A Prospective, Multicenter, Phase -IV Study to Assess the Safety of Fixed Dose Combination of Dapagliflozin and Saxagliptin in Indian Type 2 Diabetes Mellitus (T2D) Patients
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Sponsor: AstraZeneca

1  (5 2 ) 
T his Cli nical St u d y Pr ot oc ol has bee n s u bject t o a peer re vie w acc or di n g t o Astra Ze neca 
Sta n dar d pr oce d ures .  T h e Cli nical St u d y Pr ot oc ol is p u blicl y re gistere d a n d t he res ults are 
discl ose d a n d/ or p u blis he d acc or di n g t o t he Astra Z e neca Gl o bal P olic y o n Bi oet hics a n d i n 
c o mplia nce wit h pre v aili n g la w s a n d re g ul ati o ns. 
Cli nic al St u d y Pr ot oc ol 
Dr u g S u bsta nce  
Da pa glifl ozi n + S a x a gli pti n  
St u d y C o de  
D 1 6 8 3 C 0 0 0 1 3  
Versi o n  
3. 0  
Date  
2 2  Se pte m ber  2 0 2 0  
A pr os pecti ve, m ultice nter, p h ase -I V st u d y t o assess t he s afet y of fi xe d d ose 
c o m bi n ati o n of d a p a glifl ozi n a n d s a x a gli pti n i n I n di a n T y pe 2 Di a betes 
Mellit us ( T 2 D) p atie nts . 
 
S p o ns or:  
Astr a Ze nec a P h ar m a I n di a Li mite d,  
Bl oc k N 1, 1 2t h Fl o or, M a n y at a E m b ass y B usi n
s P ar k 
R a c he n a h alli, O uter Ri n g R o a d, B a n g al ore 5 6 0 0 4 5  
R e d a ct e d f or P u bli c Di s cl o s ur e

2  (5 2 ) 
C LI NI C A L S T U D Y P R O T O C O L S Y N O P SI S  
 
A pr os pecti ve, m ultice nter, p h ase -I V st u d y t o assess t he s afet y of fi xe d d ose 
c o m bi n ati o n of d a p a glifl ozi n a n d s a x a gli pti n i n I n di a n T y pe 2 Di a betes 
Mellit us ( T 2 D) p atie nts . 
 
 
  
St u d y ce nters: A p pr o xi matel y 8 I n dia n ce ntres  are pla n ne d f or p artici pati o n  
N u m ber of S u bject s: 2 0 0 I n dia n T 2 D M  ( T y p e 2 Dia betes Mellit us) patie nt s 
1.  St u d y o bjecti ves  
a.  Pri m ar y o bjecti ve  
Pri m ar y O bjecti ve:  
O utc o me Me as ure:  
T o descri be t he a d verse e ve nts pr ofile of 
da pa glifl ozi n + sa xa gli pti n fi xe d d ose 
c o m bi nati o ns i n I n dia n T 2 D M patie nts.   
•  
A d verse 
E ve nts ( A Es) i ncl u di n g Seri o us 
a d verse e ve nts ( S A Es), 
A Es lea di n g t o 
disc o nti n uati o n ( D A E) a n d a d verse e ve nts of 
s pecial i nterest ( v ol u me de pleti o n, re nal 
eve nts,  
maj or  
h y p o gl ycae mic  
e ve nts, 
fract ures, uri nar y/ ge nital tract i nfecti o ns, 
dia betic 
ket oaci d osis , 
a m p utati o n s 
a n d 
h os pitalizati o n f or heart fail ure ) 
•  
Safet y la b orat or y val ues  
•  
Electr ocar di o gra m ( E C G)  
•  
Vital Si g ns ( p ulse a n d B P)  
•  
P h ysical e xa mi nati o n  
 
b.  Sec o n d ar y o bjecti ves  
Sec o n d ar y O bjecti ve:  
O utc o me Me as ure:  
T o descri be t he efficac y of da pa glifl ozi n + 
sa xa gli pti n fi xe d d ose c o m bi nati o n i n I n dia n 
T 2 D M patie nts  
•  
H b A 1c c ha n ge at wee k 2 4  c o m pare d t o 
baseli ne  
•  
Wei g ht c ha n ge at wee k 2 4  c o m pare d t o 
baseli ne  
•  
S yst olic Bl o o d Press ure ( S B P) c ha n ge at 
wee k 2 4 c o m pare d t o baseli ne   
•  
F P G  c ha n ge at wee k  2 4 c o m pare d t o baseli ne  

Cli nical St u d y Pr ot oc ol S y n o psis  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
3  (5 2 ) 
2.  S U B J E C T S E L E C TI O N, E N R O L M E N T, R A N D O MI S A T I O N, 
R E S T RI C TI O N S, DI S C O N TI N U A TI O N A N D WI T H D R A W A L  
Eac h s u bject s h o ul d meet all of t he i ncl usi o n criteria  a n d n o ne of t he e xcl usi o n criteria f or t his 
st u d y.  U n der n o cir c u msta nces ca n t here be e x ce pti o ns t o t his r ule. S u bjects will be recr uite d 
fr o m dia betes ma n a ge me nt ce nters u n der g ui da nce of pri nci pal i n vesti gat or after eli gi bilit y 
c hec k.  
a.  I ncl usi o n criteri a 
           F or i ncl usi o n i n t he st u d y s u bjects s h o ul d f ulfil t he f oll o wi n g criteri a: 
1.  Pr o visi o n of si g ne d a n d date d, writte n 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 acc or di n g t o l ocal I n dia n pr o ce d ure.  
2.  Male a n d fe male patie nts a ge d > 1 8 a n d a b o ve  
3.  D oc u me nte d hist or y of t y pe 2 dia bet es mellit us wit h H b A 1c le vel > 7. 0 % a n d ≤ 1 0 % at 
scree ni n g visit 
4.  Patie nts w h o are o n a st a ble d ose of a nti dia betic dr u gs  (i ncl u di n g o n Metf or mi n d ose 
bet wee n 1 0 0 0 -2 0 0 0 m g ) i n t he past 3 m o nt hs  
5.  Fe male s u bjects m ust be 1 yea r p ost-me n o pa usal, s ur gicall y sterile, or usi n g a n 
acce pta ble met h o d of c o n trace pti o n (a n acce pta bl e met h o d of c o ntr ace pti o n is defi ne d 
as a barrier met h o d i n c o nj u ncti o n wit h a s per mici de) f or t he d urati o n of t h e st u d y 
(fr o m t he ti me t he y si g n c o nse nt) t o pre v e nt pre g n a nc y. I n a d diti o n, or al 
c o ntrace pti ves, a p pr o ve d c o ntrace pti v e i m pla nt, l o n g -ter m i njecta ble c o ntrace pti o n, 
i ntra uteri ne de vic e, or t u bal li gati o n are all o we d. Oral c o ntrace pti o n al o n e is n ot 
acce pta ble; a d diti o nal barrier met h o ds i n c o nj u nct i o n wit h s per mici de m ust be use d. 
 
b.  E xcl usi o n criteri a  
1. K n o w n aller gies or  c o ntrai n dicati o n t o t he c o nt e nts of t he I P, da pa glifl o zi n or 
sa xa gli pti n ta blets. 
2.  Acti ve partici pati o n i n a n ot her cli nical st u d y wit h I P a n d/ or i n v esti gati o nal de vice  
3 . F or w o me n o nl y - c urre ntl y pre g na nt (c o nfir me d wit h p ositi ve pre g n a nc y test) or breast -
fee di n g. 
4. T y pe 1 dia betes mellit us.  
5. Treat me nt wit h a S G L T 2 i n hi bit or, G L P -1 a g o nist or D P P 4 i n hi bit ors at Visit 1 or 2  

Cli nical St u d y Pr ot oc ol S y n o psis  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
4  (5 2 ) 
6. Patie nts wit h m o derate t o se vere re nal i m pair me nt (e G F R p ersiste ntl y < 4 5 m L/ mi n/ 1. 7 3 
m 2 b y C K D -E PI  ( C hr o nic Ki d ne y Disease E pi de mi ol o g y C olla b orati o n) f or m ula or e n d -
sta ge re n al disease ( E S R D) or ‘ U nsta bl e or ra pi dl y pr o gressi n g re n al disease  
7 . Patie nts wit h se vere he patic i m pair me nt ( C hil d -P u g h class C)  
8 . Hist or y of  p a ncreatitis  or pa ncreatic s ur ger y  
9 . Patie nts wit h a hist or y of a n y mali g na nc y   
1 0 . Patie nts wit h a n y of t he f oll o wi n g C V/ Vasc ular Diseases wit hi n 3 m o nt hs pri or t o 
si g ni n g t he c o nse nt at e nr ol me nt, as assesse d b y t h e i n vesti gat or: 
• M y ocar dia l i nfarcti o n. 
• Car diac s ur g er y or re vas c ularizati o n ( C A B G/ P T C A).  
• U nsta ble a n gi na.  
• Tra nsie nt isc he mic attac k ( TI A) or si g nifica nt cere br o vasc ular dis ease.  
• U nsta ble or pre vi o usl y u n dia g n ose d arr h yt h mia.  
1 1. Hist or y of heart fail ure  
1 2. Se vere u n c o ntr olle d h y p erte nsi o n defi ne d as s yst olic bl o o d press ure ≥1 8 0 m m  H g 
a n d/ or diast olic bl o o d press ure ≥1 1 0 m m H g at a n y visit u p t o ra n d o misati o n  
1 3 . Hist or y of d ia betic ket oaci d osis  
1 4 . An y a c ute/c hr o nic s yste mic i nfecti o ns   
1 5 . Rec urre nt ur o ge nital i nfecti o ns 
1 6 . Patie nts at ris k f or v ol u me de pleti o n as j u d ge d b y t he i n vesti gat or 
1 7 . A n y c o n diti o n w hic h, i n t he j u d g me nt of t he I n vesti gat or, ma y re n d er t h e patie nt 
u na ble t o c o m plete t he st u d y or w hic h ma y p ose a si g nifica nt ris k t o t he patie nt or patie nt 
s us pecte d or wit h c o nfir me d p o or pr ot oc ol or me dicati o n c o m pli a nce  
 
D ur ati o n of tre at me nt  
T his is a 2 4 wee k  o p e n la bel si n gle ar m pr os pecti ve  st u d y t o c haracteri ze  safet y of Da p a/ Sa xa , 
1 0 m g/ 5  m g  fi xe d d ose c o m bi nati o n i n I n dia n T 2 D M patie nts.   
Dr u g n a me , d os a ge a n d mo de of a d mi nistr ati o n  
Patie nts will be gi ve n o nce  dail y fi xe d d ose c o m bi nati o n of Da pa/ Sa xa 1 0 
m g/ 5  m g  
a d mi nistere d orall y at t he sa me ti me of t he da y t hr o u g h o ut t he st u d y.  E ver y atte m pt s h o ul d be 
ma de t o mai ntai n patie nts o n desi g nate d t hera p y f or 2 4 wee ks  of st u d y d urati o n.  
Ot her Me dici nal pr o d u cts:  

Cli nical St u d y Pr ot oc ol S y n o psis  
Dr u g S u bsta nce Da pa glifl ozi n + S a xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
5  (5 2 ) 
Patie nt will c o nti n ue recei vi n g me dici nes ot her t ha n st u d y dr u g as per i n vesti gat ors discreti o n. 
Patie nt ma y be eli gi ble t o recei ve a d diti o nal gl uc ose l o weri n g dr u g if h e meets res c ue criteria 
as details pr o vi de d i n resc ue t hera p y s ecti o n.  S p o ns or will n ot pr o vi de a n y ot her me dici ne 
e xce pt i n vesti gati o n al pr o d uct Da pa/ Sa xa  1 0  m g/ 5  m g.    
St atistic al met h o ds  
T he pri mar y o bje cti ve of t he st u d y is t o  c haracterize  t he safet y of fi xe d d ose c o m bi nati o n of 
Da pa/ Sa xa  1 0 m g/ 5  m g  i n I n dia n T 2 D M patie nts. T his is a re g ulat or y re q uire me nt t o esta blis h 
t hat F D Cs are safe w he n use d i n c o m bi nati o n i n a d diti o n t o t he data a vaila ble o n i n di vi d ual 
c o m p o ne nts. As per t he cli nical data,  base d o n i n v esti gat or’s assess me nt  i n ci de nce of a d verse 
e ve nts  relat e d t o F D C
 
  
N u m ber a n d p erce nta ges of I nci de n ce of a d verse e ve nts will be prese nte d , stratifie d b y 
a ge/ ge n der/ baseli ne me di cati o ns. A n n ualise d e v e nt rate s hal l als o be prese nte d i n a d diti o n t o 
t he i nci de nce rate d uri n g t he st u d y. Mea n c ha n g e i n H b A 1 C fr o m baseli ne t o 6 m o nt hs f or 
patie nts will be a nal yse d usi n g paire d t test / Wilc o x o n si g ne d -ra nk test at 5 % le vel of 
si g nifica nce. 
MI L E S T O N E S  
 
Esti mate d date of first patie nt i n 
Dece m ber  2 0 2 0  
Esti mate d date of last patie nt i n  
Se pte m ber  2 0 2 1  
Esti mate d date of last patie nt last visit  
A pril  2 0 2 2  
Esti mate d date of data base l oc k  
J u ne 2 0 2 2  
Cli nical s t u d y re p ort pre parati o n a n d s u b missi o n 
A u g ust  2 0 2 2  
 
 
C CI

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
6  (5 2 ) 
T A B L E O F C O N T E N T S  
P A G E  
 
TI T L E P A G E  ........................................................................................................... 1  
C LI NI C A L S T U D Y P R O T O C O L S Y N O P SI S  ....................................................... 2  
T A B L E O F C O N T E N T S  ......................................................................................... 6  
1.  
I N T R O D U C TI O N ................................................................................................. 1 1  
1. 1  
Bac k gr o u n d a n d rati o nal e f or c o n d u cti n g t his st u d y  ............................................. 1 1  
1. 2  
Rati o nale f or st u d y desi g n, d oses a n d c o ntr ol gr o u ps  ............................................ 1 2  
1. 3  
Be nefit/ris k a n d et hical asses s me nt........................................................................ 1 2  
1. 4  
St u d y Desi g n  .......................................................................................................... 1 3  
2.  
S T U D Y O BJ E C TI V E S  .......................................................................................... 1 4  
2. 1  
Pri mar y o bjecti ve  ................................................................................................... 1 4  
2. 2  
Sec o n dar y o bje cti ves  ............................................................................................. 1 4  
2. 3  
Safet y o bjecti ves  .................................................................................................... 1 4  
3.  
S U BJ E C T S E L E C TI O N, E N R O L M E N T, R A N D O MI S A T I O N, 
R E S T RI C TI O N S, DI S C O N TI N U A TI O N A N D WI T H D R A W A L  ...................... 1 4  
3. 1  
I n cl usi o n criteria .................................................................................................... 1 5  
3. 2  
E xcl usi o n criteria  ................................................................................................... 1 5  
3. 3  
S u bject e nr ol me nt a n d ra n d o mizati o n  ................................................................... 1 6  
3. 4  
Pr oce d ures f or ha n dli n g i nc orrectl y e nr olle d or ra n d o mize d s u bjects  ................... 1 6  
3. 5  
Restricti o ns  ............................................................................................................ 1 7  
3. 6  
Disc o nti n uati o n of i n vesti gati o nal pr o d uct  ............................................................ 1 7  
3. 7  
Criteria f or wit h dr a wal  ........................................................................................... 1 8  
3. 7 . 1 
Scree n fail ures  ........................................................................................................ 1 8  
3. 7 . 2 
Wit h dra wal of t h e i nf or me d c o nse nt  ...................................................................... 1 9  
3. 8  
Disc o nti n uati o n of t he st u d y  .................................................................................. 1 9  
4.  
S T U D Y P L A N A N D TI MI N G O F P R O C E D U R E S  ............................................. 1 9  
4. 1  
Scree ni n g/ E nr ol me nt peri o d  .................................................................................. 2 1  
4. 2  
Treat me nt peri o d  .................................................................................................... 2 1  
4. 3  
F oll o w -u p peri o d  .................................................................................................... 2 1  
5.  
S T U D Y A S S E S S M E N T S  ..................................................................................... 2 1  

