. D o w n -titrati o n ca n g o fr o m 3 0 m g bi d 
t o 2 0 m g bi d a n d 2 0 m g bi d t o 1 0 m g bi d. D ose escalati o n ca n g o fr o m 1 0 m g bi d t o 2 0 m g 
bi d, a n d 2 0 m g bi d t o 3 0 m g bi d. D oses ca n be a dj uste d bet wee n visits. 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 2 3  
6. 1. 4  
Met h o d of Assi g ni n g S u bjects t o Tre at me nt  Gr o u ps  
After gi vi n g i nf or me d c o nse nt, s u bjects will be all ocate d se q u e ntial e nr oll me nt n u m bers at 
Scree ni n g ( Visit 1). 
A stratifie d ra n d o mizati o n sc he me will be e m pl o ye d t o t his st u d y, wit h t y p e of p h os p hate 
bi n der (s e vel a mer or n o n-se vela mer) a n d s-P le vel at Visit 3 ( < 7. 5 m g/ d L or ≥7. 5 m g/ d L) as 
t w o stratificati 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 pare t h e 
ra n d o mizati o n sc he me i n acc or d a nce wit h t he C R O’s sta n dar d o p erati n g pr oce d ures ( S O Ps) 
a n d t he ra n d o mizati o n pla n, w hic h reflect G o o d Cli nical Practice ( G C P) sta n dar ds. U p o n 
c o m pleti o n of t he R u n-i n Peri o d, eli gi ble s u bjects will be ra n d o mize d i n a 1: 1 rati o at Visit 4 
( Da y 1) t o r ecei v e te na p a n or or place b o.  
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 treat me nt 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 pri ate b ottle I D c h os e n fr o m t h ose b ottle I Ds a vaila bl e at t he st u d y site 
f or te na p a n or a n d place b o. As t he ra n d o mizati o n will n ot be stratifie d b y st u d y site,  t he 
assi g ne d ra n d o mizati o n n u m bers a n d t he ass o ciate d b ottle I Ds will n ot be s e q ue ntial wit hi n a 
st u d y site.  
If a s u bject wit h dr a ws fr o m t he st u d y, his/ her e nr oll me nt a n d ra n d o mizati o n n u m bers ca n n ot 
be re use d . 
6. 2  
I nvesti 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 m e dicati o n s are st ore d a n d dis pe nse d i n 
acc or d a nce wit h 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 n cer ni 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 p a n or a n d place b o 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. 
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 s ec 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 v esti gat or. T he I n vesti gat or or t h e I n vesti gat or’s 
desi g nee m ust mai ntai n acc urat e rec or ds of t he recei pt of all st u d y me dicati o n s 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 t he date recei ve d, 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 me dicati o n s. C urre nt 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 2 4  
dis pe nsi n g r ec or ds will als o be mai ntai ne d i ncl u di n g t he d ate a n d a m o u nt of st u d y 
me dicati o n s dis pe nse d a n d t he s u bject recei vi n g st u d y me dicati o n s. All re m a i ni n g st u d y 
me dicati o n s n ot re q uire d b y r e g ulati o ns t o be hel d b y t he cli nical facilit y m ust be ret ur ne d t o 
t he S p o ns or or t heir re prese ntati ve i m me diatel y aft er t he st u d y c o m pleti o n . 
6. 3  
P a c k a gi n g a n d L a beli n g  
6. 3. 1  
St u d y Me dic ati o n  
Te na pa n or ta blets ( 1 0 m g) are p a c k a ge d i n a n o p a q ue w hite H D P E b ottle ( 6 0 ta blets/ b ottle) 
wit h a w hite p ol y pr o p yl e ne c hil d resista nt cl os ure a n d i n d ucti o n seal pl us a desicca nt 
ca nister.  
A matc hi n g pl ace b o will be i de nticall y s u p plie d i n H D P E b ottles.  
St u d y m e dicati o n s 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. 
6. 3. 2  
Bli n di n g Met h o ds  
Place b o ta blets ar e i de ntical i n a p peara n ce (s h a pe, c ol or, size, etc.).  
O nl y t he p art y res p o nsi bl e f or la b eli n g, w are h o usi n g a n d s hi p pi n g dr u g s u p pl y; t he C R O or 
desi g nat e d i n de pe n d e nt s tatisticia n res p o nsi ble f or pre pari n g t he ra n d o mizati o n list; a n d t he 
I R T ma n a ger res p o nsi ble f or e ns uri n g me dicati o n  is a vaila ble at sites will ha ve k n o wle d ge of 
t he treat me nts assi g ne d d uri n g t he D o u ble- Bli n d  Treat me nt Peri o d . 
6. 4  
Pr oce d ure f or Bre a ki n g R a n d o miz ati o n C o de 
D uri n g t h e D o u ble- Bli n d  Treat me nt Peri o d , t he bli n d is t o be br o ke n o nl y w he n t he safet y of 
t he s u bject is at ris k a n d k n o wle d ge of t he st u d y me dicati o n  is esse ntial t o t he cli nical 
ma na ge me nt of t he s u bj ect. A decisi o n t o u n bli n d a s u bject m ust be ma de i n c o ncert wit h t he 
Me dical M o nit or a n d t he S p o ns or, e x ce pt i n e mer ge nc y sit uati o ns w he n t he bli n d m ust be 
br o ke n t o deter mi ne t h e treat me nt f or t h e s u bject. If a s u bject is u n bli n de d, t he date a n d 
reas o n f or t he u n bli n di n g m ust be rec or d e d o n s o urce d oc u m e nts. Please refer t o Secti o n 7. 4  
f or re p orti n g r e q uire m e nts. 
6. 5  
C o nc o mit a nt T her a p y  
T he use of c o nc o mita nt me dicati o ns d uri n g t h e D o u ble- Bli n d  Treat me nt Peri o d , u nless 
nee de d t o treat a n A E, s h o ul d be t he sa me as t he me dicati o ns use d a n d rec or de d at Scree ni n g 
( Visit 1) a n d d uri n g t he R u n- I n Peri o d .  