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
7  (5 2 ) 
5. 1  
Efficac y assess me nts  .............................................................................................. 2 1  
5. 2  
Safet y assess me nts  ................................................................................................. 2 2  
5. 3  
Ot her assess me nts  .................................................................................................. 2 3  
6.  
S A F E T Y R E P O R TI N G A N D  M E DI C A L M A N A G E M E N T  .............................. 2 7  
6. 1  
Defi niti o n of a d vers e e v e nts  .................................................................................. 2 7  
6. 2  
Defi niti o ns of seri o us a d verse e v e nt  ...................................................................... 2 7  
6. 3  
Rec or di n g of a d v erse e ve nts  .................................................................................. 2 7  
6. 3. 1  
Ti me peri o d f or c ollecti o n of a d verse e ve nts  ......................................................... 2 7  
6. 3. 2  
F oll o w -u p of u nres ol ve d a d verse e ve nts  ................................................................ 2 8  
6. 3. 3  
Varia bles  ................................................................................................................ 2 8  
6. 3. 4  
Ca usalit y c ollecti o n  ................................................................................................ 2 9  
6. 3. 5  
A d verse e ve nts base d o n si g ns a n d s y m pt o ms ....................................................... 2 9  
6. 3. 6  
A d verse e ve nts base d o n e xa mi nati o ns a n d tests  ................................................... 2 9  
6. 4  
Re p orti n g of seri o us a d v erse e v e nts ....................................................................... 3 0  
6. 5  
O ver d ose  ................................................................................................................ 3 0  
6. 6  
Pre g na nc y  ............................................................................................................... 3 0  
6. 6. 1  
Mater nal e x p os ure  .................................................................................................. 3 1  
6. 7  
Me dicati o n Err or  .................................................................................................... 3 1  
7.  
I N V E S TI G A TI O N A L P R O DU C T A N D O T H E R T R E A T M E N T S  .................... 3 2  
7. 1  
I d e ntit y of i n vesti gati o nal pr o d uct(s) ..................................................................... 3 2  
7. 2  
D ose a n d treat me nt re gi me ns  ................................................................................. 3 3  
7. 3  
La belli n g  ................................................................................................................ 3 3  
7. 4  
St ora ge  ................................................................................................................... 3 3  
7. 5  
C o m plia nce  ............................................................................................................ 3 3  
7. 6  
Acc o u n ta bilit y ........................................................................................................ 3 3  
7. 7  
C o nc o mita nt a n d ot her tr eat me nts  ......................................................................... 3 3  
7. 7. 1  
Ot her c o nc o mita nt tr eat me nt  .................................................................................. 3 4  
8.  
S T A TI S TI C A L A N A L Y S E S  B Y A S T R A Z E N E C A  ............................................ 3 4  
9.  
S T U D Y A N D D A T A M A N A G E M E N T B Y A S T R A Z E N E C A  .......................... 3 5  
9. 1  
Trai ni n g of st u d y site staff  ..................................................................................... 3 5  
9. 2  
M o nit ori n g of t he st u d y  ......................................................................................... 3 5  
9. 2. 1  
S o urc e data  ............................................................................................................. 3 6  
9. 2. 2  
St u d y a gree me nts  ................................................................................................... 3 6  
9. 2. 3  
Arc hi vi n g of st u d y d oc u me nts  ............................................................................... 3 6  
9. 3  
St u d y ti meta ble a n d e n d of st u d y  ........................................................................... 3 6  

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
8  (5 2 ) 
9. 4  
Data ma na g e me nt b y Astra Ze n eca  ....................................................................... 3 6  
1 0.  
E T HI C A L A N D R E G U L A T O R Y R E Q UI R E M E N T S  ......................................... 3 7  
1 0. 1  
Et hical c o n d uct of t he st u d y  ................................................................................... 3 7  
1 0. 2  
S u bject data pr ote cti o n  ........................................................................................... 3 7  
1 0. 3  
Et hics a n d re g ulat or y re vie w .................................................................................. 3 7  
1 0. 4  
I nf or me d c o ns e nt ................................................................................................... 3 8  
1 0. 5  
C ha n ges t o t he Cli nical St u d y Pr ot oc ol a n d I nf or m e d C o nse nt F or m  ................... 3 8  
1 0. 6  
A u dits a n d i ns pecti o ns  ........................................................................................... 3 9  
1 1.  
LI S T O F R E F E R E N C E S  ....................................................................................... 4 0  
1 2.  
SI G N A T U R E S  ....................................................................................................... 4 8  
 
 
LI S T O F T A B L E S  
Ta ble 1  
St u d y Pla n detaili n g t he pr oce d ures  ......................................................... 1 9  
Ta ble 2  
La b orat or y Safet y Varia bles  ..................................................................... 2 2  
 
LI S T O F FI G U R E  
Fi g ure 1  
St u dy fl o w c h art  ....................................................................................... 1 3  
 
LI S T O F A P P E N DI C E S  
A p pe n di x A  
A d diti o nal  Safet y I nf or m ati o n  .................................................................. 4 1  
A p pe n di x B  
Acti o ns Re q uire d i n Cases of I ncreas es i n Li ver Bi oc he mistr y a n d 
E val uati o n of H y’s La w  ............................................................................ 4 3  

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
9  (5 2 ) 
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N O F T E R M S  
T he f oll o wi n g a b bre vi ati o ns a n d s pecial ter ms are use d i n t his st u d y Cli nical St u d y Pr ot oc ol.  
 
A b bre vi ati o n or 
s peci al ter m 
E x pl a n ati o n  
 
 
A E  
A d verse E ve nt  
A L P                      
Al kali ne p h os p hatase  
A S T  
As partate a mi n otra nsferase  
B MI  
B o d y Mass I n de x  
C A B G/ P T C A  
c or o nar y arter y b y pass grafti n g/ perc uta ne o us tra nsl u mi nal c or o nar y 
a n gi oplast y  
C K  
Creati ne ki nase  
C R F  
Case Re p ort F or m (electr o nic/ pa per)  
C S A  
C li nical St u d y A gree me nt 
C S R  
Cli nical St u d y Re p ort  
D A E  
Disc o nti n uati o n of I n vesti gati o nal Pr o d uct d ue t o A d verse E ve nt  
D K A  
Dia betic ket oaci d osis  
E C  
Et hics C o m mittee, s y n o n y m o us t o I nstit uti o nal Re vie w B oar d (I R B) a n d 
I n de pe n de nt Et hics C o m mittee (I E C)  
E C G  
Electr ocar di o gra m  
e G F R 
Esti mate d Gl o mer ular Filtrati o n  
E S R D  
E n d Sta ge Re nal Disease  
F B G  
Fasti n g Bl o o d Gl uc ose  
F D C  
Fi xe d D ose C o m bi nati o n  
F P G  
Fasti n g Plas ma Gl uc ose  
G C P  
G o o d Cli nical Practice  
H b  
He m o gl o bi n  
H b A 1c  
Gl ycate d hae m o gl o bi n  
I C H 
I nter nati o nal C o nfere nce o n Har m o nisati o n 
I nter nati o nal 
C o or di nati n g 
i n vesti gat or 
If a st u d y is c o n d ucte d i n se veral c o u ntries t he I nter nati o nal C o or di nati n g 
I n vesti gat or is t he I n vesti gat or c o or di nati n g t he i n vesti gat ors a n d/ or 
acti vities i nter nati o nall y.  

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
1 0  (5 2 ) 
A b bre vi ati o n or 
s peci al ter m 
E x pl a n ati o n  
I P 
I n vesti gati o nal Pr o d uct  
I V R S 
I nteracti ve V oice Res p o nse S yste m 
I W R S 
I nteracti ve We b Res p o nse S yste m  
LI M S  
La b orat or y I nf or mati o n Ma na ge me nt S yste m  
L S L V  
Last S u bject Last Visit  
N Y H A  
Ne w Y or k Heart Ass ociati o n  
O A E  
Ot her Si g nifica nt A d verse E ve nt  
PI  
Pri nci pal I n vesti gat or  
P P G  
P ost pra n dial Gl uc ose  
S A E  
Seri o us A d verse E ve nt  
S B P  
S yst olic Bl o o d Press ure  
S G L T  
S o di u m Gl uc ose C o tra ns p orter  
S U  
S ul p h o n yl urea  
T 2 D M  
T y pe 2 Dia betes  Mellit us  
TI A  
Tra nsie nt Isc he mic Attac k  
U P T  
Uri ne Pre g na nc y Test  
U TI  
Uri nar y Tract I nfecti o n  
 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
1 1  (5 2 ) 
1.  I N T R O D U C TI O N 
1. 1   B ac k gr o u n d a n d r ati o n ale f or c o n d ucti n g t his st u d y  
Dia betes is n o w  a n e n demic t o I n dia wit h a n esti mate d 7 2. 9  milli o n I n dia ns li vi n g wit h t h is 
c o n diti o n a n d c urre ntl y at sec o n d p ositi o n after C hi na i n w orl d. ( 1) Metf or mi n is u se d as 1st li ne 
oral a nti - dia betic dr u g i n m ost cases. S ulf o n yl ure as ( S U) are use d as fre q u e nt first a d d -o n after 
fail ure of metf or mi n m o n ot hera p y.( 2) A p pr o xi mat el y 6 7 % patie nts fail t o ac hie ve  < 7 % H b A 1 c 
g oal. ( 3) T his  e m p h asise nee d f or ne wer tr eat me nt o pti o ns. S o di u m Gl uc ose C o -tra ns p orter 2 
( S G L T 2) i n hi bit ors are a ne wer class of t hera p y w hic h has a l o wer i nci de n ce of h y p o gl y cae mia 
a n d i n a d diti o n hel ps i n wei g ht a n d B P re d ucti o n. Sa xa gli pti n is a D P P ( Di pe pti d yl Pe p ti dase)-
4 i n hi bit or. T he sai d F D C are a p pr o ve d w orl d wi de basis a vai la ble data o n st u d y d o ne wit h 
i n di vi d ual c o m p o ne nts.  L ocal Healt h A ut h ority  i n I n di a has ma n date d t o s u b mit cli nical data 
o n F D C p ost  mar keti n g a ut h orizati o n e ve n if i n di vi d ual c o m p o ne nts are a p pr o ve d f or us e. T his 
st u d y is a d dressi n g t his u n met nee d t o ge nerate l o cal data o n F D C i n I n dia n T 2 D M patie nts.  
 
Da pa glifl ozi n ( mar kete d u n der t he tra de na me F O R XI G A ® ) is a re versi bl y-c o m petiti ve, hi g hl y 
selecti ve a n d orall y acti ve i n hi bit or of S G L T 2, t he maj or tra ns p orter res p o nsi ble f or re nal 
gl uc ose rea bs or pti o n.  Da pa glifl ozi n’s 
mec ha nis m 
of acti o n is 
differe nt fr o m, a n d 
c o m ple me ntar y t o, t he  m ec ha nis ms of acti o n of c urre ntl y a vaila bl e dia betic  me dici nes, res ulti n g 
i n t he direct a n d i ns uli n-i n de pe nde nt eli mi nati o n of gl uc ose b y t he ki d ne y. ( 4) F urt her, as 
S G L T 2 is al m ost  e xcl usi vel y e x presse d i n t he ki d ne y, t he hi g hl y selecti ve nat ure of 
da pa glifl ozi n mi ni mi zes t he ris k of off tar get (ie, n o n-ki d ne y) effects. As  s uc h, da pa glifl ozi n 
offers a n i m p orta nt a d diti o nal  strate g y f or i m pr o vi n g gl ycae mic c o ntr ol i n p atie nts wit h T 2 D M. 
 
Sa xa gli pti n is a hi g hl y p ote nt, selecti ve, re v ersi ble, a n d c o m petiti ve D P P -4 i n hi bit or. B y 
i n hi biti n g D P P-4, sa xa gli pti n p ote ntiates acti ve  e n d o ge n o us G L P -1 c o nce ntrati o ns, a u g me nti n g 
t he p h ysi ol o gical mec h a nis m of i ns uli n secreti o n a n d s u p pressi n g gl uca g o n release, t here b y 
re d uci n g P P G a n d F P G le vels i n patie nts wit h T 2 D. Sa xa gli pti n is a p pr o ve d b y t he U S a n d E U 
f or t he treat me nt of T 2 D a n d i n P hase III trials, has effecti vel y re d uce d H b A 1c i n patie nts wit h 
i na de q uatel y c o ntr olle d T 2 D o n a sta ble d os e of metf or mi n, S Us, or t hiaz oli di ne di o ne, a n d has 
fa v ora bl e safet y a n d t olera bilit y pr ofiles.( 5) 
 
Q T E R N ® (da pa glifl ozi n/ s a xa gli pti n) c o m bi nes da pa glifl ozi n a n d sa x a gli ptin i n a fi xe d -d ose 
c o m bi nati o n ta blet desi g ne d t o be a d mi nistere d o nce dail y . T he c o m bi nati o n of t hese dr u gs, 
wit h c o m ple me ntar y mec ha nis m of acti o ns, a n d wit h  cli nicall y i m p orta nt effects o n H b A 1c, 
F B G , P P G a n d wei g ht l oss, is e x pecte d t o f or m a cli nicall y rele va nt para di g m f or ac hi e vi n g a n d 
mai ntai ni n g gl ycae mic c o ntr ol i n patie nts w h o  h a ve diffi c ult y wit h mai ntai ni n g gl ycae mic 
c o ntr ol o n diet/lifest yle, metf or mi n al o ne, or i n c o m bi nati o n  wit h o t her oral a nti dia betic dr u gs 
or i ns uli n. Q T E R N  is i n dicate d as a n a dj u n ct t o diet a n d e xercise i n patie nts w h ose gl yce mic 
c o ntr ol is i na de q uate wit h da pa glifl ozi n or w h o are alrea d y treate d wit h da pa glifl ozi n a n d 
sa xa gli pti n.( 6) 
 
A n F D C pr o d uct c o m bi ni n g da pa glifl ozi n a n d sa xa gli pt i n has t he p ote ntial f or pr o vi di n g 
patie nts wit h T 2 D M wit h a ne w tr eat me nt o pti o n t hat ma y i m pr o ve c o m plia nce b y re d uci n g 
ta blet b ur de n t ha n t he i n di vi d ual ta blets a d mi nistere d se paratel y.( 7) 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
1 2  (5 2 ) 
 
1. 2  R ati o n ale f or st u d y desi g n, d oses a n d c o ntr ol gr o u ps  
T his st u d y is desi g ne d t o ge nerat e l ocal I n dia n safet y e vi de nce f or Da pa/ Sa x a  1 0 m g/ 5  m g  F D C  
as per l ocal healt h re g ulat or y re q uest. B ot h d a pa glifl ozi n a n d sa xa gli pti n are a p pr o ve d i n I n dia 
f or cli nic al use as i n di vi d ual t hera py f or ma na gi n g T 2 D M patie nts. T his st u d y is t o pr o vi de 
safet y data w he n b ot h m olec ules are a dmi nistere d as F D C f or m ulati o n. T his is a si n gle ar m 
st u d y a n d n o c o ntr ol gr o u p is pla n ne d.  
1. 3  Be nefit/ris k a n d et hic al assess me nt  
 