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 2 5  
All pri or a n d c o nc o mita nt me dicati o n s ( prescri pti o n a n d o ver-t h e-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 s u bj ect i n t he past 3 0 da ys will be rec or d e d i n 
t he Pri or & C o nc o mita nt Me dicati o n  electr o nic case re p ort f or m ( e C R F ) a n d will i ncl u de 
start a n d st o p date, d ose a n d r o ute of a d mi nistrati o n, fre q ue n c y, a n d i n dicati o n. Me dicati o ns 
ta ke n f or a pr oce d ure s h o ul d als o be i ncl u de d. 
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 d e d i n t he 
electr o nic d ata ca pt ure ( E D C) s yste m i n t he c orres p o n di n g e C R Fs. T h e I n vesti gat or will 
e ns ure acc ur ac y, c o m plete ness, a n d ti m eli ness of t he data rec or d e d a n d of t he pr o visi o n of 
a ns wers t o dat a q ueries . A n y c o m plete d e C R F m ust be si g ne d b y t he I n vesti gat or. A c o p y of 
t he c o m plete d e C R F will be arc hi v e d.  
7. 2  
D at a C ollecti o n Pri o r t o E nr oll me nt  
At Scree ni n g ( Visit 1), t h e f oll o wi n g i nf or mati o n will be c ollecte d fr o m e v er y partici p a nt t o 
i de ntif y eli gi ble s u bjects f or f urt her assess me nts: 
•  Assess me nt of t he diseas e stat us o utli ne d i n t he i ncl usi o n/e x cl usi o n criteria  
•  Date of birt h, ge n d er, a n d race  
•  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 pres cri be d dail y d ose ( m ust be t hree ti mes a da y) 
•  P h ysical e x a mi nati o n  
•  Vital si g ns ( pr e -dial ysis)  
•  Electr ocar di o gra m e v al u ati o n  
•  Bl o o d sa m ple f or cli nical la b orat or y c h e mistr y a n d he mat ol o g y tests ( pre -dial ysis)  
•  F S H a n d pr e g na nc y t est, if a p plica ble 
•  C o nc o mita nt me dicati o ns  
7. 3  
S af et y V ari a bles 
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 x a mi nati o ns,  b o d y w ei g ht, vital si g ns, safet y la b orat or y tests, 1 2- lea d E C G , a n d A E  
rec or di n g. B o d y w ei 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  b e 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 2 6  
perf o rme d pre -di al ysis . All ot her assess me nts ma y be p erf o r me d pre-, d uri n g, or p ost-di al y sis 
b ut s h o ul d be perf or me d at t he sa me ti me at eac h visit.  
7. 3. 1  
P h ysic al E x a mi n ati o n 
T he p h ysi cal e x a mi nati o n will i ncl u de a n assess m e nt of t he f oll o wi n g ite ms: ge neral 
a p pear a nce, s ki n (i ncl u di n g a n y pitti n g e de m a 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 r elati ve t o eac h s u bject’s p h ysical e x a mi nati o n will be caref ull y 
d oc u me nte d i n t he e C R F. 
7. 3. 2  
Vit al Si g ns ( bl o o d press ure a n d he art r ate)  
Bl o o d press u r e a n d h eart rate will be o btai ne d at all visits ( pre-dial ysis) . S yst olic a n d 
diast olic bl o o d press ure will be meas ure d after t h e s u bject  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 me nts will be rec or d e d o n t he s o urce d oc u m e n t 
a n d i n t he e C R F. 
7. 3. 3  
Electr oc a r di o gr a m  
A 1 2 -lea d E C G will be p erf or me d after t he s u bject has bee n i n a sitti n g or s u pi ne p ositi o n f or 
at least 5 mi n utes . 
T he f oll o wi n g E C G p ara meters will be rec or de d: heart rate, P R -i nter val, Q R S- d urati o n, 
Q T -i nter val ( u n c orr ecte d), Q Tc-i nter val (c orrecte d), R R-i nter val a n d t he I n vesti gat or’s 
c o ncl usi o n o n t he E C G pr ofile.  
T he I n vesti gat or will ass ess w het her t h e E C G is n or mal or a b n or mal; a b n or mal will be 
f urt her s u b di vi de d i nt o cli nicall y si g nifica nt a n d n ot cli nicall y si gnifica nt . 
Electr ocar di o gra p hic i nter vals a n d t he I n v esti 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.  
7. 3. 4  
Cli nic al L a b or at or y Tests 
Sa m ples m ust  be o bt ai ne d, pre- dial ysis, f or t he h e mat ol o g y a n d c he mistr y cli nical la b orat or y 
tests i de ntifie d i n Ta ble 7- 1 .  
Ot her e val u ati 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 Ass es s me nts a n d Pr oce d ures (Secti o n 1. 3 ), will i ncl u de:  


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 2 7  
•  F S H test , if a p plica ble 
•  Pre g n a nc y test, if a p plica ble 
7. 3. 5  
A n al ysis of Cli nic al L a b or at or y Tests 
A certifie d l a b orat or y will be use d t o pr ocess a n d pr o vi de res ults f or t he cli nical la b orat or y 
tests. T he baseli ne la b or at or y test r es ults f or cli nical assess me nt f or a partic ular test will be 
defi ne d as t he l ast meas ure me nt pri or t o t he i nitial d ose of st u d y m e dicati o n . 
F or a n y l a b orat or y test v al ue o utsi de t he refere nce ra n ge t h at t he I n ve sti gat or c o nsi ders 
cli nicall y si g nifica nt, t he I n v esti gat or will:  
•  Re peat t he test t o verif y t he o ut - of-ra n ge v al 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 h e I n v esti gat or c o nsi ders 
cli nicall y si g nifica nt, or ( 2) t hat re q uires a s u bject 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 s u bj ect t o recei v e n o n- st u d y treat me nt, or ( 4) f ulfills o ne or m ore criteri a f or 
seri o us a d vers e e v e 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 
C he mistr y b  
Ot her 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 ( %)  
B as 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 o tassi u m 
S o di u m  
F S H  
Ser u m 
pre g na nc y  
 