Ris k c ate g or y  
C o nsi deri n g sa xa g li pti n a n d da p a glifl ozi n’s 
m ec ha nis m of acti o n, t h e pre vi o us cli nical 
e x perie n ce wit h b ot h m olec ules, t he st u d y’s desi g n feat ures (i n cl u di n g t he i ncl usi o n, e xcl usi o n, 
a n d is c o nti n uati o n criteria), a n d t he pla n ne d safet y pr oce d ures, p artic i p ati o n i n t his st u d y 
prese nts a mi ni mal a n d t h us acce pta ble ris k t o t he i n di vi d ual s u bjects t hat will be i n cl u de d. 
Da pa glifl ozi n a n d s a xa gli pti n b ot h ha ve gl o bal a n d I n dia n mar ket a p pr o val a n d ha v e bee n 
a d mi nistere d t o t h o usa n ds of T 2 D M patie nts.  
P ote nti a l Ris k 
T he safet y a n d efficac y of t he 1 0 m g da pa glifl ozi n/ 5 m g sa xa gli pti n fi xe d -d ose c o m bi nati o n 
was e v al ua te d i n t hr ee p hase 3, ra n d o mise d, d o u ble-bli n d, acti ve/ place b o -c o ntr olle d cli nical 
trials i n 1 1 6 9 a d ult s u bjects wit h t y pe 2 dia betes mellit us. O ne trial wit h sa xa gli pti n a n d 
da pa glifl ozi n a d de d c o n c o mita ntl y t o metf or mi n was c o n d ucte d f or 2 4 wee ks. T w o a d d -o n 
t hera p y trials, w hic h a d d e d eit her da p a glifl ozi n t o sa xa gli pti n pl us metf or mi n or sa xa gli pti n t o 
da pa glifl ozi n pl us metf or mi n, were als o c o n d uc te d f or 2 4 wee ks f oll o we d b y a 2 8 wee k 
e xte nsi o n treat me nt peri o d. T he safet y pr ofile of t he c o m bi ne d use of sa xa gli pti n a n d 
da pa glifl ozi n i n t hese tri als f or u p t o 5 2 wee ks was c o m para ble t o t he s afet y pr ofiles f or t he 
m o n o -c o m p o ne nts.  
Patie nts at ris k f o r v ol u me de pleti o n d ue t o c o-e xisti n g c o n diti o ns or c o nc o mita nt me dicati o ns, 
s uc h as l o o p di uretics s h o ul d ha ve caref ul m o nit ori n g of t heir v ol u me stat us, as j u d ge d b y t he 
i n vesti gat or.  
I n a d diti o n, all s u bjects will c o nti n ue ta ki n g si milar d ose of t heir a nti dia betic me dicati o ns.  
N o st u d y pr oce d ure will p ut s u bjects at a ris k be y o n d t h ose or di naril y e nc o u ntere d d uri n g t he 
perf or ma n ce of r o uti ne me dical e xa mi nati o ns or r o uti ne tests.  
P ote nti al be nefits t o s u bjects  
All s u bjects will recei ve acti ve a nti h y per gl yce mic t hera p y of da pa glifl ozi n /sa xa gli pti n as fi xe d 
d ose c o m bi nati o n; gl o bal st u dies ha ve esta blis he d t h e t he ris k -b e nefit pr ofil e f or t he i n di vi d ual 
c o m p o ne nts, b ut t he safet y f or t he fi xe d d ose c o m bi nati o n ne e ds t o be c o nfir me d i n a n I n dia n 
p hase I V st u d y. I n t his st u d y, t he d oses of Da p a/ Sa xa 1 0 m g/ 5 m g F D C was c h ose n t o pr o vi de 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
1 3  (5 2 ) 
effic ac y i n re d uci n g h y p er gl yce mia w hile miti gati n g t he p ote ntial f or A Es, base d o n pre vi o us 
cli nical e x perie n ce. I n a d diti o n, da pa g lifl ozi n decrease b o d y wei g ht ( or pre ve nt wei g ht gai n) as 
well as l o wer bl o o d press ure ( B P) es peciall y i n s u bjects wit h ele vate d baseli ne B P.  
S u bject s are als o e x p ect e d t o recei ve be n efit i n t he f or m of i ncreas e d me dical care/atte nti o n 
w he n partici p ati n g i n st u d y pr oce d ures, w hic h i ncl u des at least 4  cli nic visits wit h at least 4  
p h ysical e xa mi nati o ns o v er t he 2 4 -wee k  st u d y. 
I nf or me d c o nse nt  
All pr os p ecti ve partici p a nts will be f ull y i nf or me d of t he p ossi ble ris ks a n d be nefits ass ociat e d 
wit h  t his st u d y, a n d t heir writte n c o nse nt will be recei ve d pri or t o p erf or mi n g a n y st u d y -
relate d acti vit y.  
S u bjects are free t o wit h dra w fr o m t he st u d y at a n y ti me ( i n vesti gati o nal pr o d uct a n d f urt her 
assess me nts), wit h o ut pr ej u dice t o f urt her treat me nt.  
 
1. 4   St u d y Desi g n  
T his is  a pr os pecti ve, m ultice nter, p hase -I V st u d y t o assess t he safet y of fi xe d d ose c o m bi nati o n 
of da pa glifl ozi n a n d s a xa gli pti n i n I n dia n T y pe 2 Dia betes Mellit us ( T 2 D) patie nts . 
Fi g ure 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Visit  
1  
 
 
 
        2  
 
 
3 ( T C)  
4 ( T C)  
 
        5  
 
6 ( T C)  
 
7  
 
8 ( T C)  
 
9  
1 0  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Wee k 
Da y  
-1  
0  
1  
4  
8  
1 2  
1 6  
2 0  
2 4  
2 6  
 
( ± 5) 
( ± 5) 
( ± 2) 
( ± 2) 
( ± 5) 
( ± 2) 
( ± 5) 
( ± 2) 
( + 5) 
( + 2) 
 
E  
 
 
 
 
 
 
 
E O T        E O S  
Da pa glifl ozi n 1 0 m g a n d Sa xa gli pti n 5 m g Fi xe d D ose 
C o m bi nati o n  

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
1 4  (5 2 ) 
2  S T U D Y O B J E C TI V E S  
2 . 1 Pri m ar y o bjecti ve  
Pri m ar y O bjecti ve:  
O utc o me Me as ure:  
T o descri be t he a d verse e ve nts pr ofile of 
da pa glifl ozi n + sa xa gli pti n fi xe d d ose 
c o m bi nati o ns i n I n dia n T 2 D M patie nts  at 24 
wee ks .   
•  
A d verse 
E ve nts ( A Es) 
i ncl u di n g Seri o us 
a d verse e ve nts ( S A Es), 
A Es lea di n g t o 
disc o nti n uati o n ( D A E) a n d   a d verse e ve nts of 
s pecial i nterest ( v ol u me de pleti o n, re nal 
e ve nts,  
maj or  
h y p o gl ycae mic 
e ve nts, 
fract ures, uri nar y/ ge nital tract i nfecti o ns  
d ia betic 
ket oaci d osis, 
a m p utati o n s 
a n d 
h os pitalizati o n f or heart fail ure ) 
•  
Safet y la b orat or y val ues  
•  
Electr ocar di o gra m ( E C G)  
•  
Vital Si g ns ( p ulse a n d B P)  
•  
P h ysical e xa mi nati o n  
 
2. 2   Sec o n d ar y o bjecti ves  
Sec o n d ar y O bjecti ve:  
O utc o me Me as ure :  
T o descri be t he efficac y of da pa glifl ozi n + 
sa xa gli pti n fi xe d d ose c o m bi nati o n i n I n dia n 
T 2 D M patie nts  at 2 4 wee ks 
•  
H b A 1c c ha n ge at wee k 2 4  c o m pare d t o 
baseli ne  
•  
W ei g ht c ha n ge at wee k 2 4  c o m pare d t o 
baseli n e 
•  
S yst olic Bl o o d Press ure ( S B P) c ha n ge at 
wee k 2 4  c o m pare d t o baseli ne   
•  
F P G  c ha n ge at wee k 2 4 c o m pare d t o baseli ne  
2. 3   S afet y o bjecti ves  
See secti o n 2. 1  
3  S U B J E C T  S E L E C TI O N, E N R O L M E N T, R A N D O MI S A TI O N, 
R E S T RI C TI O N S, DI S C O N TI N U A TI O N A N D WI T H D R A W A L  
 
Eac h s u bject s h o ul d meet all of t he i ncl usi o n criteria a n d n o n e of t he e x cl usi o n cr iteria f or t his 
st u d y.  U n der n o circ u msta nces ca n t here be e xce pti o ns t o t his r ule.  S u b jects will be recr uite d 
fr o m dia bet es ma n a ge m e nt ce nt ers u n d er g ui d a nce of pri nci p al i n vesti g at or after eli gi bilit y 
c hec k.  

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
1 5  (5 2 ) 
3. 1   I ncl usi o n criteri a 
F o r i ncl usi o n i n t he st ud y s u bjects s h o ul d f ulfil t he f oll o wi n g criteria: 
1.  Pr o visi o n of si g ne d a n d date d, writ te n i nf or m e d c o ns e nt pri or t o a n y st u d y s pecific 
pr oce d ures acc or di n g t o l ocal I n dia n pr o ce d ure.  
2. Male a n d f e male patie nts a ge d > 1 8 a n d a b o ve  
3.  D oc u me nte d hist or y o f t y pe 2 dia betes mellit us wit h H b A1c le vel > 7. 0 % a n d ≤ 1 0 % at 
scree ni n g visit 
4. Patie nts w h o are o n a sta ble d ose of a nti dia betic dr u gs  (i ncl u di n g o n Metf or mi n d ose 
bet wee n 1 0 0 0 -2 0 0 0 m g )   i n t he past 3 m o nt hs  
5. Fe male s u bjects m ust be 1 year p ost -me n o p a us al, s ur gicall y sterile, or usi n g a n acce pta ble 
met h o d of c o ntrace pti o n (a n acce pta ble met h o d of c o ntrace pti o n is defi ne d as a barri er 
met h o d i n c o nj u ncti o n wit h a s per mici de) f or t h e d urati o n of t he st u d y (fr o m t he ti me t he y 
si g n c o nse nt) t o pre ve nt preg na nc y. I n a d diti o n, oral c o ntrace pti ves, a p pr o ve d c o ntrace pti ve 
i m pla nt, l o n g-term i njecta ble c o ntrace pti o n, i ntra uteri ne de vice, or t u bal li gati o n are 
all o we d. 
Oral c o ntrace pti o n al o ne is n ot acce pta ble; a d diti o nal b arrier 
met h o ds i n 
c o nj u ncti o n wit h s pe r mici de m ust be use d. 
 
3. 2   E xcl usi o n criteri a  
1. K n o w n aller gies or c o ntrai n dicati o n  t o t he c o nte nts of t he I P, da pa glifl ozi n or sa xa gli pti n 
ta blets. 
 
2.   Acti ve partici pati o n i n a n ot her cli nical st u d y wit h I P a n d/ or i n v esti gati o nal de vice  
3. F or w o me n o nl y - curre ntl y pre g na nt (c o nfir me d wit h p ositi ve pre g n a nc y test) or breast -
fee di n g. 
4. T y pe 1 dia betes mellit us.  
5. Treat me nt wit h a S G L T 2 i n hi bit or, G L P -1 a g o nist or D P P 4 i n hi bit ors at Visit 1 or 2  
6 . Patie nts wit h m o derate t o se vere re nal i m pair me nt (e G F R persiste ntl y < 4 5 m L/ mi n/ 1. 7 3 
m 2 b y C K D -E PI f or m ula, or e n d-sta ge re nal disease ( E S R D) or ‘ U nst a ble or ra pi dl y 
pr o gressi n g re n al disease  
7 . Patie nts wit h se vere he patic i m pair me nt ( C hil d-P u g h class C ) 
8 . Hist or y of  p a ncreatitis  or pa ncreatic s ur ger y  

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
1 6  (5 2 ) 
      9 . Pa tie nts wit h a hist or y of a n y mali g na nc y  
1 0 . Patie nts wit h a n y of t he f oll o wi n g C V/ Vasc ular Diseases wit hi n 3 m o nt hs pri or t o 
si g ni n g t he c o nse nt at e nr ol me nt, as assesse d b y t h e i n vesti gat or: 
• 
M y ocar dial i nfarcti o n.  
• 
Car diac s ur g er y or re vas c ularizati o n ( C A B G/ P T C A).  
• 
U nsta ble a n gi na.  
• 
Tra nsie nt isc he mic attac k ( TI A) or si g nifica nt cere br o vasc ular dis ease.  
• 
U nsta ble or pre vi o usl y u n dia g n ose d arr h yt h mia.  
     1 1. Hist or y of heart fail ure  
     1 2. Se vere u n c o ntr olle d h y perte nsi o n defi ne d as s yst olic bl o o d press ur e  ≥1 8 0 m m H g 
a n d/ or diast olic bl o o d press ure ≥1 1 0 m m H g at a n y visit u p t o ra n d o misati o n  
      1 3. Hist or y of d ia betic ket oaci d osis  
1 4 . A n y a c ute/c hr o nic s yste mic infecti o ns   
1 5. Rec urre nt ur o ge nital i nfecti o ns  
1 6. Patie nts at ris k f or v ol u me de pleti o n as  j u d ge d b y t he i n vesti gat or 
1 7. A n y c o n diti o n w hic h, i n t he j u d g me nt of t he I n vesti gat or, ma y re n d er t h e patie nt 
u na ble t o c o m plete t he st u d y  or w hic h ma y p ose a si g nifica nt ris k t o t he patie nt or patie nt 
s us pecte d or wit h c o nfir me d p o or pr ot oc ol or me dicati o n c o m plia nce 
 
3. 3   S u bject  e nr ol me nt a n d r a n d o miz ati o n  
T his is a si n gle ar m o pe n la bel st u d y. Eac h eli gi ble patie nt recr uite d i n st u d y will be  pr o vi de d 
wit h u ni q ue i de ntificati o n n u m ber.  
I n v esti gat or(s) s h o ul d kee p a rec or d, t he s u bject s cree ni n g l o g, of s ubject s w h o e ntere d pre-
st u d y scree ni n g. 
T he I n vesti gat or(s) will:  
1.  
O btai n si g ne d i nf or me d c o nse nt fr o m t he p ote ntial s u bject bef ore a n y st u d y s pecific 
pr oce d ures are perf or me d.  
2.  
Assi g n p ote ntial s u bject a u ni q ue e nr ol me nt n u m ber . 
3.  
Deter mi ne s u bject eli gi bilit y. See Secti o n 3. 1  a n d 3. 2 . 
If a s u bject wit h dr a ws fr o m partici pati o n i n t h e st u d y, t he n his/ her e nr ol me nt  c o de ca n n ot b e 
re use d. 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
1 7  (5 2 ) 
3. 4   Pr oce d ures f or h a n dli n g i nc orrectl y e n r olle d or r a n d o mize d s u bjects 
S u bject s w h o fail t o meet t he eli gi bilit y criteria s h o ul d n ot, u n der a n y circ u msta nces, be e nr olle d 
or recei v e st u d y me dicati o n.  T here ca n be n o e xce pti o ns t o t his r ule.  S u bject s w h o are e nr olle d, 
b ut s u bse q ue ntl y f o u n d n ot t o meet all t he eli gi bilit y criteria m ust n ot be i nitiate d o n treat me nt, 
a n d m ust be wit h dra w n fr o m t he st u d y.  
W here a s u bject d oes n ot meet all t he eli gi bilit y criteria b ut is i nc orrectl y starte d o n treat me nt, 
t he I n v esti gat or s h o ul d i nf or m t he Astra Ze n ec a st u d y p h ysicia n i m me diatel y, a n d a disc ussi o n 
s h o ul d occ ur b et wee n t he Astra Z e neca st u d y p h ysicia n a n d t he i n v esti gat or re g ar di n g w het h er 
t o c o nti n ue or disc o nti n ue t he s u bject fr o m treat me nt.  T he Astra Ze neca st u d y p h ysicia n m ust 
e ns ure all decisi o n s are a p pr o priatel y d oc u me nt e d.  
3. 5    Restricti o ns  
•  S u bjects m ust be i n a fasti n g state at least 8 h o urs pri or t o st u d y visit ( h o we ver, 
dri n ki n g water is all o we d). Per mitte d me dicati o ns ma y be ta ke n wit h w ater o nl y.  
 
•  S u bjects m ust ma ke e ver y atte m pt t o a d here t o t he dietar y a n d p h ysical acti vit y 
c ha n ges a n d g oals as disc usse d wit h t he I n vesti gat or(s).  
 
•  W o me n of c hil d -b eari n g p ote ntial m ust i m me diatel y c o ntact t he I n vesti gat or if t he y 
s us pect t he y mi g ht be pre g na nt a n d if t he y ha v e c h a n ge d, or pla n t o c h a n ge t hei r birt h 
c o ntr ol met h o d.  
 
•  If a s u bject arri ves f or a visit wit h o ut ha vi n g f oll o we d t he a b o v e i nstr ucti o ns, t he e ntire 
visit s h o ul d be resc he d ul e d ( wit hi n t he all o we d ti me -wi n d o w, if p ossi ble).  
 
 
3. 6   Disc o nti n u ati o n of i n vesti g ati o n al pr o d uct  
E ver y atte m pt wil l be ma de t o retai n s u bject o n st u d y me dicati o n. S u bjects w h o disc o nti n ue 
st u d y me dicati o n d uri n g t he treat me nt peri o d will be perf or me d t he E n d of treat me nt  visit 
( Visit no:  9 ) a n d will be c o ntacte d for  2  wee k s lat er a n d as k e d f or t h e pres e nce of a n y A E s. 
 
S u bjects are free t o disc o nti n ue i n vesti gati o nal pr o d uct at a n y ti me, wit h o ut prej u dice t o 
f urt her tr eat me nt a n d f oll o w u p. 
 
 
Ge ner al disc o nti n u ati o n criteri a:  
 
1. V ol u ntar y disc o nti n uati o n b y t he s u bject w h o is at a n y ti me free t o disc o nti n ue  his/ her 
pa rtici pati o n i n t he st u d y, wit h o ut prej u dice t o f urt her treat me nt 
2. Ris k t o s u bjects  as j u d ge d b y t he i n vesti gat or a n d/ or Astra Ze n eca  
3. Se vere n o n -c o m plia nce t o pr ot oc o l as j u d ge d b y t he i n vesti gat or a n d/ or Astra Ze neca 
4. I n c orrectl y e nr olle d s u bjects ( S ee Secti o n 5. 3 ) 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
1 8  (5 2 ) 
5 . A Es, ie, a n y cli nical A E, la b orat or y a b n or malit y or i nterc urre nt ill ness w hic h, i n t he o pi ni o n 
of t he i n vesti gat or, i n dicates t hat c o nti n ue d partici pati o n i n t he st u d y is n ot i n t he best i nterest  
of t he  s u bject  
6 . Maj or a n d/ or fre q ue nt h y p o gl yce mic e ve nts; If m ore t ha n o ne e v e nt of se vere  h y p o gl yc e mia, 
defi ne d as s y m pt o matic e ve nts re q uiri n g e xter n al assista nce d ue t o  se v ere i m pair me nt i n 
c o nsci o us ness or b e ha vi o ur, wit h a ca pillar y or plas ma  gl uc ose va l ue < 3 m m ol/ L ( < 5 4 m g/ d L), 
a n d pr o mpt rec o ver y aft er gl uc ose or  gl uca g o n a d mi nistrati o n occ urs, or if t he i n vesti gat ors 
deci des t hat c urre nt treat me nt  p oses t he s u bject at ris k of eit her re peate d h y p o gl yce mic e ve nts 
or se vere  h y p o gl yce mia.  
7. C o nsi der te m p orar y i nterr u pti n g da pa glifl ozi n if  D K A is s us p ecte d. T he patie nt s h o ul d be 
pr o m ptl y e val uate d. If D K A is c o nfir me d, i n vesti gati o nal pr o d uct(s) s h o ul d be disc o nti n ue d 
per ma ne ntl y.  
8. Ac ute re nal i ns uffi cie nc y or w ors e ne d c hr o ni c re n al i ns uffic ie nc y bas e d o n re p eat e G F R 
val ues (e G F R < 4 5 
m L/ mi n ute/ 1. 7 3 m 2). T he re -test s h o ul d be sc he d ul e d wit hi n 4 d a ys, 
w he ne ver p ossi ble .If a n u ne x pecte d, ac ute decli n e i n ki d ne y f u ncti o n is o bser ve d, t he patie nt 
s h o ul d be pr o m ptl y e val u ate d. V ol u me de pleti o n, h y p ote nsi o n, i nter -c urre nt me dical pr o ble ms 
a n d c o nc o mita nt dr u gs ma y ca use i n creases i n bl o o d creati ni ne. Uri nar y tract i nfecti o n a n d 
uri nar y o bstr ucti o n s h o ul d be c o nsi dere d. Se v eral dr u gs ma y ca use a decli ne i n ki d ne y f u ncti o n, 
es peciall y n o n -ster oi dal a nti-i nfla m mat or y dr u gs ( N S AI D) a n d certai n a nti bi otics s uc h as 
tri met h o pri m. If a n y dr u g is s us pecte d of ca usi n g or c o ntri b uti n g t o w orse ni n g ki d ne y f u ncti o n, 
t heir use s h o ul d be re-c o nsi dere d.  
9.  Pre g na nc y c o nfir me d b y a p ositi ve pre g n a nc y test or ot her wise v erifie d. A n 
A Z 
re pres e ntati ve s h o ul d be n otifie d if a patie nt bec o mes pre g na nt d uri n g t he c o urse of t he st u d y.  
 
 
Pr oce d ures f or disc o nti n u ati o n of a s u bject fr o m i n vesti g ati o n al pr o d uct 
 
A s u bject t hat disc o nti n ues 
treat me nt will al wa ys be as ke d a b o ut t he  reas o n(s) f or 
disc o nti n uati o n a n d  t he prese nce of a n y A Es. T h e Pri nci pal I n v esti gat or/s u b -i n vesti gat or will 
perf or m t he b est  p ossi ble o bser vati o n(s), test(s) a n d e val uati o n(s) as well as gi ve a p pr o priate 
me dicati o n a n d all  p ossi ble meas ures f or t he safet y  of t he s u bject. T he y will als o i m me diatel y 
i nf or m Astra Ze n eca of t h e wit h dra wal.  
  
If a s u bject is wit h dra w n fr o m st u d y, see Secti o n 3. 7  
3. 7   Criteri a f or wit h dr a w al fr o m st u d y 
3. 7. 1  Scree n f ail ures  
Scree ni n g fail ures are s u bjects w h o d o n ot f ulfil t he eli gi bilit y criteria f or t he st u d y, a n d 
t heref ore m ust n ot be i nitiate d o n st u d y treat me nt .  T hese s u bjects s h o ul d ha ve t he reas o n f or 
st u d y wit h dra wal rec or de d as ‘ Scree n fail ure’ (the p ote ntial s u bject w h o d o es n ot meet o ne or 
m or e criteri a re q uir e d f or partici pati o n i n a trial).   

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n +  Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
1 9  (5 2 ) 
3. 7. 2  Wit h dr a w al of t he i nf or me d c o n se nt 
S u bject s are free t o wit h dra w fr o m t he st u d y at a n y ti me (i n vesti gati o nal pr o d uct a n d  f urt her 
assess me nts), wit h o ut pr ej u dice t o f urt her treat me nt.  
A s u bject w h o wit h dra ws c o nse nt will al wa ys b e as ke d a b o ut t he reas o n(s) a n d t he pres e nce of 
a n y a d vers e e ve nts ( A E).  A Es will be f oll o we d u p ( See Secti o n 6. 4 ); s u bject diaries, gl uc o meter 
a n d st u d y dr u g s h o ul d be ret ur ne d b y t he s u bject.   
 
If a s u bject wit h dr a ws fr o m partic i pati o n i n t he st u d y, t he n his/ her e nr ol me nt  c o de ca n n ot b e 
re use d. Wit h dra w n s u bjects will n ot be re place d.  
3. 8    Disc o nti n u ati o n of t he st u d y  
T he st u d y ma y be st o p pe d if, i n t he j u d g me nt of Astra Ze neca, trial s u bjects are place d at u n d ue 
ris k beca use of cli nicall y si g nifica nt fi n di n gs t hat meet i n di vi d ual st o p pi n g criteria or are 
ot her wi se c o nsi dere d si g nifica nt  
Re gar dless of t he reas o n f or ter mi nati o n, all d ata a v aila ble f or t he s u bject at t he ti me of 
disc o nti n uati o n of f oll o w -u p m ust be rec or de d i n t he C R F. All reas o ns f or disc o nti n uati o n of 
treat me nt m ust be d oc u m e nte d. 
I n ter mi nati n g t he st u d y, t he S p o ns or will e ns ure t hat a de q uate c o nsi derati o n is gi ve n t o t he 
pr otecti o n of t he s u bjects’ i nterests. 
4  S T U D Y P L A N A N D TI MI N G O F P R O C E D U R E S  
T his is a 2 4 -wee k  o pe n la bel pr os pecti ve  st u d y. After eli gi bilit y c hec k as per criteria me nti o ne d 
i n secti o n 3. 1 a n d 3. 2 patie nts, will be recr uite d i n t he st ud y a n d pr oce d ures as me nti o ne d i n 
bel o w ta ble will be perf or me d at vari o us sc h e d ule d visits.  
Ta ble 1  
Assess m e nts  
Visit 1  
Visit 2  
Visit 3 # 
Visit 4 # 
Visit 5  
Visit 6 # 
Visit 7  
Visit 8 #  
Visit 9 
( E O T) 
V isit 1 0 
( E o S) 
E nr ol me nt *  
(-1 w k)  
( 0 W k) 
( 1 W k) 
( 4 w k) 
( 8 w k) 
( 1 2 w k) 
( 1 6 w k) 
( 2 0 w k)  
( 2 4 w k)  
( 2 6 w k)  
Wi n d o w peri o d  
( D a ys) 
( ± 5) 
( ± 5) 
( ± 2) 
( ± 2) 
( ± 5) 
( ± 2) 
( ± 5) 
( ± 2) 
(+ 5)  
(+ 2)  
I nf or me d 
C o nse nt  
X  
  
  
  
  
  
  
  
  
 
P h ysical 
E xa m  
X  
X  
  
  
X  
  
X  
  
X  
X  

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
2 0  (5 2 ) 
Vita l Si g ns 
X  
X  
  
  
X  
  
X  
  
X  
X  
Eli gi bilit y 
c hec k  
X  
X  
  
  
  
  
  
  
  
  
H b A 1c  
X  
X  
  
  
X  
  
X  
  
X  
X  
Fasti n g 
Plas ma 
Gl uc ose 
( F P G) * * 
  
X  
  
  
X  
  
X  
  
X  
X  
Wei g ht & 
Hei g ht  
  
X  
  
  
X  
  
X  
  
X  
X  
Waist 
circ u mfere nce  
  
X  
  
  
X  
  
X  
  
X  
X  
B MI ( B o d y 
Mass I n d e x)  
  
X  
  
  
X  
  
X  
  
X  
X  
Bl o o d 
Press ure  
  
X  
  
  
X  
  
X  
  
X  
X  
Safet y la bs  
X  
X  
  
  
X  
  
X  
  
X  
X  
E C G  
  
X  
  
  
  
  
X  
  
X  
X  
A E 
assess me nt  
  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Uri nal ysis  
X  
X  
  
  
X  
  
X  
  
X  
X  
U P T 
( W O C B P) 
X  
X  
  
  
X  
  
X  
  
X  
X  
I P 
dis pe nsati o n  
  
X  
  
  
X  
  
  
  
  
  
I P 
acc o u nta bi lit y 
  
X  
X  
X  
X  
X  
X  
  
X  
X  
*e nr ol me nt a n d Visit 2  ca n c oi nci de t o e nt er patie nt i nt o t he st u d y, # tele p h o nic visit 
* *  S u bjects m ust be i n a fasti n g state at least 8 h o urs pri or t o st u d y visit.  

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
2 1  (5 2 ) 
 
4. 1   Scree ni n g/ E nr ol me nt  peri o d  
Pr oce d ures will be perf or me d acc or d i n g t o t he St u dy Pl a n.  
El i gi ble patie nts will be e nr olle d i nt o t he st u d y a n d u ni q ue i de ntificati o n n u m ber will be 
pr o vi de d t o eac h p atie nt.  
4. 2   Tre at me nt peri o d  
Descri pti o ns of t he pr oce d ures f or t his peri o d  are i ncl u de d i n t he St u dy Pl a n.  
4. 3   F oll o w -u p peri o d  
Descri pti o ns of t he pr oce d ures f or t his peri o d  are i ncl u de d i n t he St u dy Pl a n.  
5  S T U D Y A S S E S S M E N T S  
Electr o nic  Case Re p ort F or ms ( e C R F) will be use d f or data c ollecti o n a n d q uer y ha n dli n g.  
T he i n vesti gat or will e ns ure t hat data are rec or de d o n t he e C R F as s pecifie d i n t he Cli ni cal 
St u d y P r ot oc ol a n d i n acc or da nce wit h t he i nstr ucti o ns pr o vi de d. 
T he i n vesti gat or e ns ur es  t he acc urac y, c o m plete ness, eC R Fs i ncl u de:  ti meli ness of t he data 
rec or de d a n d of t h e pr o visi o n of a ns wers t o dat a q ueries acc or di n g t o t he Cli nical St u d y 
A gree me nt. T h e i n vesti gat or will si g n t he c o m plete d electr o ni c Case Re p ort F or ms.  A c o p y 
of t he c o m plete d el ectr o nic  Case Re p ort F or ms will be arc hi ve d at t he st u d y site.  
5. 1  Effic ac y assess me nts  
5. 1. 1  Gl yc os yl ate d H ae m o gl o bi n -H b A 1c  
H b A 1c is a w ell -esta blis he d  meas ur e of  gl yce mic efficac y a n d c o nsi dere d t o be a n  acce pta ble 
sec o n dar y e n d p oi nt t he assess me nt f or t he deter mi nati o n of gl yce mic efficac y.  H b A 1c will be 
a nal yse d b y a ce ntr al  la b orat or y acc or di n g t o t he pr oce d ures descri be d i n t he La b orat or y  
Ma n ual w hic h will be distri b ute d t o eac h st u d y site d uri n g site i nitiati o n.  
. 
5. 1. 2  F asti n g Pl as m a Gl uc ose ( F P G ) 
F P G is a well -est a blis he d  meas ure of gl y ce mic effi cac y a n d c o nsi dere d t o b e a n 
acce pta ble sec o n dar y e n d p oi nt. 
 
5. 1. 3  Wei g ht a n d hei g ht  
T he s u bject’s w ei g h t will be rec or de d i n kil o gra m ( k g) t o o ne deci mal place, o n a 
fasti n g st o mac h wit h li g ht cl ot hi n g a n d n o s h oes. T he s u bject’s hei g ht will be 
rec or de d i n ce nti metres, wit h n o s h oes. All rea di n gs s h o ul d be rec or de d as acc uratel y 
as p ossi ble a n d t he sa me sca le s h o ul d be use d f or all assess me nts f or a gi ve n s u bject. 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
2 2  (5 2 ) 
5. 2    S afet y assess me nts  
T he Pri nci pal I n vesti gat or is res p o nsi ble f or e ns uri n g t hat all staff i n v ol ve d i n t he st u d y is  
fa miliar wit h t he c o nte nt of t his secti o n. 
 
5. 2. 1  L a b or at or y s afet y ass ess m e nts  
Bl o o d sa m ples s hall be c ollecte d a n d pr o cesse d as per t he l ocal affiliate d la b orat or y criteria.  
 
Deteri or ati o n as c o m pare d t o baseli ne i n pr ot oc ol -ma n date d la b orat or y val u es, vital si g ns a n d  
ot her safet y v aria bles will o nl y be re p orte d as A Es if t he y are cli nica ll y si g nifica nt, f ulfil a n y 
of t he S A E criteri a or are t he reas o n f or disc o nti n uati o n of treat me nt wit h t he i n vesti gati o nal  
pr o d uct, or re q uire t he s u bject t o recei ve s p ecific c orrecti ve t h era p y. If a d eteri orati o n i n a  
la b orat or y val u e/ vital si g n is ass ociate d wit h cli nical si g ns a n d s y m pt o ms, t he si g n/s y m pt o m 
will be re p orte d as a n A E a n d t he ass ociat e d la b orat or y res ult/ vital si g n will be c o nsi dere d as  
a d diti o nal i nf ormati o n. A n y ne w or a g gra vat e d cli nicall y rele va nt a b n or mal me dical fi n di n g  
at a p h ysical e x a mi nati o n or E C G e val uati o n as c o m pare d wit h t he bas eli ne assess me nt will 
be re p ort e d as a n A E.  
 