a W h ole bl o o d.  
b Ser u m.  
c Ser u m p h os p h or us is als o 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 test c o nfir ms p ost -me n o pa usal stat us . 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 2 8  
7. 4  
A d verse E ve nts  
T he I n vesti gat or is r es p o nsi ble f or e ns uri n g t hat all staff i n v ol ve d i n t he st u d y are fa miliar 
wit h t he c o nte nt of t his secti o n. 
A n A E  is defi ne d as a n y u nt o war d me dical o cc urre nce i n a s u bject a d mi nistere d a 
p har mace utical pr o d uct d uri 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 or a ble a n d u ni nte n de d si g n, s y m pt o m, or disease te m p orall y ass o ciate d wit h t he use 
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. 
S u bject s 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 ni n 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 s u bject 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 h e st u d y p ers o n nel 
s uc h as “ H a 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 r ec or d e 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 di a 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 n ces of w ell-rec o g nize d s y m pt o ms, t he y ca n be rec or d e d as t he c o m m o nl y us e d 
dia g n osis ( e. g., fe v er, r u n n y n ose, a n d c o u g h ca n b e 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 p art 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 p aratel y. 
A d verse e ve nts t hat ar e i de ntifie d as s pecifie d i n t he pr ot oc ol m ust be rec or de d o n t he A E 
e C R F wit h t he stat us of t he A E n ote d. 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 ha uste 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 h e pr oce d ures 
s pecifie d i n Secti o n  7. 4. 8  are t o be f oll o we d f or re p orti n g S A Es. 
7. 4. 1  
A d verse E ve nts Ass oci ate d wit h C h a n ge i n St o ol F or m a n d/ or Fre q ue nc y  
Base d o n t e na pa n or’s a bilit y t o i n hi bit t he a bs or pti o n of dietar y s o di u m, it is k n o w n t o alter 
st o ol f or m a n d fre q u e nc y i n s o me s u bjects. F or a c ha n ge i n st o ol f or m a n d/ or fre q u e nc y t o be 
c o nsi dere d a n A E , t he s u bject m ust c o nsi der t he b o wel m o ve me nts t o be “ b ot hers o me”.  
7. 4. 2  
Rec or di n g A d verse E ve nts  
A d verse e ve nts ar e t o be rec or d e 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: 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 2 9  
•  Mil d : T he s u bject 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 pecifi c treat me nt . 
•  M o derate: T he s u bj ect  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 h e c o n diti o n re q uires s pecifi c trea t me nt. 
•  Se vere:  T he s u bject is i nca pacitate d wit h i na bilit 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 uir es si g nifi ca nt treat me nt meas ures.  
Acti o n ta ke n will be cate g orize d as d os e n ot c ha n ge d, d os e re d u ce d, dr u g i nterr u pte d, dr u g 
wit h dra w n, re q uire d c o n c o mita nt me dicati o n, re q uire d c o nc o mita nt pr o ce d ure, a n d/ or ot her. 
E ve nt o utc o me at r es 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 v ere d/res ol ve d wit h se q uelae, rec o v eri n g/res ol vi n g, fatal, 
or u n k n o w n. 
7. 4. 3  
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 me dicati o n  (te na pa n or or place b o) s h o ul d be 
deter mi ne d b y t he I n v esti 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 uce d b y ot her fact or s s uc h as t he s u bject’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 n s, a n d d oes n ot f oll o w a 
k n o w n res p o nse p atter n t o t he st u d y me dicati o n , or t he te m p oral relati o ns hi p of t he e ve nt 
t o st u d y me dicati o n  a d mi nistrati o n ma kes a ca us al relati o ns hi p u nli kel y. 
•  P ossi bl y r elate d: T he e ve nt f oll o ws a reas o n a ble te m p oral se q ue nce fr o m t h e ti me of 
me dicati o n  a d mi nistrati o n, a n d is p ossi bl y d ue t o me dicati o n  a d mi nistrati o n a n d ca n n ot 
be reas o n a bl y e x plai ne d b y ot her fact ors s uc h as t he s u bject ’s cli nical c o n diti o n, 
i nterc urr e 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 fr o m t he ti me of me dicati o n  
a d mi nistrati o n, a n d/ or f oll o ws a k n o w n res p o nse p atter n t o t he st u d y m e dicati o n , a n d 
ca n n ot be r eas o na bl y e x plai ne d b y ot h er fact ors s u c h as t he s u bject ’s cli nical c o n diti o n, 
i nterc urr e nt ill ness, or c o nc o mita nt me dicati o ns. 
7. 4. 4  
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, 
or u ntil a ll 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. T he I n v esti gat or 
s h o ul d use his/ her discreti o n i n or deri n g a d diti o nal tests as necess ar y t o m o nit or t he 
res ol uti o n of s uc h A Es . 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 3 0  
7. 4. 5  
Disc o nti n u ati o n d ue t o A d verse E ve nts  
A n y s u bject w h o e x perie nces a n A E m a 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 v esti gat or. S u bject s wit h dra w n fr o m t he st u d y d u e t o a n A E, w het her 
seri o us or n o n-seri o us, m ust be f oll o we d b y t he I n vesti gat or u ntil t he cli nical o utc o me of t he 
A E is deter mi n e d; refer t o Secti o n 8. 7 . T he A E(s) s h o ul d be n ote d o n t he a p pr o priate C R Fs 
a n d t he s u bject’s pr o gress s h o ul d be f oll o we d u ntil t he A E is res ol ve d or st a bilize d . A 
decisi o n t o disc o nti n ue a s u bject 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 me dicati o n , t he I B s h o ul d be c o ns ulte d f or details 
re gar di n g a n y s pecifi c acti o ns t o be ta ke n. 
7. 4. 6  
Pre g n a nc y  
Fe male s u bjects m ust be i nstr ucte d t o disc o nti n ue all st u d y me d icati o ns a n d i nf or m t he st u d y 
I n v esti gat or i m me diatel y if t he y b ec o me pre g na nt d uri n g t he st u d y. 
T he I n vesti gat or m ust re p ort a n y pre g n a nc y t o M e d pace Cli nical Safet y wit hi n 1 b usi ness 
da y of bec o mi n g a war e of it . T he s u bject  m ust be i m me diatel y disc o nti n u e d fr o m f urt her 
treat me nt wit h st u d y me dicati o n. 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 nci es will be f oll o we d t hr o u g h birt h. 
Pre g n a ncies are ca pt ur e d if t he y o cc ur i n fe male s u bject s or i n t he se x ual part ners of m ale 
s u bjects fr o m t he ti me t he s u bject is first e x p ose d t o t he i n vesti gati o nal pr o d uct u ntil 3 0 da ys 
after last e x p os ure t o t he i n vesti gati o nal pr o d u ct. 
A n y c o n ge nital a b n or m alities i n t he offs pri n g of a s u bject w h o recei ve d st u d y me dicati o n  
will be re p orte d as a n S A E. T he o utc o me of a n y pre g n a nc y a n d t he pres e nce or a bse n ce of 
a n y c o n ge nital a b n or malit y will be rec or d e d i n t he s o urce d oc u m e ntati o n a n d re p orte d t o 
Me d pace Cli nical Saf et y.  
7. 4. 7  
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 hr 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 vers e dr u g e x perie nce 
•  I n p atie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n 
•  A persiste nt or si g nifica nt disa bilit y/i nca p acit y  
•  A c o n ge nital a n o mal y/ birt h defect  


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 3 1  
I m p ort a nt me dical e v e 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 dere d a n S A E w h e n, base d u p o n a p pr o priate me dical j u d g m e nt, 
t he y ma y j e o par dize t he s u bject a n d ma y re q uire m e 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 x a m ples of s uc h me dical e ve nts i ncl u de 
aller gic br o n c h os pas m re q uiri n g i nte nsi ve treat me nt i n a n e mer ge n c 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 d e pe n de nc y or dr u g a b use. 
N ote:  S A Es re q uire i m m e diate re p orti n g t o Me d p ace Cli nical Safet y . See “ Re p orti n g Seri o us 
A d verse E v e nts” bel o w f or details.  
7. 4. 8  
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 r e p orte d or o bs er 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 me dic ati o n , site pers o n nel will re p ort it t o 
 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 S A E e C R F i n t he E D C s yste m f or t h e st u d y. W he n t he f or m 
is c o m plete d, 
 will be n otifie d electr o ni call y a n d will 
retrie ve t h e f or m. If t he e ve nt meets seri o us criteri a a n d it is n ot p ossi ble t o access t he E D C 
s yste m, se n d a n e mail t o 
 ( p h o n e n u m ber liste d 
bel o w), a n d f a x/e mail t he c o m plete d pa per bac k - u p S A E f or m t o  
(c o ntact 
i nf or mati o n liste d bel o w) wit hi n 2 4 h o urs of a ware ness. W he n t he E D C s yste m bec o mes 
a vaila ble, t he S A E i nf or mati o n m ust be e ntere d wit hi n 2 4 h o urs of t he s yste m bec o mi n g 
a vaila ble. I n c o mi n g re p orts are r e vie w e d d uri n g n or mal b usi ness h o urs.  
Safet y C o ntact I nf or m ati o n: 
 