Cli nicall y rele va nt deteri orati o n i n n o n -pr ot oc ol -ma n date d meas ure me nts will be re p orte d as  
A E(s).  
 
W here v er p ossi ble t he re p orti n g i n vesti gat or uses t he c li nical, rat her t ha n t he la b orat or y t er m 
(e g, a nae mia vers us l o w hae m o gl o bi n val ue). 
T he f oll o wi n g la b orat or y varia bles  will be meas ure d:  
T a ble 2  
L a b or at or y S afet y V ari a bles  
H ae m at ol o g y/ H ae m ost asis ( w h ole bl o o d)  
Cli nic al C he mistr y (ser u m or pl as m a)  
B - He mat ocrit  
 
S/ P -Creati ni ne  
B -Le u k oc yte c o u nt  
S/ P -Bilir u bi n, t otal  
B -Le u k oc yte differe ntial c o u nt (a bs ol ute c o u nt)  
S/ P -Al kali ne p h os p hatise ( A L P)  
B -Platelet c o u nt  
S/ P -As partate tra nsa mi nase ( A S T)  
B - Hae m o gl o bi n ( H b)  
S/ P -Ala ni ne tra nsa mi nase ( A L T)  
Uri n al ysis  ( di pstic k) 
S/ P -Al b u mi n  
U -H b/ Er yt hr oc ytes/ Bl o o d  
S/ P -P otassi u m  
U -Pr otei n/ Al b u mi n  
S/ P -Calci u m, t otal  
U -Gl uc ose  
S/ P -S o di u m  
 
S/ P -Creati ne ki nase ( C K)  
 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
2 3  (5 2 ) 
T he I nvesti g at or s h o ul d m ake a n assess me nt of t he av ail a ble res ults wit h re g ar d t o cli nic ally 
relev a nt a b n or m alities.  T he l a b or at ory res ults s h o ul d be si g ne d a n d d ate d a n d ret ai ne d at 
ce ntre as s o urce d at a f or l a b or at ory v ari a bles.  F or i nf or m ati o n o n h o w  A Es b ase d o n 
l a b or at ory tests s h o ul d be rec or de d a n d r e p orte d, see Secti o n 6. 3  
N B.  I n case a s u bject s h o ws a n A S T or  A L T ≥3 x U L N or  t otal bilir u bi n ≥2 x U L N please refer 
t o A p pe n di x B  ‘ Acti o ns r e q uire d i n cas es of c o m bi ne d i ncrease of A mi n otr a nsferas e a n d T otal 
Bilir u bi n –  H y’s La w’, f or f urt her i nstr u cti o ns.  
5. 2. 2  P h ysic al e x a mi n ati o n  
A brief p h ysical e xa mi nati o n s h o ul d i ncl u de t he car di o vas c ular s yste m, l u n gs,   
a b d o me n, a n d e xtr e mities, a n d a n y or ga n s yste m perti ne nt t o t he s u bject’s si g ns,  
s y m pt o ms, or A Es. T he s u bject s h o ul d al wa ys be e val uate d f or t he prese nce of oe de m a.  
 
5. 2. 3  E C G  
Resti n g 1 2 -le a d E C G 
A 1 2 -lea d E C G will be ta ke n after t he s u bject has bee n l yi n g d o w n resti n g. T he E C G will 
be  e val uat e d b y t he i n vesti gat or a n d e ntere d as ‘ N or mal’ or ‘ A b n or mal’ i n t he e C R F. If t he 
E C G  is e val uate d as “ A b n or mal” t he i n vesti gat or s h o ul d d oc u me nt t he s pecific 
a b n or malit y.  
 
5. 2. 4  Vit al si g ns  
Vital si g ns will be meas ure d a n d rec or de d d uri n g eac h o n site visit t hr o u g h t he st u d y 
d urati o n.  
5. 2. 4. 1  
P ulse a n d bl o o d press ure  
P ulse a n d B P rea di n gs s h o ul d be ta ke n w hile t he s u bject is i n  a c o mf orta b le seate d p ositi o n 
wit h t he ar m s u p p orte d at t he le v el of t he h eart. All rea di n gs  s h o ul d be rec or de d. A sta n dar d 
merc ur y s p h y g m o ma n o meter wit h  a sta n d ar dise d c uff a d a pte d t o t he siz e of t he s u bject’s 
ar m is rec o m me n d e d.  
 
5. 3   Ot her assess me nts  
Self -m o nit ore d  bl o o d gl uc ose rea di n gs a n d h y p o gl yce mic  e v e nts will be c ollecte d i n a  
s u bject diar y a n d re vie we d b y t he i n vesti gat or at eac h visit. 
5. 3. 1    H y p o gl yce mic e ve nts  
S u bject self -m o nit ori n g of F B G  is perf or me d i n or der t o re d u ce t he ris ks ass ociate d wit h 
pr ol o n ge d h y per gl yce mia a n d t o c o nfir m s y m pt o ms of h y p o gl yce mia. S u bjects will be as ke d  t o 
perf or m s elf -m o nit ori n g of F B G  usi n g gl uc o meters pr o vi de d b y Astra Z e neca. T he s u bjects  will 
recei v e i nstr ucti o ns f or t he use of t he gl uc o m eter acc or di n g t o t he ma n ufact urer’s i nstr ucti o ns. 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
2 4  (5 2 ) 
F B G  s h o ul d be self-m o nit ore d  o nce e v er y wee k  b et wee n Visit 2 a n d 1 0  T he res ults s h o ul d be 
rec or de d i n t he s u bject diar y, w hic h will be c ollecte d a n d re vi e we d b y t he st u d y pers o n nel at 
eac h visit starti n g wit h Visit 3; rec or d will be st ore d i n t he i n vesti gat or st u d y file.  
T he me m or y o f t he gl uc o meter s h o ul d be re vie we d a n d c o m pare d wit h t he rea di n gs i n t he 
s u bject’s diar y. T he gl uc ose val ues s h o ul d be re vie we d b y t he st u d y pers o n nel t o i de ntif y a n y  
u n us uall y hi g h or l o w v al ues, a n d t o c o nfir m t h a t s elf-m o nit ori n g was p erf or me d b y t he  su bject. 
If fi n g erstic k gl uc os e v al ues are dis c or da nt wit h ce ntr al la b orat or y res ults or wit h cli nical 
s y m pt o ms, t he s u bject’s gl uc o meter s h o ul d be t este d a n d t he gl u c o meter i nstr ucti o ns  s h o ul d be 
re-re vie we d wit h t he s u bject. 
If self-m o nit ore d F B G  is a b o ve 2 4 0 m g/ d L t he n s u bject s h o ul d re p eat t he F B G  o n t he sa me da y. 
If t he sec o n d F B G  val ue is a b o ve 2 4 0 m g/ d L, t he s u bject s h o ul d c o ntact t he st u d y ce ntre a n d be 
sc he d ule d f or a ce ntral la b orat or y F B G  m eas ure me nt wit hi n o ne wee k.  
 
If ce ntral la b orat or y val u es s h o w si milar val ues, t he s u bject s h o ul d be disc o nti n ue d (if t here is 
n o o b vi o us  e x pla nati o n, i.e. i nfecti o ns)  a n d treat e d acc or di n g t o l ocal practice . 
A se parate secti o n i n t he e C R F 
will be use d t o d oc u me nt all re p or te d e pis o des of 
h y p o gl ycae mia. T he s u bjects will be as ke d t o c hec k t heir bl o o d gl uc ose  if t he y de vel o p 
s y m pt o ms s u g gesti ve of h y p o gl yce mia a n d t o rec or d s pecific s y m pt o ms i n t he  s u bject diar y. 
T he I n v esti gat or is res p o nsi ble f or q u esti o ni n g t he s u bject a b o ut all s y m pt o ms  re p orte d i n t he 
diar y a n d f or deter mi ni n g if t he y meet t he cli nical defi niti o n of h y p o gl yce mia.  O nl y s y m pt o ms 
a n d/ or bl o o d gl uc ose val ues t hat meet t he defi niti o n of h y p o gl yca mia s h o ul d  be re p orte d o n t he 
h y p o gl yce mia e C R F pa g es.  
 
A h y p o gl y ce mic e v e nt ca n be eit her:  
•  
S y m pt o ms of h y p o gl yce mia wit h a l o w bl o o d gl uc ose rea di n g ( < 6 3 m g/ d L)  
•  
A l o w bl o o d gl uc ose rea di n g ( < 6 3 m g/ d L [ < 3. 5 m m ol/ L])  
•  
S y m pt o ms of h y p o gl yce mia wit h o ut a bl o o d gl uc ose rea di n g  
 
H y p o gl yce mic e pis o des or disc o nti n uati o n  d ue t o  h y p o gl yce mia s h o ul d n ot be re p ort e d o n t he  
A E e C R F pa ge u nl ess t he e ve nt f ulfils pr ot oc ol crit eria f or a S A E (see Secti o n 6. 4 ). I n t his case, 
a n S A E m ust be re p orte d i n a d diti o n t o t he h y p o gl yce mia e C R F p a ges f or h y p o gl yce mia . 
 
S y m pt o ms s u g gesti ve of h y p o gl yce mia wit h a n ass ociate d ca pillar y or plas ma gl uc ose val ue  
≥6 3 m g/ d L ( ≥3. 5 m m ol/ L), s h o ul d be rec or de d as a n A E rat h er t ha n as a h y p o gl yce mic e ve nt.  
If t he p h ysicia n d oes n ot c o nsi der t he gl uc ose m eas ure me nt t o be acc urate, h o we ver, t he e ve nt 
s h oul d be d oc u me nte d as a h y p o gl yce mic e v e nt i n t he h y p o gl yce mia e C R F.  
 
F or t he e val uati o n of h y p o gl yce mic e ve nts, t his st u d y will use t he defi niti o ns pr o vi de d i n t he  
C o m mittee f or pr o priter y me dici nal pr o d uct (C P M P ) g ui da nce o n cli nical i n vesti gati o n of 
me dici nal pr o d ucts i n t he treat me nt of dia betes  
mellit us, as descri be d be l o w. 
•  
Maj or h y p o gl yce mic e ve nts, defi ne d as s y m pt o matic e ve nts re q uiri n g e xter nal  assista nce d ue t o 
se vere i m pair me nt i n c o nsci o us ness or be ha vi our, wit h a ca pillar y  or plas ma gl uc ose val ue < 5 4 
m g/ d L ( < 3. 0 
m m ol/ L)  if a vaila ble, a n d pr o m pt rec o ver y after gl u c ose or gl uca g o n 
a d mi nistrati o n. 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
2 5  (5 2 ) 
•  
Mi n or h y p o gl yce mic e ve nt, defi ne d as eit her a s y m pt o matic e pis o de wit h a  ca pillar y or plas ma 
gl uc ose meas ure me n t < 6 3 m g/ d L ( < 3. 5 m m ol/ L) re gar dless of nee d f or e xter nal assista nce or a n 
as y m pt o matic ca pillar y or plas ma gl uc ose  meas ure me nt bel o w 6 3 m g/ d L ( 3. 5 m m ol/ L), t hat 
d oes n ot q ualif y as a maj or e pis o de  
•  
E ve nts s u g gesti ve of h y p o gl yce mia, defi ne d as a s y m pt o mati c e ve nt wit h o ut a c o nfir mat or y 
bl o o d gl uc ose meas ure me nt.  
 
Data t o be c ollecte d f or eac h h y p o gl yce mic e ve nt:  
•  
Dat e a n d ti me of e pis o de (start a n d st o p)  
•  
W het her t he s u bject was slee pi n g at t he ti me of t he e ve nt  
•  
W het her s y m pt o ms were prese nt, a n d list of s y m pt o ms 
•  
P ossi ble c o ntri b uti n g fact ors  
•  
W het her a fi n gerstic k val ue was o btai ne d, a n d if s o, t he plas ma gl uc ose val ue  
•  
W het her i nter ve nti o n was nee de d f or rec o ver y  
•  
H o w t he e pis o de was treate d  
•  
W het her rec o ver y was pr o m pt after treat me nt  
•  
Ti me of last a nti -dia b etic a ge nts a d mi nistrati o n  
•  
Ti me of last meal a n d its c o nte nts  
 
T he s u bject diar y will be re vie we d a n d t he h y p o gl yce m ic e ve nt dat a will be tra nscri be d i nt o t he 
e C R Fs at eac h cli nical visit. A ne w diar y f or t he ne xt peri o d will be ha n de d o ver t o t he  s u bject 
if nee de d. If a maj or h y p o gl yce mic e ve nt or m ore t ha n o ne mi n or e ve nt has occ urre d si nce t he 
pre vi o us visit, t he s u b ject s h o ul d c o ntact t he i n vesti gat or. 
 
5. 3. 2  Uri n ar y a n d Ge nit al I nfecti o ns  
T he f oll o wi n g is prese nt e d t o assist i n t he classificati o n a n d ma na ge m e nt of i nfecti o ns of t he  
uri nar y a n d g e nital tracts i n st u dies wit h da pa glifl ozi n. It is n ot i nte n de d t o s u p pla nt  
i nvesti gat ors’ cli nical j u d ge me nt.  
 
Uri n ar y Tr act I nfecti o ns  
If bas e d o n t he s u g g esti ve si g ns or s y m pt o ms ( d ys uria, ur ge nc y or fre q ue nc y of uri n ati o n, 
s u pra p u bic or p eri neal disc o mf ort, fla n k, bac k, or a b d o mi nal pai n, c ost o verte bral a n gl e  
te n der ness, na us ea, v o miti n g, fe ver, c hills, or se psis) t he i n vesti gat or belie ves t hat a uri nar y  
tract i nf ecti o n ma y b e prese nt, uri n e c ult ures (i n a l ocal la b orat or y) s h o ul d be o btai ne d t o 
c o nfir m a pres u m pti ve dia g n osis of c ystitis, uri nar y tract i nfecti o n, p yel o ne p hritis,  or  pr ostatitis. 
Mi d -strea m cl ea n catc h uri ne c ollecti o ns are rec o m me n de d. Cli nical j u d ge me nt  a n d l ocal 
sta n dar ds of care s h oul d a p pl y t o decisi o ns c o ncer ni n g t hera p y.  A n y treat me nt nee ds t o be 
d oc u me nte d i n t he e C R F.  
 
Bet wee n s c he d ule d visits, s u bjects ma y e x perie nce n o vel si g ns or s y m pt o ms t hat are  p ote ntiall y 
i n dicati ve of uri nar y or a ge nital tract i nf ecti o n. T he s u bject s h oul d c o ntact t he  i n vesti gat or b y 
tele p h o ne. A n u nsc he d ul e d visit will be pla n ne d as s o o n as p ossi ble, prefera bl y wit hi n 2 4 h. T he 
i nvesti gat or will ta ke t he s u bject’s rece nt hist or y, a mi dstrea m  uri ne sa m ple will be o btai ne d f or 
uri ne a nal yses a n d a ma n date d uri ne c ult ure, a n d it is als o  rec o m me n de d t hat a ge nital s wa b is 
d o ne, if i n dicate d. A nal yses a n d c ult ure(s) are t o be  perf or me d at t he l ocal la b orat or y. T he 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
2 6  (5 2 ) 
i n vesti gat or will f oll o w l ocal g ui deli nes t o rec o m me n d treat me nt f or uri nar y tract i nf ecti o n or 
ge nital tract i nfecti o n.  
 
I n v esti gati o nal pr o d uct s h o ul d be te m p orar y st o p pe d i n s u bjects wit h cli nical e vi de nce of u p per 
uri nar y t ract i nf ecti o n (e g, p yel o ne p hritis) or pres u me d ur ose psis u ntil t he c o urse of tr eat me nt 
of t he i nfecti o n has bee n c o m plete d a n d cli nical rec o ver y has occ urre d. It is  rec o m me n d e d t hat 
a f oll o w-u p uri ne c ult ure is o btai ne d wit hi n 7 da ys of cli nical rec o ver y  fr o m a d oc u me nte d U TI. 
W het her a d diti o nal t hera p y is prescri be d beca us e of c ult ure res ults  s h o ul d be deter mi ne d b y 
I n v esti gator j u d ge me nt.  
 
Ge nit al Tr act I nfecti o ns  
 
T he dia g n osis of va gi nitis, v ul v o va gi nitis, v ul vitis or bala nitis ca n be m a de base d o n p h y sical 
e xa mi nati o ns, c ult ure of secreti o ns or a t hera pe utic res p o nse t o treat me nt of f u n gal or ot her  
va gi nal pat h o ge ns. A uri ne c ult ure is n ot re q uire d f or dia g n osis of ge nital i nfecti o ns if t he  
dia g n osis is c o nfir me d b y p h ysical e xa mi nati o n, c ult ure of sec reti o ns, or a t hera pe utic res p o nse 
t o treat me nt of f u n gal or ot her va gi nal pat h o g e ns. A n y treat me nt nee ds t o  b e d oc u me nte d i n t he 
e C R F. 
 
 
5. 3. 3  V ol u me De pleti o n  
Patie nts at ris k of v ol u me de pleti o n d ue t o c o -e xisti n g c o n diti o ns or c o nc o mita nt me dicati o ns 
s h o ul d ha ve caref ul m o nit ori n g of t heir v ol u me stat us as j u d ge d b y t he I n vesti gat or.  E ve nts of 
v ol u me de pleti o n i nc l u de de h y drati o n, h y p o v ole mia, or h y p ote nsi o n. 
 
 
5. 3. 4  Di a betic ket o aci d osis  
Patie nts treate d wit h st u d y me dicati o n w h o pres e nt wit h si g ns a n d s y m pt o ms c o nsiste nt wit h  
ket oaci d osis, i ncl u di n g na usea, v o miti n g, a b d o mi nal pai n, malaise a n d s h ort ness of breat h, 
s h oul d be assesse d f or ket oaci d osis, e ve n if bl o o d gl uc ose le vels are < 1 4 m m ol/l ( 2 5 0 m g/ dl). 
If ket oa ci d osis is s us pecte d, disc o nti n uati o n or te m p orar y i nterr u pti o n of st u d y dr u g s h o ul d be 
c o nsi dere d a n d t he patie nt s h o ul d be pr o m ptl y e val uate d.  
 
 
 
 
 
 
5. 3. 5 Re n al E ve nts  
Re nal e ve nts are defi ne d b y d o u bli n g of ser u m creati ni ne, dial ysis a n d re nal 
tra ns pla ntati o n 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
2 7  (5 2 ) 
5. 3. 6  H os pit aliz ati o n f or He art F ail ure  
Patie n ts w h o prese nt wit h s y m pt o ms of heart fail ure a n d get h os pitalize d f or m ore t ha n 2 4 
h o urs nee d t o e v al ua te d f urt her t o u n dersta n d t h e reas o n f or n e w or w orse ni n g of heart fail ure 
s y m pt o ms.  
H F is defi ne d as a n e ve nt t hat meets all of t he f oll o wi n g criteria : 
–  A d mitte d t o t he h os pital wit h a pri mar y dia g n osis of H F  
–  Le n gt h -of -sta y i n h os pital e xte n ds f or at least 2 4 h o urs 
–  E x hi bits d oc u me nte d ne w or w orse ni n g s y m pt o ms d ue t o H F o n prese ntati o n, 
i ncl u di n g at least o ne of t he f oll o wi n g: 
• 
D ys p nea ( d ys p nea wit h e xert i o n, d ys p nea at r est, ort h o p nea, 
par o x ys mal n oct ur nal d ys p nea); decrease d e x ercis e t olera nce; fati g ue; 
o t her s y m pt o ms of w orse ne d e n d-or ga n perf usi o n or v ol u me o verl oa d  
–  P hysic al ex a mi n ati o n fi n di n g  c o nsi d er e d t o b e d u e t o H F, i ncl u di n g n e w or 
w ors e n e d:  
•  
P er i p h er al e d e m a 
•  
I ncr e asi n g a b d o mi n al dist e nsi o n or ascit es (i n a bs e nc e of pri m ar y h e p atic 
dis e as e)  
•  
P ul m o n a r y r al es/cr ackl es/cr e pit ati o ns 
•  
I ncr e as e d j u g ul ar v e n o us pr ess ur e a n d/ or h e p at oj u g ul ar r efl ux 
•  
S 3 g all o p  
•  
Cli nic all y si g nific a nt or r a pi d w ei g ht g ai n t h o u g ht t o b e r el at e d t o fl ui d 
r et e nti o n 
–  L a b or at ory evi d e nc e of n e w or w ors e ni n g H F, if o bt ai n e d wit hi n 2 4 h o urs of 
pr es e nt ati o n, i ncl u di n g:  
•  
I ncr e as e d B N P/ N-t er mi n al pr o-B N P ( N T -pr o B N P) c o nc e ntr ati o ns c o nsist e nt 
wit h d ec o m p e ns ati o n of HF (s uc h as B N P > 5 0 0 p g/ m L or N T-pr o B N P > 2, 0 0 0 
p g/ mL),  
•  
R a di ol o gic al evi d e nc e of p ul m o n ary c o n g esti o n  
•  
N o n -i nv asi v e or i nv asi v e di a g n ostic e vi d e nc e of cli nic ally si g nific a nt el e v at e d 
l eft- or ri g ht -si d e d v e ntric ul ar filli n g pr ess ur e or l o w c ar di ac o ut p ut. 
O R  
•  
I nv asi v e di a g n ostic evid e nc e wit h ri g ht h e art c at h eriz ati o n s h o wi n g a 
p ul m o n ary c a pill ary w e d g e pr ess ur e ( p ul m o n ar y art ery oc cl usi o n pr ess ur e) 
≥1 8 m m H g, c e ntr al v e n o us pr ess ur e ≥ 1 2 m m H g, or a c ar di ac i n d ex < 2. 2 
L/ mi n/ m 2 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
2 8  (5 2 ) 
–  Recei ves i nitiati o n or i nte nsificati o n of treat me nt s pecificall y f or H F, i n cl u di n g 
at least 1 of t he f oll o wi n g:  
▪ 
A u g m e nt ati o n i n or al di ur etic t h er a py  
▪ 
I ntr a v en o us di ur etic, i n otr o p e, or v as o dil at or t h er a py  
▪ 
M ec h a nic al or s ur gic al i nt er v e nti o n, i ncl u di n g:  
•  
M ec h a nic al circ ul at or y s u p p ort ( e. g., i ntr a -a ortic b all o o n p u m p, 
v e ntric ul ar assist d e vic e)  
•  
M ec h a nic al fl ui d r e m ov al ( e. g., ultr afiltr ati o n, h e m ofiltr ati o n, 
di a l ysis) 
 
6  S A F E T Y R E P O R TI N G A N D  M E DI C A L M A N A G E M E N T  
T he Pri nci pal I n vesti gat or is res p o nsi ble f or e ns uri n g t hat all staff i n v ol ve d i n t he st u d y are  
fa miliar wit h t he c o nte nt of t his secti o n. 
6. 1   Defi niti o n of a d verse e ve nts  
A n a d vers e e ve nt is t he d e vel o p me nt of  a n y u nt o w ar d me dical o cc urre nce i n a s u bject or cli nical 
st u d y s u bject a d mi nistere d a me dici n al pr o d uct a n d w hic h d oes n ot necessaril y ha ve a ca us al 
relati o ns hi p wit h t his treat me nt.   A n A E ca n t h eref ore be a n y u nfa vo ura ble a n d u ni nte n de d si g n 
(e. g. a n ab n or mal la b orat or y fi n di n g), s y m pt o m (f or e xa m ple na us ea, c h est pai n), or disease 
te m p orall y ass ociate d wit h t he use of a me dici nal pr o d uct, w het her or n ot c o nsi dere d relat e d t o 
t he me dici nal pr o d uct.  
T he ter m A E is u se d t o i n cl u de b ot h seri o us a n d n o n-seri o us A Es a n d ca n i n cl u de a det eri orati o n 
of a pre -e xisti n g me dical occ urre nce. A n A E ma y o cc ur at a n y ti me, i ncl u di n g r u n -i n or was h o ut 
peri o ds, e ve n if n o st u d y treat me nt has bee n a d mi nistere d.  
6. 2   Defi niti o ns of seri o us a d verse e ve nt  
A seri o us a d v erse e ve nt is a n A E o cc urri n g d uri n g a n y st u d y p hase (i.e., r u n -i n, treat me nt, 
was h o ut, f oll o w -u p), t hat f ulfils o ne or m ore of t h e f oll o wi n g criteria:  
•  
Res ults i n deat h  
•  
Is i m me diatel y life-t hreate ni n g 
•  
Re q uires i n -s u bject h os pi talisati o n or pr ol o n gati o n of e xisti n g 
h os pitalisati o n  
•  
Res ults i n persiste nt or si g nifica nt disa bilit y  or i nca pacit y.  
•  
Is a c o n ge nital a b n or malit y or birt h defect 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
2 9  (5 2 ) 
•  
Is a n i m p orta nt me dical e ve nt t hat ma y je o par dize t he s u bject or ma y 
re q uire me di cal i nter venti o n t o pre ve nt o ne of t he o utc o mes l iste d a b o ve. 
F or f urt her g ui da n ce o n t he defi niti o n of a S A E, s ee A p pe n di x A  t o t he Cli nical St u d y Pr ot oc ol. 
 
6. 3   Rec or di n g of a d verse e ve nts  
6. 3. 1  Ti m e peri o d f or c ollecti o n of a d verse e ve nts  
A d verse  E ve nts will be c ollecte d t hr o u g h o ut t he treat me nt peri o d a n d i ncl u di n g t he f oll o w -u p 
peri o d of o n e wee k after e n d of st u d y . S A Es will be rec or de d fr o m  t he ti me of i nf or me d c o nse nt. 
6. 3. 2  F oll o w -u p of u nres ol ve d a d verse e ve nts  
A n y A Es t hat are u nres ol ve d at E O S visit  are f oll o we d u p b y t he I n v esti gat or f or 
as l o n g as 
me dical l y i n dicate d, b ut wit h o ut f urt her rec or di n g i n t he C R F. 
Astra Ze neca retai ns t h e ri g ht t o re q uest a d diti o nal i nf or mati o n f or a n y s u bject wit h 
o n g oi n g A E(s)/ S A E(s) at t he e n d of t he st u d y, if j u d ge d necessar y.  
6. 3. 3  V ari a bles  
T he f oll o wi n g varia bles will be c olle ct f or eac h A E;  
•  
A E ( ver bati m)  
•  
T he date  w h e n t he A E st arte d a n d st o p pe d  
•  
Select t he a p pr o priate as re q uire d: ma xi m u m i nte nsit y or i nt e nsit y or 
c ha n ges i n i nte nsit y  
•  
W het her t he A E is seri o us or n ot  
•  
I n v esti gat or ca us alit y rati n g a gai nst t he I n vesti gati o nal Pr od uct ( yes or 
n o)  
•  
Acti o n ta ke n wit h re g ar d t o i n vesti gati o nal pr o d uct  
•  
A E ca use d  s u bj ect’s wit h dra wal fr o m st u d y (yes or n o ) 
•  
O utc o me.  
I n a d diti o n, t he f oll o wi n g varia bles will be c ollecte d f or S A Es:  
•  
Date A E met criteria f or seri o us A E  
•  
Date I n vesti gat or b eca m e a ware of seri o us A E  

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
3 0  (5 2 ) 
•  
A E is seri o us d ue t o  
•  
Date of h os pitalisati o n  
•  
Date of disc h ar ge  
•  
Pr o ba ble ca us e of deat h  
•  
Date of deat h  
•  
A ut o ps y perf or me d  
•  
Ca usalit y assess me nt i n relati o n t o St u d y pr oce d ur e(s)  
•  
Ca usalit y  assess me nt t o ot her me dicati o n  
•  
Descri pti o n of A E.  
It is i m p orta nt t o disti n g uis h bet wee n s eri o us a n d s e vere A Es.  Se v erit y is a meas ure of i nte nsit y 
w hereas seri o us ness is d efi ne d b y t he criteri a i n Secti o n 6. 2 .  A n A E of s e vere i nte nsit y nee d 
n ot necessaril y b e c o nsi d ere d seri o us.  F or e x a m ple, na usea t hat persists f or se veral h o urs ma y 
be c o nsi dere d se v ere na usea, b ut n ot a S A E u nles s it meets t he criteria s h o w n i n Secti o n 6. 2 . 
O n t he ot her ha n d, a str o ke t hat res ul ts i n o nl y a li mite d de gree of disa bilit y ma y be c o nsi dere d 
a mil d str o ke b ut w o ul d be a S A E w he n it satisfies t he criteria s h o w n i n Secti o n 6. 2 . 
6. 3. 4  C a us alit y c ollecti o n  
T he I n vesti gat or  will assess ca usal relati o n shi p bet wee n I n vesti gati o nal Pr o d uct a n d eac h 
A d verse E ve nt, a n d  a ns wer ‘ yes’ or ‘ n o’ t o t he q uesti o n ‘ D o y o u c o nsi der t hat t h ere is a 
reas o na bl e p ossi bilit y t hat t he e ve nt ma y ha v e bee n ca use d b y t he i n vesti gati o nal pr o d uct?’ 
F or S A Es ca us al relati o ns hi p w ill als o be assesse d f or ot her me dicati o n a n d st u d y pr oce d ures. 
N ote t hat f or S A Es t hat c o ul d be ass ociate d wit h a n y st u d y pr oce d ure t he ca usal relati o ns hi p is 
i m plie d as ‘ yes’. 
A g ui de t o t he i nter pretati o n of t he ca us alit y q uesti o n is f o u n d i n A p pe n di x A  t o t he Cli nical 
St u d y Pr ot oc ol.  
6. 3. 5  A d verse e v e nts b ase d o n si g ns a n d s y m pt o ms  
All A Es s p o nta ne o usl y re p orte d b y t he 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 he st u d y site staff: or re v eale d b y o bser vati o n will be c ollecte d a n d rec or de d i n t he C R F. W he n 
c ollecti n g A Es, t he rec or di n g of dia g n oses is preferre d t o rec or di n g a list of si g ns a n d s y m pt o ms.  
H o we ver,  if a dia g n osis is k n o w n a n d t here are ot her si g ns or s y m pt o ms t hat are n ot ge nerall y 
part of t he dia g n o sis, t he dia g n osis a n d eac h si g n or s y m pt o m will be rec or de d se paratel y.  