 
 
  
T he I n vesti gat or is r e q uir e d t o s u b mit S A E re p orts t o t he I R B/I n de p e n de nt Et hics C o m mittee 
(I E C) i n acc or da n ce wit h l ocal re q uire me nts. All I n vesti gat ors i n v ol ve d i n trials usi n g t he 
sa me i n vesti gati o nal pr o d uct will recei ve s afet y alert n otificati o ns f or o n w ar d 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 v esti gat ors will be bli n de d. 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 3 2  
F oll o w- U p Re p orts 
T he I n vesti gat or m ust c o nti n ue t o f oll o w t he s u bject u ntil t he S A E has res ol ve d or u ntil t he 
c o n diti o n bec o mes c hr o nic i n nat ure, sta bilizes (i n t he case of persiste nt i m pair me nt) , or t he 
s u bject dies.  
Wit hi n 2 4 h o urs of recei pt of f oll o w- u p i nf or mati o n, t he I n vesti gat or m ust u p date t he 
S A E  e C R F i n t he E D C s yste m f or t he st u d y a n d s u b mit a n y s u p p orti n g d o c u me ntati o n 
(e. g., s u bject disc har ge s u m mar y or a ut o ps y re p orts) t o 
 
via fa x or e -mail . If it is n ot p ossi ble t o access t he E D C s yste m, refer t o t he pr oce d ures 
o utli ne d a b o ve f or i nitial re p orti n g of S A Es.  
7. 5  
Effic ac y E n d p oi nts  
Ser u m p h os p h or us le vels will be meas ure d at all st u d y visits . T he pri mar y efficac y e n d p oi nt 
is t he c ha n ge fr o m baseli ne i n s-P le vel at Wee k 4. T he effi cac y of te na p a n or as a n a dj u n cti ve 
t hera p y t o p h os p hate bi n der t her a p y will be e val u ate d base d o n t he differe nce i n mea n c ha n ge 
fr o m baseli ne i n s-P le vel at Wee k 4 bet wee n t he t e na pa n or a n d place b o gr o u ps. 
T he f oll o wi n g effi cac y e n d p oi nts will be a nal yz e d as ke y sec o n d ar y e n d p oi nts: 
•  s-P r es p o nse (ac hie vi n g a n s- P le vel < 5. 5 m g / d L) at Wee k 4 
•  Relati ve  cha n ge fr o m bas eli ne  i n i F G F 2 3 at Wee k 4, deri ve d as  
(i F G F 2 3 at Wee k 4/ baseli ne i F G F 2 3 – 1)  
•  Relati ve  cha n ge fr o m bas eli ne  i n cF G F 2 3 at Wee k 4 , deri ve d as  
(c F G F 2 3 at Wee k  4/ baseli ne c F G F 2 3 – 1) 
Ot her sec o n d ar y e n d p oi nts t o be a nal yze d i ncl u d e:  
•  C ha n ge fr o m bas eli ne i n s- P le vel at Wee k 1, Wee k 2, a n d Wee k 3 
•  s- P res p o nse at Wee k 1, Wee k 2, a n d Wee k 3 
•  C ha n ge fr o m bas eli ne i n P T H at Wee k 4  
8  
M E T H O D O L O G Y/ S T U D Y VI SI T S  
8. 1  
Scree ni n g Pr oce d ures : Visit 1 ( D a ys - 3 0 t o - 1 4) 
T he I n vesti gat or will i nf or m eac h pr os pecti ve s u bject 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 ns e nt fr o m t he s u bject pri or t o per f or mi n g a n y 
st u d y-r elate d pr o ce d ur es. 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 3 3  
Scree ni n g e v al uati o ns will c o nsist of t he f oll o wi n g:  
•  Assess me nt of t he diseas e stat us o utli ne d i n t he i ncl usi o n/e x cl usi o n criteria  
•  Kt/ V – t he m ost rece nt v al ue pri or t o Scree ni n g  
•  Date of birt h, ge n d er, a n d race  
•  Wei g ht ( pre- dial ysis) a n d hei g ht  
•  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 pres cri be d dail y d ose ( m ust be t hree ti mes a da y) 
•  P h ysical e x a mi nati o n  
•  Vital si g ns ( pr e -dial ysis)  
•  Electr ocar di o gra m  e v al u ati o n  
•  Bl o o d sa m ple f or cli nical la b orat or y c h e mistr y a n d he mat ol o g y tests ( pre -dial ysis)  
•  F S H a n d pr e g na nc y t est, if a p plica ble 
•  C o nc o mita nt me dicati o ns  
S u bjects will be i nstr ucte d n ot t o ta ke a n y ot her m e dicati o ns wit h o ut t he a p pr o val of t he 
I n v esti gat or (e x ce pt t heir e xisti n g p h os p hate bi n der me dicati o n ). Res ults of t he scree ni n g 
e val uati o ns m ust meet t he i ncl usi o n/e x cl usi o n criteria f or t h e s u bject t o be e nr olle d i n t he 
st u d y. 
8. 2  
R u n -i n Pr oce d ures: Visit 2 ( D a ys - 1 8 t o -7) a n d Visit 3 ( D a ys - 9 t o - 2) 
•  Ser u m p h os p h or us meas ure me nt ( pre-dial ysis)  
•  C o nc o mi ta nt me dicati o n 
•  A E assess me nts  
8. 3  
Visit 4 ( D a y 1) 
•  I n cl usi o n/e x cl usi o n criteria (assess s-P criteria usi n g t he s- P meas ure me nt at  Visit 3  a n d 
c o nfir m ot her a p plica ble i ncl usi o n/e x cl usi o n criteria) 
•  Vital si g ns  ( pr e-dial ysis)  
•  Ser u m p h os p h or us meas ure me nt ( pre- dial ysis)  
•  Bl o o d c ollecti o n f or bi o mar ker sa m ple ( pre-dial ysis)  
•  Bl o o d c ollecti o n f or F G F 2 3 a n d P T H ( pre- dial ysis)  
•  Ra n d o mizati o n 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 3 4  
•  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)  
•  C o nc o mita nt me dicati o ns  
•  St u d y m e dicati o n  dis pe nsi n g 
•  A E assess me nt  
8. 4  
Visit s 5, 6, a n d 7 ( D a ys 8, 1 5, a n d 2 2 ± 2 D a ys) 
•  Ser u m p h os p h or us meas ure me nt ( pre-dial ysis)  
•  St u d y m e dicati o n  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  
•  A E assess me nt  
8. 5  
Visit 8 ( D a y 2 9 ± 2 D a ys) 
•  Wei g ht ( pre -dial ysis)  
•  Vital si g ns ( pr e-dial ysis)  
•  Bl o o d c ollecti o n f or bi o mar ker sa m ple ( pre- dial ysis)  
•  Bl o o d c ollecti o n f or F G F 2 3 a n d P T H ( pre- dial ysis)  
•  P h ysical e x a mi nati o n  
•  Electr ocar di o gra m  ev al u ati o n  
•  Bl o o d sa m ple f or cli nical la b orat or y c h e mistr y a n d he mat ol o g y tests ( pre -dial ysis)  
•  Bl o o d s a m ple f or s er u m p h os p h or us ( pre- di al ysis)  
•  Pre g n a nc y test  (f or w o m e n of c hil d-beari n g p ote ntial)  
•  St u d y m e dicati o n  ret ur n 
•  C o nc o mita nt me dicati o n  
•  A E assess me nt  
8. 6  
E arl y Ter mi n ati o n Visit  
E val uati o ns sc he d ule d f or Visit 8 will be perf or me d at t he Earl y Ter mi nati o n visit  f or 
s u bjects w h o pre mat ur el y disc o nti n ue fr o m 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 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 3 5  
8. 7  
Wit h dr a w al Pr oce d ures  
I n t he e ve nt of a s u bject’s wit h dra wal, e v er y eff ort will be ma de t o c o m plete t he 
E n d - of-St u d y assess me nts  ( Visit 8). Wit h dra w n s u bjects will be f oll o we d u ntil res ol uti o n of 
a n y A Es or u ntil t he u nres ol ve d A Es are j u d ge d b y t he I n v esti gat or t o ha ve sta bilize d. 
8. 8  
Criteri a f or St u d y Ter mi n ati o n  
T he st u d y ma y b e ter mi n ate d at a n y ti me b y t he S p o ns or if S A Es occ ur, or if, i n t he 
S p o ns or’s j u d g me nt, t her e are n o f urt her be nefits t o be ac hie v e 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 o ut if t he I n v esti gat or d oes n ot a d here t o t he 
pr ot oc ol. I n t he e v e nt t hat t he 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 wil l i nf or m all I n v esti gat ors/i nstit uti o ns a n d t he I R B o vers eei n g 
t he st u d y. 
8. 9  
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 s u bject 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 at e Bl o o d V ol u me per S u bject  
Test  
N o. of S a m ples  
V ol u me C ollecte d 
f or E ac h Sa m ple 
( m L) 
T ot al ( m L)  
C he mistr y + b -H C G + F S H  
2 
7 
1 4  
He mat ol o g y ( bl o o d)  
2 
3 
6 
P h os p h or us (ser u m)  
8 
4 
3 2  
P T H ( plas ma ) 
2 
4 
8 
iF G F -2 3 ( plas ma) 
2 
4 
8 
cF G F -2 3 ( plas ma) 
2 
4 
8 
Ser u m bi o mar kers  
2 
5 
1 0  
Plas ma bi o mar kers  
2 
6 
1 2  
T ot al  
-- 
-- 
9 8  