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
3 1  (5 2 ) 
6. 3. 6  A d verse e v e nts b ase d o n e x a mi n ati o ns a n d tests  
T he res ults fr o m t he Cli nical Stu d y P r ot oc ol ma n date d la b orat or y tests a n d vital si g ns will be 
s u m marise d i n t he C S R .  Deteri or ati o n as c o m pare d t o baseli ne i n pr ot oc ol -ma n date d la b orat or y 
val ues a n d vital si g ns s h o ul d t heref ore o nl y b e re p orte d as A Es if t he y f ulfil a n y of t h e S A E 
criteria or are t he reas o n f or disc o nti n uati o n of treat me nt wit h t he i n vesti gati o nal pr o d uct. 
If det eri orati on i n a la b orat or y val u e/ vital si g n is ass ociate d wit h cli nical si g ns a n d s y m pt o ms, 
t he si g n or s y m pt o m will be re p orte d as a n A E a n d t he ass o ciate d la b orat or y res ult/ vital si g n 
will be c o nsi dere d as a d diti o nal i nf or mati o n.  W h ere ver p ossi ble t he re p orti n g I n vesti gat or us es 
t he cli nical, rat her t ha n t he la b orat or y ter m (e. g., a nae mia v ers us l o w hae m o gl o bi n val ue). I n 
t he a bse n ce of cli nical si g ns or s y m pt oms, cli nicall y rele va nt deteri orati o ns i n n o n -ma n date d 
para meters s h o ul d be re p orte d as A E(s).  
A n y ne w o r a g gra vate d cli nicall y rele va nt a b n or m al me dical fi n di n g at a p h ysical e xa mi nati o n 
as c o m pare d wit h t he bas eli ne assess me nt will be re p orte d as a n A E  
 
6. 4   Re p orti n g of seri o us a d verse e ve nts  
All S A Es ha ve t o be re p orte d, w het her or n ot c o nsi dere d ca us all y r elate d t o t he i n vesti gati o nal 
pr o d uct, or t o t he st u d y pr oce d ure(s). All S A Es will be rec or de d i n t he C R F.  
If a n y S A E occ urs i n t he c o urse of t he st u d y, t he n I n v esti gat ors or ot her site pers o n nel i nf or m 
t he a p pr o pri ate Astr a Ze n eca re prese ntati ves wit hi n o ne da y i. e., i m me diatel y  b ut n o l ater t h a n 
2 4 h o urs  of w he n he or s he bec o mes a ware of it . 
T he desi g nate d Astra Z e neca re prese ntati ve w or ks wit h t he I n ve sti gat or t o e ns ure t h at all t he 
necessar y i nf or mati o n is pr o vi de d t o t he Astra Ze neca Patie nt  Safet y data  e ntr y site wit hi n 1  
c ale n d ar d a y  of i nitial recei pt f or fatal a n d life t hr eate ni n g e v e nts a n d wit hi n 5 c ale n d ar  d a ys 
of i nitial recei pt f or all ot her S A Es.  
F or fatal or life -t hreate ni n g a d vers e e ve nts w here i m p orta nt or rele va nt i nf or mati o n is missi n g, 
acti ve f oll o w-u p is u n d erta ke n i m me diatel y.  I n vesti gat ors or ot her sit e pers o n nel i nf or m 
Astra Ze neca re pres e ntati ves of a n y f oll o w -u p i nf or mati o n o n a pr e vi o usl y re p orte d S A E wit hi n 
o ne cale n dar da y i. e., i m me diatel y b ut  n o l ater t h a n 2 4 h o urs of w he n he or  s he b ec o mes a ware 
of it . 
T he Astra Z e neca re prese ntati ve will a d vise t he I n vesti gat or/st u d y site staff h o w t o pr ocee d.  
6. 5   O ver d ose  
•  
A n o ver d os e wit h ass oci ate d A Es is rec or de d as t he A E dia g n osis/s y m pt o ms o n t he 
rele va nt A E m o d ules i n t he C R F a n d o n t he O v erd ose C R F m o d ule.  
•  
A n o ver d os e wit h o ut ass ociate d s y m pt o ms is o nl y re p orte d o n t he O ver d ose C R F 
m o d ule.  

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
3 2  (5 2 ) 
If a n o v er d ose o n a n Astra Ze neca st u d y dr u g occ urs i n t he c o urse of t he st u d y, t he n t he 
I n v esti gat or or ot h er site pers o n nel i nf or m a p pr o priat e 
Astra Z e n eca re prese ntati ves 
i m me diatel y, or n o l ater t h a n 2 4 h o urs  of w he n he or s he bec o mes a ware of it.  
If a n o ver d ose is s us pecte d, m o nit ori n g of vital f uncti o ns as well as treat me nt s h o ul d be perf or me d 
as a p pr o priate.  
T he desi g nat e d Astr a Ze neca re prese ntati ve w o r ks wit h t he I n v esti gat or t o e ns ure t hat all 
rele va nt i nf or m ati o n is pr o vi de d t o t he Astra Ze n eca Patie n t Safet y data e ntr y site.  
F or o ver d os es ass o ciate d wit h a S A E, t he sta n dar d re p orti n g ti meli nes a p pl y, see Secti o n 6. 4 .  
F or ot her o ver d oses, re p orti n g m ust occ ur wit hi n 3 0 da ys.  
6. 6   Pre g n a nc y  
A ll pre g na ncies a n d o utc o mes of pre g n a nc y s h o ul d be re p ort e d t o Astra Ze neca e xce pt f or:  
•  If t he pre g n a nc y is disc o vere d bef ore t h e st u d y s u bject has recei ve d a n y st u d y dr u g  
6. 6. 1  M ater n al e x p os ure  
If a s u bject b ec o mes pre g na nt d uri n g t he c o urse of t he st u d y i n vesti gati o nal pr o d uct s h o ul d be 
disc o nti n ue d i m me diatel y . 
Pre g na nc y itself is n ot re gar de d as a n a d verse e ve nt u nless t here is a s us pici o n t hat t he 
i n vesti gati o nal pr o d uct u n der st u d y 
ma y ha ve i nterfere d 
wit h t he effecti ve n ess of a 
c o ntrace pti ve me dicati o n.  C o n ge nital a b n or malities/ birt h defects a n d s p o nta ne o us miscarria ges 
s h o ul d be re p ort e d a n d h a n dle d as S A Es.  El ecti v e a b orti o ns wit h o ut c o m plicati o ns s h o ul d n ot 
be ha n dle d a s A Es.  T he o utc o me of all pre g na ncies (s p o nta ne o us miscarria ge, el ecti ve 
ter mi nati o n, ect o pic pre g na nc y, n or mal birt h or c o n ge nital a b n or malit y) s h o ul d be f oll o we d u p 
a n d d oc u me nte d e ve n if t he s u bject was disc o nti n ue d fr o m t he st u d y.  
If a n y pre g na nc y occurs i n t he c o urse of t he st u d y, t he n t he I n vesti gat or or ot her site p ers o n nel 
i nf or ms t he a p pr o priate Astra Ze neca re prese nt ati ves wit hi n 1 da y i. e., i m me diatel y b ut n o l at er 
t h a n 2 4 h o urs of  w he n he or s he bec o mes a ware of it . 
T he desi g nat e d Astr a Ze neca re p rese ntati ve w or ks wit h t he I n v esti gat or t o e ns ure t hat all 
rele va nt i nf or mati o n is pr o vi de d t o t he Astra Ze neca Patie nt  Safet y data e ntr y site wit hi n 1 or 5 
cale n dar da ys f or S A Es (see Secti o n 6. 4 ) a n d wit hi n 3 0 da ys f or all ot her pre g na ncies.  
T he sa me ti meli nes a p pl y w he n o utc o me i nf or m ati o n is a vaila ble.  
6. 7   Me di cati o n Err or  
F or t he p ur p os es of t his cli nical st u d y a me dicati o n err or is a n u ni nte n d e d fail ure o r mista ke i n 
t he treat me nt pr ocess f or a n Astra Z e neca stu d y dr u g t hat eit her ca uses h ar m t o t he s u bject or 
has t he p ote ntial t o ca use har m t o t he s u bject.  

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n  + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
3 3  (5 2 ) 
A me dicati o n err or is n ot lac k of efficac y of t he dr u g, b ut rat her a h u m a n or pr ocess relat e d 
fail ure w hile t he dr u g is i n c o ntr ol of t he st u d y site staff or s u bject. 
Me dicati o n err or i ncl u des sit uati o ns w here a n err or.  
•  occ urre d  
•  was i de ntifie d a n d i nterce pte d bef ore t he s u bject recei ve d t h e dr u g 
•  di d n ot occ ur, b ut circ u msta nces were rec o g nize t hat c o ul d ha ve le d t o a n err or  
E xa m ples of e ve nts t o be re p orte d i n cli nical st u dies as me dicati o n err ors: 
•  Dr u g na me c o nf usi o n  
•  Dis pe nsi n g err or e. g. me dicati o n pre pare d i nc orrectl y, e ve n if it was n ot act uall y gi ve n 
t o t he s u bject 
•  Dr u g n ot a d mi nistere d as i n di cate d, f or e x a m ple, wr o n g r o ute or wr o n g site of 
a d mi nistrati o n  
•  Dr u g n ot ta k e n as i n dicat e d e. g. ta blet diss ol ve d i n water w he n it s h o ul d b e ta ke n as a 
s oli d ta blet  
•  Dr u g n ot st ore d as i nstr ucte d e. g. k e pt i n t he fri d ge w he n it s h o ul d be at r o o m 
te m perat ure  
 
E xa m ples of e ve nts t hat d o n ot  re q uire re p orti n g as me dicati o n err ors i n cli nical st u dies:  
•  S u bject  acci de ntall y misse d dr u g d ose(s) e. g. f or g ot t o ta ke me dicati o n  
•  Acci de ntal o v er d ose ( will be ca pt ure d as a n o v er d ose)  
•  S u bject  faile d t o ret ur n u n use d me dicati o n or e m pt y pac ka gi n g 
•  Err ors rel ate d t o bac k gr o u n d a n d r esc ue me di cati o n, or sta n dar d of care me dicati o n i n 
o pe n la bel st u dies, e ve n if a n A Z pr o d u ct  
Me dicati o n err ors are n ot re gar de d as A Es b ut A Es ma y o cc ur as a c o nse q u e nce of t h e 
me dicati o n err or.   
If a ny  me dicati o n err or occ urs i n t he c o urse of t he st u d y , t he n t he I n v esti gat or or ot her site 
pers o n nel i nf or ms t h e a p pr o priate Astra Ze n eca re prese ntati ves wit hi n 1  da y i.e., i m me diatel y 
b ut n o l ater t h a n 2 4 h o urs of w he n h e or s he b ec o mes a ware of it.  
T he desi g nat e d Astr a Ze neca re prese ntati ve w or ks wit h t he  I nv esti gat or t o e ns ure t hat all 
rele va nt i nf or mati o n is c o m plete d wit hi n 1 or 5 cale n dar d a ys if t here is a n S A E ass ociate d wit h 
t he me dicati o n err or (see Secti o n 6. 4 ) a n d wit hi n 3 0 da ys for all ot her m e dicati o n e rr ors. 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
3 4  (5 2 ) 
7  I N V E S TI G A TI O N A L P R O DU C T A N D O T H E R T R E A T M E N T S  
7. 1   I de ntit y of i n vesti g ati o n al pr o d uct(s) 
 
I n vesti g ati o n al pr o d uct 
D os a ge f or m a n d stre n gt h  
M a n uf act urer  
da pa glifl ozi n/ sa xa gli pti n  
fil m-c oate d ta blets, 1 0 m g/ 5  
m g  
Astra Ze neca  
 
 
 
 
7. 2   D ose a n d tre at me nt r e gi me ns 
T he I P s h o ul d be ta ke n o nce dail y at a p pr o xi matel y t he sa me ti me of t he da y d uri n g t he st u d y 
peri o d .  T he I P s h o ul d n ot be altere d (e g, cr us he d, p ut i n a n ot her ve hicle) a n d s h o ul d n ot be 
gi ve n b y nas o gastric t u be or ot her r o utes.  
7. 3   L a belli n g  
La bels  will be pre p are d i n acc or da nce wit h G o o d Ma n ufact uri n g Practice ( G M P) a n d l ocal 
re gulat or y g ui deli nes.  T he la bels will f ulfil G M P A n ne x 1 3 re q uir e me nts f or la belli n g.   
7. 4   St or a ge  
All st u d y dr u gs s h o ul d be ke pt i n a sec ure place u n der a p pr o priate st or a ge c o n diti o ns.  A 
descri pti o n of t he a p pr o priate st ora ge c o n diti o ns is s pecifie d o n t he  i n vesti gati o nal pr o d uct pac k 
la bel. 
7. 5   C o m pli a nce  
T he a d mi nistrati o n of all st u d y dr u gs (i ncl u di n g i n vesti gati o nal pr o d ucts) s h o ul d be rec or de d  
i n t he a p pr o priate secti o ns of t he e C R F. S u bjects will be as ke d t o ret ur n all u n use d 
i n vesti gati o nal pr o d uct a n d e m pt y pac ka ges a n d b ottles t o t he cli nic at eac h visit. T he s u bject 
will be as ke d a b o ut c o m plia nce at eac h st u d y  visit; c o m plia nce will als o be assesse d b ase d o n 
ret ur ne d t a blet c o u nts. T a blet c o u nts will be rec or de d i n t he e C R F. S u bjects j u d ge d t o be n o n-
c o m plia nt ( defi ne d as ta ki n g less t ha n 8 0 %  or m ore t ha n 1 2 0 % of t he prescri be d d ose of 
i n vesti gati o nal pr o d uct) ma y c o nti n ue i n t he st u d y, b ut s h o ul d be c o u nsell e d o n t he i m p orta nce 
of ta ki n g t heir st u d y me dicati o n as  prescri be d . 
 
7. 6  Acc o u nt a bilit y  
 
St u d y dr u g will n ot be distri b ute d t o t he st u d y site u ntil t he c o ntr act is c o n cl u de d bet w ee n t h e  
st u d y site a n d Astra Ze n eca/ D ele gate. T h e I n v esti gat or/ Site is res p o nsi ble f or ma na gi n g t he 
st u d y dr u g fr o m recei pt b y t he i nstit uti o n u ntil t he ret ur n of all u n use d st u d y  dr u g t o 
Astra Ze neca / del e gate. Astra Ze neca will pr o vi de t he st u d y d oc u me nts ‘ Pr oce d ures f or dr u g 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
3 5  (5 2 ) 
acc o u nta bilit y’ a n d ‘ Pr o ce d ures f or dr u g st ora g e’ w hic h des cri bes t h e s p ecific re q uire m e nts. 
T he i n vesti gat or(s) is res p o ns i ble f or e ns uri n g t hat t he s u bject has ret ur n e d all u n use d st u d y 
dr u g.  
 
7. 7   C o nc o mit a nt a n d ot her tre at me nts  
C ha n ges i n c o nc o mita nt me dicati o n s h o ul d be a v oi de d d uri n g st u d y partici pati o n, wit h t he  
e xce pti o n of sit uati o ns d efi ne d i n t his pr ot oc ol, b ut me dicati o n, w hic h is c o nsi dere d necessar y  
f or t he s u bject’s safet y a n d well-bei n g, ma y be gi ve n at t he discreti o n of t he i n vesti gat ors,  w h o 
m ust deci de if t he s u bject s h o ul d re mai n i n st u d y or nee d t o be dis misse d fr o m st u d y d ue  t o 
s u bject’s safet y or i nterfere nce wit h st u d y o bjecti ves. 
T he a d mi nistrati o n of all me dicati o n m ust be rec or de d i n t he a p pr o pri ate secti o ns of t he  
electr o nic case re p ort f or m (e C R F) wit h tra de na mes, d osa ges, dates of st arti n g a n d  e n di n g of  
me dicati o n a n d reas o n f or t hera p y.  If t he patie nts gl yce mic stat us re mai ns u nc o ntr olle d  (H b A 1c 
≥ 9 %, F B G ≥ 2 4 0 m g/ dl ( c o nfir m e d o n r e a di n g s t a k e n o n 2 c o n s e c uti v e d a y s)  
 
After h a vi n g c o m plete d or disc o nti n ue d t he st u d y, i n vesti gati o nal pr o d uct will be disc o nti n ue d 
fr o m s p o ns or b ut s u bjects will recei ve us ual care a n d a nti dia betic a ge nts acc or di n g t o t he 
i n vesti gat or's j u d ge me nt a n d acc or di n g t o l ocal m e dical practice.  
 