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 3 6  
8. 1 0  
Pr ot oc ol D e vi ati o ns 
S u bjects m ust f ull y meet t he f oll o wi n g criteria i n or der t o be e nr olle d i n t he st u d y. I n kee pi n g 
wit h re g ul at or y re q uire m e nts, if t he S p o ns or al l o ws a s u bject t o c o nti n ue i n t he st u d y 
f oll o wi n g a pr ot oc ol de vi ati o n, t he de viati o n m ust be rec or de d as s uc h. 
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 o c ol pr oce d ures or re q uir e me nts. D e viati o ns ma y 
res ult fr o m t he acti o n or i nacti o n of t he s u bject, t h e I n vesti gat or, or site staff. E x a m ples of 
de viati o ns i ncl u de, b ut ar e n ot li mite d t o:  
•  Fail ure t o a d h er e t o st u d y i ncl usi o n or e x cl usi o n criteria  
•  Fail ure t o c o m pl y wit h dis pe nsi n g or d osi n g re q uire me nts 
•  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 
pr o hi bite d i n t he pr ot oc ol 
•  Misse d or o ut- of- wi n d o w visits 
•  Dr u g d osi n g n ot a d mi nist ere d wit hi n t he ti me fra me s pecifie d i n t he pr ot oc ol  
•  Fail ure t o  a d h er e t o test r e q uire me nts, i ncl u di n g vital si g ns, la b orat or y tests, p h ysi cal 
e x a mi nati o n , me dical hist or y; eit her tests n ot d o ne, i nc orrect tests d o ne, or n ot d o ne 
wit hi n t he ti me fra me s pecifie d i n t he pr ot oc ol  
•  Pr oce d ural d e viati o ns s uc h as i nc orrect s t ora ge of st u d y me dicati o n , fail ure t o u p date t he 
i nf or me d c o nse nt f or m (I C F) w he n n e w ris ks bec o me k n o w n, or fail ure t o o btai n I R B 
a p pr o vals f or t h e pr ot oc ol a n d I C F re visi o ns 
At t he o utset of t he st u d y, a pr ocess f or defi ni n g a n d ha n dli n g pr ot oc ol d e viat i o ns will be 
esta blis he d . T his will i ncl u de deter mi ni n g w hic h vi olati o ns will be desi g n ate d “critical ”, 
re q uiri n g i m me diate n otificati 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 seei n g t hat all k n o w n pr ot oc ol de viati o ns a re rec or d e d a n d ha n dle d as a gree d. 
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 statistical a nal ysis pla n ( S A P) will be  pr o vi de d se paratel y. N o c h a n ges are e x pecte d 
t o t he pri mar y a n d sec o n dar y efficac y a nal ys es . If t he la n g u a ge i n t his pr ot oc ol a n d t he 
la n g u a ge i n t he S A P diff er, t he S A P g o v er ns. Res ults o btai ne d fr o m t he a n al yses s p ecifie d i n 
t he fi nal a p pr o v e 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 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 3 7  
t his st u d y. A n y d e viati o ns fr o m t he fi nal a p p r o v e 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 2 1 4 E S R D s u bjects wit h h y p er p h os p hate mia will be ra n d o mize d i n a 1 : 1 rati o 
t o recei ve eit her te n a pa n or or place b o.  
T he pri mar y e n d p oi nt is t he c ha n ge fr o m bas eli ne  i n s-P le vel at Wee k 4 . Ass u mi n g a 
c o m m o n sta n dar d de viati o n of 1. 0 m g/ d L, a s a m ple size of 2 1 4 s u bjects (1 0 7 s u bjects/ gr o u p) 
is e x pecte d t o pr o vi de 9 5 % p o wer t o det ect a treat me nt differe n ce of - 0. 5 m g/ d L i n t he 
pri mar y e n d p oi nt bet wee n t he te na pa n or a n d place b o gr o u ps. T his calc ulati o n is base d o n a 
t w o-sa m ple t-test wit h a si g nifica n ce le v el of 0.0 5 (t w o-si de d) usi n g S A S ®  P R O C P O W E R . 
U n der t he sa m e ass u m pti o ns state d a b o ve, t he sa m ple size of 2 1 4 s u bjects will pr o vi de at 
least 8 5 % p o wer at t he 0. 0 1 si g nifica n ce le v el.  
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 nte nt- t o-Treat (I T T) p o p ulati o n, F ull 
A nal ysis Set  ( F A S), Per- Pr ot oc ol ( P P) p o p ulati o n, Wee k 4 C o m pleters, a n d Safet y 
p o p ulati o n.  
•  I nte nt-t o-Trea t P o p ulati o n: will be c o m prise d of all ra n d o mize d s u bjects.  
•  F ull A nal ysis Set: will i ncl u de all I T T s u bjects w h o ha ve at least o ne p ost- b aseli 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 t o b e 
perf or me d wit h s u bjects as ra n d o mize d.  
•  Per - Pr ot oc ol P o p ulati o n: will be a s u bset of t he F A S. It will be t he a n al ysis p o p ulati o n f or 
se nsiti vit y a nal ysis t o be perf or me d wit h s u bjects as ra n d o mize d. A n y s u bject w h o has a 
si g nifica nt pr ot o c ol de viati o n t hat c o ul d alter his/ her efficac y o utc o me t o treat me nt will 
be e x cl u de d fr o m t he P P p o p ulati o n.  
•  Wee k 4 C o m pleters: will be a s u bset of t he F A S. It will i ncl u de all F A S s u bjects w h o 
c o m plete t he s-P assess m e nt at Wee k 4 . It will be t he a nal ysis p o p ulati o n f or se nsiti vit y 
a nal ysis t o be p erf or me d wit h s u bjects as ra n d o mi ze d.  
•  Safet y P o p ulati o n: will i ncl u de all I T T s u bjects w h o recei v e at least o ne d ose of t he st u d y 
me dicati o n  (te na p a n or or place b o). It will be t he a nal ysis p o p ulati o n f or safet y a nal yses t o 
be perf or me d wit h s u b jects as treate d.  


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 3 8  
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 treat me nt ( pla n ne d or act uall y recei v e d) . 
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 d ar d de viati o n, 
me dia n, mi n i 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 bl es. S u m mar y 
statistics f or i F G F 2 3 a n d c F G F 2 3 will als o i ncl u de ge o m etric mea n a n d ge o metric c oefficie nt 
of variati o n %. Fre q u e 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 s u bject data i n cl u di n g r ele va nt deri ve d varia bles will be liste d. 
A nal ys es of efficac y e n d p oi nts will be perf or me d  o n t he F A S a n d t he P P p o p ulati o n. 
T he  statistical testi n g will be c o n d ucte d at a si g nifica nce l e vel of 0. 0 5 (t w o-si de d) u nless 
s pecifie d ot her wise. A nal ys es of saf et y m eas ures will be perf or me d o n t h e Safet y p o p ulati o n . 
N o statistical testi n g will be c o n d ucte d f or safet y meas ures.  
All data ma ni p ulati o ns, descri pti ve s u m maries, a n d statistical h y p ot hesis testi n g will be 
perf or me d usi n g S A S ® . 
9. 4. 2  
B aseli ne Descri pti ve St atistics  
Baseli ne c har acteristics, i ncl u di n g de m o gra p hics, disease c h aracteristics, pri or/c o nc o mita nt 
me dicati o ns, a n d me dical/s ur gical hist or y will be s u m marize d b y pla n ne d treat me nt.  
9. 4. 3  
Pri m ar y Effic ac y A n al ysis 
T he pri mar y effi cac y e n d p oi nt is t he c ha n ge fr o m baseli ne i n s-P le vel at Wee k 4. F or t his 
c o nti n u o us e n d p oi nt, t he f oll o wi n g pair of h y p ot heses will be teste d:  
H 0: µt = µ p 
vers us 
H 1: µt ≠ µ p 
w here µ t a n d µp de n ote t he mea n c h a n ges fr o m baseli ne i n s - P le vel at Wee k 4 i n te na pa n or 
a n d place b o gr o u ps, res p ecti vel y. As  t he pri mar y a nal ysis, t he treat me nt c o m paris o n of t he 
mea n c ha n ge will be perf or me d usi n g a mi x e d -effects m o del f or re peate d meas ures  ( M M R M) 
o n o bser ve d cases of t h e F A S . T he M M R M  will i ncl u de t y p e of p h os p hat e bi n der (se vel a mer 
or n o n- se vela m er), s- P le vel at Visit 3 ( < 7. 5 m g/ d L or ≥7. 5 m g/ d L), treat m e nt, visit ( Wee k 1 
t hr o u g h Wee k 4), treat m e nt -b y -visit i nteracti o n as fi x e d effects; baseli ne ( Visit 4) s-P le vel  
a n d baseli ne- b y -visit as c o variates; a n d s u bject as a ra n d o m effect . A n u nstr uct ure d ( U N) 
c o varia n ce matri x will be use d t o m o del t he wit hi n -s u bject err ors. T he l east s q uares mea n of 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 3 9  
s-P c ha n ge s wit hi n eac h treat me nt g r o u p will be re p orte d . T he differe n ce i n mea n s -P 
c ha n ges at Wee k 4 b et wee n t he te na p a n or a n d place b o gr o u ps, al o n g wit h t he 9 5 % 
c o nfi de nce i nter val ( CI), 9 9 % CI, a n d p -val u e will als o be re p ort e d .  
T he  effi cac y of te na p a n or as a n a dj u n cti ve t hera p y t o p h os p hate bi n der t hera p y will be 
c o ncl u de d if t he esti mate d differe n ce b et wee n t h e te na pa n or a n d place b o gr o u ps i n t he mea n 
s-P c ha n ge fr o m baseli ne at Wee k 4 is ne gati ve (i. e., < 0) a n d t he c orres p o n di n g t w o-si de d 
p - val ue ≤0. 0 5. 
9. 4. 4  
Sec o n d ar y Effic ac y A n al yses 
F o r bi nar y res p o nse e n d p oi nts, t he s- P res p o nse rate (i.e., t he pr o p orti o n of s u bjects a c hie vi n g 
a n s-P le vel  < 5. 5 m g/ d L) at eac h p ost-b aseli ne visit will be esti mate d f or eac h treat me nt 
gr o u p a n d be c o m pare d b et wee n t he t e na pa n or a n d place b o gr o u ps wit h t he 9 5 % a n d 9 9 % 
CI s. T he p  v al ue will be o btai ne d fr o m t he C oc hra n -Ma ntel -H ae nszel test a dj usti n g f or  t y pe 
of p h os p hate bi n der (se v ela mer or n o n- se vel a mer) a n d s-P le vel at Visit 3 ( < 7. 5 m g/ d L or 
≥7. 5 m g/ d L) .  
T he  relati ve c ha n ge fr o m baseli ne i n i F G F 2 3 ( or c F G F 2 3) at Wee k 4 will b e a nal yz e d usi n g 
a n a nal ysis of varia nce ( A N O V A) m o d el wit h l o g-tra nsf or me d relati ve c h a n ge at Wee k 4 as 
t he de pe n de nt v aria ble. T he m o del will i ncl u de t y p e of p h os p hate bi n der (se vela mer or 
n o n- se vela mer), s-P le vel at Visit 3 ( < 7. 5 m g/ d L or ≥7. 5 m g/ d L) , a n d treat me nt as fact ors . 
Bac k -tra nsf or me d p oi nt esti mates a n d CIs ( 9 5 % a n d 9 9 %) will be re p orte d.  
Mea n c ha n ges fr o m b aseli ne i n s -P le vel at Wee k 1, Wee k 2, a n d Wee k 3 will be esti mate d 
f or eac h treat me nt gr o u p a n d be c o m pare d bet w ee n t he te na pa n or a n d place b o gr o u ps usi n g 
t he M M R M of t he pri mar y a nal ysis.  
T he c ha n ge fr o m bas eli ne i n P T H at Wee k 4 will be a nal yz e d usi n g a n a n al ysis of c o v aria nce 
( A N C O V A) mo d el wit h P T H c ha n ge at Wee k 4 as t he de pe n de nt varia ble. T he m o del will 
i ncl u de t y p e of p h os p hat e bi n der (se v ela mer or n o n -se vela mer), s-P le vel  at Visit 3 
( < 7. 5 m g/ d L or ≥7. 5 m g/ d L) , tr eat me nt as fact ors a n d baseli ne P T H le v el as a c o vari ate.  
9. 4. 5  
M ulti ple  C o m p aris o ns / M ulti plicit y 
T o c o ntr ol t he o ver all T y pe I err or r ate ass oci ate d wit h m ulti ple c o m paris o ns o n t he pri mar y 
a n d ke y sec o n dar y e n d p oi nts at t he 0. 0 5 le ve l (t w o-si de d), t he f oll o wi n g hierarc hi cal testi n g 
strate g y will be e m pl o ye d: 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 4 0  
A.  C o n d uct t he statistical testi n g f or t he pri mar y c o m paris o n bet wee n t he te na pa n or a n d 
place b o gr o u ps o n t he pri mar y e n d p oi nt “c h a n ge fr o m baseli ne i n s -P le vel at Wee k 
4” at t he si g nifica n ce le v el of 0. 0 5 (t w o -si de d). 
B.  If t he res ult of t he pri mar y c o m p aris o n o n t he pri mar y e n d p oi nt is p ositi ve (i.e., 
esti mate d mea n diff ere nt < 0 a n d p -v al ue ≤0. 0 5), t h e n c o n d uct t he statistical testi n g f or 
t he pri mar y c o m paris o n bet wee n t he t e na pa n or a n d place b o gr o u ps o n t he ke y 
sec o n dar y e n d p oi nt “s-P res p o nse at Wee k 4 ” at t he si g nifica nce le vel of 0. 0 5 (t w o -
si de d). 
C.  If t he res ult of t he pri mar y c o m p aris o n on “s - P res p o nse at Wee k 4” is p ositi ve (i.e., 
esti mate d rate diff er e nce > 0 a n d p - v al ue ≤0. 0 5), t h e n c o n d uct t he statistical testi n g f or 
t he f oll o wi n g t w o ke y s ec o n dar y e n d p oi nts usi n g t he H oc h ber g st e p- u p pr o ce d ure t o 
c o ntr ol t he fa mil y-wise T y p e I err or rate at t he si g nifica nce l e vel of 0. 0 5 (t w o -si de d): 
•  Relati ve c ha n ge fr o m bas eli ne i n i F G F 2 3 at Wee k 4  
•  Relati ve c ha n ge fr o m bas eli ne i n c F G F 2 3 at Wee k 4   
A nal ys es of ot her s ec o n d ar y e n d p oi nts will be des cri pti ve . No m ulti plicit y a dj ust me nt will be 
ma de f or t hes e a nal ys es.  
9. 4. 6  
H a n dli n g of Missi n g D at a  
I n t he c o m plete d cli nical st u d y T E N- 0 2- 2 0 1 c o n d u cte d b y Ar del y x, t he rate of missi n g s-P 
data was 6. 2 5 % ( 5/ 8 0) at b ot h Wee k 2 a n d Wee k 4 visits  d uri n g t he 4-wee k Ra n d o mize d 
Wit h dra wal Peri o d . T he r ate of missi n g s - P data d uri n g t he 4-wee k  D o u ble-Bli n d  Treat me nt 
Peri o d  i n t he c urre nt st u d y is e x pecte d t o be i n a si milar ra n ge. Th e missi n g s - P data d uri n g 
t he D o u ble- Bli n d  Treat m e nt Peri o d  is e x pecte d t o ha ve li mite d i m pact o n t he st u d y p o w er 
a n d t he acc urac y of esti mates  f or t he c urre nt st u d y.  
T he pri mar y e n d p oi nt, c h a n ge fr o m b aseli ne i n s- P le vel at Wee k 4, will be a nal yze d usi n g a n 
M M R M o n o bser ve d cas es of t he F A S . C ha n ges fr o m baseli ne i n s-P le vel at Wee k 1, 
Wee k  2, a n d Wee k 3 will als o be a nal yz e d usi n g t he sa me M M R M o n o bser ve d cas es. T o 
assess t he i m pact of missi n g s - P data o n t he pri mar y efficac y o utc o m es fr o m t he M M R M, 
se nsiti vit y a nal yses s uc h as A N C O V A  usi n g t he last- o bser vati o n-carrie d -f or war d ( L O C F) 
i m p utati o n a p pr oac h , c o m pleter a nal ysis, a n d ti p pi n g- p oi nt a nal ysis will be perf or me d. 
Details of t hese se nsiti vit y a n al ys es  will be pr o vi d e d i n t he S A P.  
F or o t her e n d p oi nts t o be a nal yze d usi n g A N O V A or A N C O V A a n d all bi nar y res p o ns e 
e n d p oi nts , missi n g data will be i m p ute d  usi n g t he L O C F a p pr o ac h  after a n al ysis.  


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 4 1  
Descri pti ve s u m maries of efficac y a n d safet y m eas ures will be base d o n o bser ve d dat a .    
9. 4. 7  
A dj ust me nts f or C o v ari ates  
I n ge ner al, t he t w o ra n d o mizati o n stratificati o n fact ors (t y p e of p h os p h ate bi n der a n d s-P 
le vel at Visit 3) will be a dj uste d i n  i nfere ntial a nal yses of efficac y e n d p oi nts . Detaile d 
i nf or mati o n o n c o variat e a dj ust me nt is pr o vi de d i n Secti o ns 9. 4. 3  a n d 9. 4. 4 .  
9. 4. 8  
Visit Wi n d o ws  
N o a nal ysis visit wi n d o ws will be f or mall y d efi ne d . T he sc he d ule of assess me nts a n d 
pr oce d ur es 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 . 
A n y a d diti o nal data c ollecte d bet wee n sc he d ul e d visits will be i ncl u de d i n s u bject data 
listi n gs b ut will be e x cl u de d fr o m statistical a nal yses, u nless t he a d diti o nal data is use d t o 
i m p ute missi n g data i n t he a nal ysis. 
9. 4. 9  
S af et y A n al yses 
Safet y a nal yses i ncl u d e s u m maries f or A Es , s afet y la b orat or y tests, vital si g ns, b o d y w ei g ht, 
1 2- lea d E C G, a n d p h ysical e x a mi nati o n.  
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 d v erse e v e nts ( T E 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 T E A Es.  
Ot her saf et y m eas ur es will be s u m marize d descri pti vel y b y treat me nt a n d visit . 
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 h e 
I n v esti gat or m ust i nf or m t he st u d y s u bject t hat his/ her st u d y -rel ate d rec or ds ma y b e 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 s u bject’s pri vac y of pers o n al 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 bilit y a n d Acc o u nta bilit y A ct of 1 9 9 6 
re g ulati o ns.  
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 d er 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 h e F D A o nl y if m ai ntai ne d i n c o nfi de nce b y t h e 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 nis he d t o hi m or her b y t h e S p o ns or a n d will 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 4 2  
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  
S p o ns or 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 n ce  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 u cte d a n d data are ge nerate d, d o c 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 u cte d i n acc or da n ce wit h t he pr o visi o ns of t he Declarati o n of H elsi 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 d e n 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 pecificall y, t his st u d y is base d o n 
a de q uatel y p erf or m e 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 o c ol re vie w e d b y a n I R B or I E C; t he st u d y will be c o n d u cte d b y scie ntifi call y 
a n d me dicall y q ualifie d p ers 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 w elfare of t he s u bjects 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 ot e ntial be nefits; a n d eac h s u bject will gi ve his or h er 
writte n, i nf or me d c o ns e nt bef ore a n y pr ot oc ol- dri ve n tests or e val uati o ns are perf or me d. 
T he I n vesti gat or ma y n ot de viate 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 b ee 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 x ce pt w he n necessar y t o 
eli mi nate i m me diate hazar ds t o t he s u bject or w h e 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 v e d b y t h e Me dical M o nit or a n d/ or Ar d el y x. 
A n y d e viati o n ma y res ult i n t he s u bject ha vi n g t o be wit h dra w n fr o m t he st u d y a n d m a y 
re n der t h at s u bject 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 he pr ot oc ol. A me n d me nts t o t he pr ot oc ol will be ma de o nl y 
after c o ns ult ati o n a n d a gr ee me nt bet w ee n t he S p o ns or, t he Me dical M o nit or, a n d 
I n v esti gat ors. All a me n d me nts t hat ha ve a n i m pact o n s u bject ris k or t he st u d y o bjecti ves, or 
re q uire r e visi o n of t he I C F, m ust recei ve a p pr o v al fr o m t he I R B pri or t o t heir 
i m ple me ntati o n. 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 4 3  
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 site m o nit or t o re vie w st u d y d ata as fre q ue ntl y as is dee m e d 
necessar y t o e ns ur e data are bei n g rec or de d i n a n a de q uate m a n ner a n d pr ot oc ol a d here n ce is 
satisfact or y. 
T he I n vesti gat or will pr o vi de access t o me dical rec or ds f or t he m o nit or t o verif y eC R F 
e ntries. T he I n v esti gat or is e x pecte d t o c o o perat e wit h t he S p o ns or or its desi g nee i n e ns uri n g 
t he st ud y a d h eres t o G C P re q uire me nts.  
T he I n vesti gat or ma y n ot recr uit s u bjects 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 visit at t he site t o c o n d uct a det aile d re vie w of t he pr ot oc ol a n d e C R F s a n d t he 
site has bee n acti vate d u p o n S p o ns or’s a p pr o val. Wit h a gree m e nt of t he S p o ns or, atte n da nce 
at a n In 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 priat e 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 pri atel 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 o cal r e q uire me nts as a p plica bl e.  
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 o c ol a me n d me nts (e x ce pt f or s p o ns or-a p pr o v e 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 m e nts a n d d oc u me nt 
u p dates, s u bject recr uit m e nt pr oce d ures, writte n i nf or mati o n t o be pr o vi de d t o t he s u bjects, 
a vaila ble safet y i n f or mati o n, i nf or mati o n a b o ut pa y m e nt a n d c o m pe nsati o n a vaila ble t o 
s u bjects, t he I n vesti gat or’s c urric ul u m vitae a n d/ or ot her e vi de n ce of q u alificati o ns, a n d a n y 
ot her d oc u me nts re q u este 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 bl e. 
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 s u bject ( or t he s u bject’s 
le gall y r es p o nsi ble s urr o gat e). S u bjects 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 


Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 4 4  
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 s u bject ( or 
g uar dia n), pri or t o a n y st u d y pr o ce 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  
Ele ctr o nic C ase Re p ort F o r ms  (e C R Fs) 
T he I n vesti gat or will be pr o vi de d wit h eC R Fs a n d will e ns ure all data fr o m s u bject 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 h e 
I n v esti gat or m ust si g n t h e e C R Fs t o veri f y t he i nt e 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 p art of t he 
d oc u me ntati o n t o be c ollate d pri or t o trial start . M e 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 ples 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 x a mi nati o n re p orts.  
1 3. 1. 3  
Rete nti o n of S o urce D o c u me nts  
T he I n vesti gat or m ust mai ntai n s o urce d o c 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 x a mi nati o n re p orts. 
1 3. 2  
Rete nti o n of Esse nti al D oc u me nts  
T he st u d y esse ntial d oc u me nts m ust be mai ntai ne d as s pecifie d i n t he I C H g ui deli nes t o 
a d here t o G C P a n d a p plica ble r e g ulat or y re q uire me nts. T he I n vesti gat or or i nstit uti o n s h o ul d 
ta ke meas ur es t o pre v e nt acci de nt al or pre mat ure d estr ucti o n of t hese d o c u me nts. 
Esse ntial d oc u me nts s h o ul d be retai ne d u ntil at least 2 years after t he l ast a p pr o val of a 
mar keti n g  a p plicati o n i n a n I C H re gi o n a n d u ntil t here are n o p e n di n g or c o nte m plate d 
mar keti n g a p plicati o ns i n a n I C H re gi o n or u ntil at least 2 years h a ve el a pse d si nce t he f or mal 
disc o nti n uati o n of cli nical de vel o p me nt of t he i n vesti gati o nal pr o d uct. T h es e d oc u me nts 
s h o ul d be retai ne d f or a l o n ger peri o d; h o w e ver, if re q uire d b y t he a p plica bl e re g ulat or y 
re q uire me nts or b y a n a gree me nt wit h t he S p o ns or. 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. 




Ar del y x, I nc.  
Pr ot oc ol N u m ber : T E N-0 2 -2 0 2  
E diti o n N o. 2 
 
2 2  J a n uar y 2 0 1 9 
C O N FI D E N TI A L  
P a ge 4 6  
1 6  
SI G N A T U R E S  
1 6. 1  
I n vesti g at or Si g n ature  
I a gree t o c o n d uct t he st u d y o utli ne d a b o v e 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 m e nts. All i nf or mati o n 
pertai ni n g t o t he st u d y will be treate d i n a c o nfi de ntial ma n ner.  
 
I n v esti gat or’s Si g n at ure   
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 
Date     
  
  
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