Pr o hi bite d T her a pies  
 
•  Wei g ht l oss 
me dicati o n, i ncl u di n g b ut n ot li mite d t o 
mazi n d ol, si b utra mi ne, 
p he nter mi ne, orlistat, ri m o na ba nt, be nz p heta mi n e, diet h yl pr o pri o n, met ha m p heta mi ne, 
an d/ or  he n di metrazi ne  
•  A nti viral dr u gs ( dela vir di ne, i n di na vir, nelfi na vir , rit o na vir, sa q ui na vir) 
•  Treat me nt wit h s yste mi c gl uc oc ortic oi ds e q ui v ale nt t o oral pre d nis ol o ne ≥1 0 m g 
( beta metas o n e ≥1. 2 m g, de xa met has o ne ≥1. 5 m g, h y dr oc ortis o ne ≥4 0 m g) per da y (tw o 
te m p orar y peri o ds of hi g her dail y d oses f or n o l o n ger t ha n 7 da ys eac h are all o we d).  
•  A nti -dia be tic a ge nts e x ce pt f or t he st u d y me dicati o n, a basal a nti-dia betic a ge nts 
me dicati o n a n d resc ue t h era pies ( A nti -dia betic a g e nts pla n ne d t o be st o p pe d f or was h -
o ut are all o we d t o be use d u ntil t he be gi n ni n g of was h -o ut peri o d. Aft er c o m pleti o n of 
t he treat ment p eri o d, alter nati ve a nti -dia betic treat me nt will be i nitiate d acc or di n g t o 
sta n dar d me dic al practice.) 
 
7. 7. 1  Ot her c o nc o mit a nt tre at me nt  
Ot her me dicati o n ot her t ha n t hat descri be d a b o ve, w hic h is c o nsi dere d necessar y f or t he 
s u bject’s safet y a n d w ell bei n g , ma y be gi ve n at t he discreti o n of t h e I n vesti gat or a n d rec or de d 
i n t he a p pr o priate s ecti o ns of t he Case Re p ort F or m. 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
3 6  (5 2 ) 
8  S T A TI S TI C A L A N A L Y S E S  B Y A S T R A Z E N E C A   
T his is a n I n dia re g ulat or y re q uire me nt st u d y. O bjecti ve is t o esta blis h t hat F D C of 
Da pa glifl ozi n 1 0 m g  / Sa xa gli pti n 5 m g is a safe treat me nt o pti o n i n I n dia n T 2 D M patie nts. T his 
st u dy  is pla n ne d as pr os p ecti ve  st u d y o n 2 0 0  p atie nts i n si n gle  ar m o pe n la bel st u d y.  
 
 
 
 
Data will be s u m mariz e d usi n g descri pti ve statistics. C o nti n u o us varia bles will be s u m marize d 
usi n g t he n u m ber  of o bser vati o ns, mea n, S D, me dia n, a n d ra n ge as a p pr o priate. Cate g orical 
val ues will be s u m marize d usi n g t he n u m ber of o bser vati o ns a n d perce nt a g es as a p pr o priate.  
T he safet y a nal ysis p o p ulati o n will i ncl u de all patie nts w h o si g n t he I C F a n d recei ve at le ast 
o ne d ose of st u d y me d icati o n. 
T he safet y a n al ysis p o p ulati o n is als o a p plica ble t o t he efficac y a nal ysis, a n d a n y efficac y 
meas ure me nts c ollecte d bef ore t he st u d y me dicati o n disc o nti n uati o n will be i ncl u de d. Last o n 
treat me nt o bser vati o n will be carrie d f or war d t o i m p ute t he m issi n g data at wee k 2 4. 
 
A n y A E occ urri n g wit hi n 2 wee ks of disc o nti n uati o n of i n vesti gati o nal pr o d uct (ie, t he last d os e 
of st u d y me dicati o n) will be i ncl u de d i n t he A E s u m maries. A n y e ve nts i n t his peri o d t hat occ ur 
after a p atie nt has recei ve d f urt her t hera p y f or (f oll o wi n g disc o nti n uati o n of st u d y dr u g) will be 
fla g ge d i n t he dat a listi n gs. A d verse e ve nt rates s hall be stratifie d b y a ge/ ge n der/ baseli ne 
me dicati o ns. A n n ualise d e ve nt rate s hall als o b e prese nte d i n a d diti o n t o t he i nci de nce rat e 
d uri n g t h e st u d y. Mea n c ha n ge i n H b A 1 C fr o m baseli ne t o 6 m o nt hs f or patie nts will be 
a nal yse d usi n g paire d t test / Wilc o x o n si g ne d -ra n k test at 5 % le vel of si g nifica nce. 
T he st u d y is desi g ne d i n acc or da nce wit h t he Healt h A ut h orit y re q uire me nts i n I n dia. It is 
i nte n de d t o pr o vi de i nf or mati o n re gar di n g t he s afet y pr ofile f or patie nts i n I n dia, a n d will 
c o ntri b ute a d diti o nal i nf or mati o n t o t he o verall safet y pr ofile of Da p a -Sa xa F D C. D ue t o t he 
s mall sa m ple size, t his st u d y s h o ul d n ot be directl y c o m pare d t o t he d at a fr o m a n y ot her c o u ntr y.  
9  S T U D Y A N D D A T A M A N A G E M E N T B Y A S T R A Z E N E C A  
9. 1   Tr ai ni n g of st u d y site st aff 
Bef ore t he first s u bject is e ntere d i nt o t he st u d y, a n Astra Z e neca re prese ntati ve/ dele gate will 
re vie w a n d disc uss t he re q uire me nts of t he Cli nical St u d y Pr otoc ol a n d relate d d oc u me nts wit h 
t he i n vesti gati o nal staff a n d als o trai n t he m i n a n y st u d y s pecific pr oce d ures a n d electr o nic d at a 
c a pt ure s yste m(s) utilise d. 
C CI

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m be r 2 0 2 0 
3 7  (5 2 ) 
T he Pri nci pal I n v esti gat or will e ns ure t hat a p pr o priate trai ni n g rele va nt t o t he st u d y is gi ve n t o 
all of t hese staff, a n d t hat a n y ne w i nf or mati o n rele va nt t o t he perf or ma nce of t his st u d y is 
f or war de d t o t he staff i n vol ve d.  
T he Pri nci pal I n vesti gat or will mai ntai n a rec or d of all i n di vi d uals i n v ol ve d i n t he st u d y 
( me dical, n ursi n g a n d ot h er staff). 
9. 2   M o nit ori n g of t he st u d y  
D uri n g t he st u d y, a n Astra Ze n eca re pres e ntati ve / dele gate will ha ve re g ular c o ntacts wit h t he 
st ud y site, i ncl u di n g visits t o:  
•  
Pr o vi de i nf or mati o n a n d s u p p ort t o t he I n v esti gat or(s)  
•  
C o nfir m t hat facilities re mai n acce pta ble  
•  
C o nfir m  t hat t he i n vesti gati o nal tea m is a d heri n g t o t he Cli nical St u d y 
P r ot oc ol, t hat data are b ei n g acc uratel y a n d ti mel y rec ord e d i n t he eC R F, 
t hat bi ol o gical sa m ples are h a n dle d i n acc or da n ce wit h t he L a b orat or y 
Ma n ual a n d t hat st u d y dr u g acc o u nta bilit y c hec k s are bei n g p erf or me d 
•  
Perf or m s o urce data v erificati o n (a c o m paris o n of t he data i n t he eC R F 
wit h t he s u bject’s m e dical rec or ds at t he h os pital or practice, a n d ot her 
rec or ds rele va nt t o t he st u d y) i ncl u di n g verificati o n of i nf or me d c o nse nt of 
partici pati n g s u bjects. T his will re q uire direct access t o all ori gi nal rec or ds 
f or eac h s u bject (e. g., cli nic c harts) 
•  
E ns ure wit h dra wal of i nf or me d c o nse nt t o t he use of t he s u bject’s 
bi ol o gical sa m ples is re p orte d a n d bi ol o gical sa m ples are i de ntifie d a n d 
dis p ose d o f/ destr o ye d acc or di n gl y, a n d t he acti o n is d oc u me nte d, a n d 
re p orte d t o t he s u bject. 
T he Astra Z e neca re prese ntati ve will be a vaila ble bet wee n visits if t he I n v esti gat or(s) or ot her 
staff at t he ce ntre n ee ds i nf or mati o n a n d a d vice a b o ut t he st u d y c o n d uct.  
9. 2. 1  S o urce d at a  
Refer t o t he Cli nical St u d y A gree me nt f or l ocati o n of s o urce d ata.  
9. 2. 2  St u d y a gree me nts  
T he Pri nci pal I n vesti gat or at eac h/t he ce ntre s h o ul d c o m pl y wit h all t he ter ms, c o n diti o ns, a n d 
o bli gati o ns of t he Cli nical St u d y A gree me nt, or e q ui vale nt, f or t h is st u d y.  I n t he e ve nt of a n y 
i nc o nsiste nc y bet wee n t his Cli nical St u d y Pr ot oc ol a nd t he Cli nical St u d y A gree me nt, t he ter ms 
of Cli nical St u d y Pr ot oc ol s hall pre vail wit h res p ect t o t he c o n d u ct of t h e st u d y a n d t he treat me nt 
of s u bjects a n d i n all ot her res pects, n ot rel ati n g t o st u d y c o n d uct or tr eat me nt of s u bjects, t he 
ter ms of t he Cli nical St u d y A gree me nt s h all pre v ail. 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
3 8  (5 2 ) 
9. 2. 3  Arc hi vi n g of st u d y d oc u me nts  
T he I n vesti gat or f oll o ws t he pri nci ples o utli ne d i n t he Cli nical St u d y A gree me nt ( C S A).  
9. 3    St u d y ti met a bl e a n d e n d of st u d y 
T he e n d of t he st u d y is d efi ne d as ‘t h e last visit of t he last s ubject  u n der g oi n g t he st u d y ’. 
T he st u d y ma y be ter mi nate d at i n di vi d ual ce ntres if t he st u d y pr oce d ures are n ot bei n g 
perf or me d acc or di n g t o G C P, or if recr uit me nt is sl o w.  Astra Ze neca ma y als o ter mi nate t he 
e ntire st u d y pre mat urel y if c o ncer ns f or safet y aris e wit hi n t his st u d y or i n a n y ot her st u d y wit h 
Da pa glifl ozi n / sa xa gli pti n fi xe d d ose c o m bi nati o n. 
9. 4    D at a m a n a ge me nt b y dele g ate  
Data ma na ge me nt will be perf or me d b y  exter n al part ner , acc or di n g t o t he Data Ma na ge me nt 
Pla n . 
T he data c ollecte d t hr o u g h t hir d part y s o urces will be o btai ne d a n d rec o ncile d a gai nst st u d y 
data.  
A d verse e ve nts a n d me di cal/s ur gical hist or y will be classifie d acc or di n g t o t he ter mi n ol o g y of 
t he latest v ersi o n t he Me dical Dicti o nar y f or Re g ulat or y Acti vities ( Me d D R A).  M edicati o ns 
will be classifie d acc or di n g t o t he  W H O Dr u g Dicti o nar y .   
Data q ueries will be raise d f or i nc o nsiste nt, i m p ossi ble or missi n g data.  All e ntries t o t he st u d y 
data base wil l be a vaila bl e i n a n a u dit trail. 
T he data will be v ali date d as defi ne d i n t h e Dat a Ma na ge me nt Pla n.  Q ualit y c o ntr ol pr oce d ures 
will be a p plie d t o eac h sta ge of data ha n dli n g t o e ns ure t hat all data are reli a ble a n d ha ve b ee n 
pr ocesse d c orrectl y.  T he Dat a M a na g e me nt Pla n will als o clarif y t he r ol es a n d res p o nsi bilities 
of t he v ari o us f u n cti o ns a n d pers o n nel i n v ol ve d i n t he data ma na g e me nt pr o cess . 
W he n all data ha ve bee n c o de d, v ali date d, a n d l oc ke d, clea n file will be declare d.  A n y tr eat me nt 
re veali n g dat a ma y t hereafter be a d de d a n d t he fi n al data base will be l oc ke d.  
Seri o us A d verse E ve nt ( S A E) Rec o ncili ati o n  
S A E rec o nciliati o n re p orts are pr o d uce d a n d rec o n cile d wit h t he Patie nt  Safet y data base a n d/ or 
t he i n vesti gati o nal site.  
1 0    E T HI C A L A N D R E G U L A T O R Y  R E Q UI R E M E N T S  
1 0. 1  Et hic al c o n d uct of t he st u d y  
T he st u d y will b e perf or me d i n acc or da nce wit h et hical pri nci ples t hat h a ve t heir ori gi n i n t he 
Declarati o n of H elsi n ki a n d are c o nsiste nt wit h I C H/ G o o d Cli nical Practice, a p plica bl e 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
3 9  (5 2 ) 
re g ulat or y re q uir e me nts a n d t he Astra Ze neca p olic y o n Bi oet hics a n d H u ma n  Bi ol o gical 
Sa m ples.  
1 0. 2  S u bject  d at a pr otecti o n  
T he I nf or m e d C o nse nt F or m will i nc or p orate ( or, i n s o me cases, be acc o m pa nie d b y a se parate 
d oc u me nt i nc or p orati n g) w or di n g t hat c o m plies wit h rele va nt data pr otecti o n a n d pri vac y 
le gislati o n. 
1 0. 3  Et hics a n d re g ul at or y re vie w  
A n Et hics C o m mittee m ust  a p pr o ve t he fi nal Cli nical St u d y P r ot oc ol, i ncl u di n g t he fi nal versi o n 
of t he I nf or me d C o nse nt F or m a n d a n y ot her writte n i nf or mati o n a n d/ or mat erials t o be pr o vi de d 
t o t he s u bjects.  T h e I n vesti gat or will e ns ure t he distri b uti o n of t hese d oc u me nts t o t he 
a p plica ble Et hics C o m mittee, a n d t o t he st u d y site staff.  
T he o pi ni o n of t he Et hics C o m mittee s h o ul d be gi ve n i n writi n g. T he I n vesti gat or s h o ul d s u b mit 
t he writte n a p pr o val t o Astra Ze neca bef ore e nr ol m e nt of a n y s u bject i nt o t h e st u d y.  
T he Et hics C o m mittee s h o ul d a p pr o ve all a d v ertisi n g use d t o recr uit s u bjects f or t he st u d y. 
Astra Ze neca s h o ul d a p pr o ve a n y m o dificati o ns t o t he I nf or m e d C o nse nt F or m t hat are nee de d 
t o meet l ocal re q uir e me nts. 
Bef ore e nr ol me nt of a n y s u bject i nt o t he st u d y, t he fi nal Cli nical St u d y P r ot oc ol, i ncl u di n g t he 
fi nal versi o n of t he I nf or me d C o nse nt F or m, is a p pr o ve d b y t he nati o nal r e g ulat or y a ut h orit y. 
Astra Ze neca will ha n dle t he distri b uti o n of a n y of  t hese d oc u me nts t o t he nati o nal re g ulat or y 
a ut h orities. 
Astra Ze neca 
will pr o vi de 
Re g ulat or y 
A ut h orities, 
Et hics 
C o m mittees a n d 
Pri nci pal 
I n v esti gat ors wit h safet y u p dates/re p orts acc or di n g t o l ocal re q uire m e nts. 
 
1 0. 4  I nf or me d c o nse nt 
T he Pri nci pal I n vesti gat o r(s) at e ac h ce ntre will:  
•  
E ns ure eac h s u bject is gi ve n f ull a n d a d e q uate oral a n d writte n i nf or mati o n 
a b o ut t he nat ure, p ur p ose, p ossi ble ris k a n d be nefit of t he st u d y  
•  
E ns ure eac h s u bject is n otifie d t hat t he y are free t o disc o nti n ue fr o m t he 
st u d y at a n y ti me 
•  
E ns ure t hat eac h s u bject  is gi ve n t he o p p ort u nit y t o as k q uesti o ns a n d 
all o we d ti me t o c o nsi der t he i nf or mati o n pr o vi de d  

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
4 0  (5 2 ) 
•  
E ns ure eac h s u bject pr o vi des si g ne d a n d date d i nf or me d c o ns e nt bef ore 
c o n d ucti n g a n y pr oce d ure s pecificall y f or t he st u d y  
•  
E ns ure t he ori gi nal, si g ne d I nf or m e d C o nse nt F or m(s) is/are st or e d i n t he 
I n v esti gat or’s St u d y File 
•  
E ns ure a c o p y of t he si g ne d I nf or me d C o nse nt F or m is gi ve n t o t he s u bject 
•  
E ns ure t hat a n y i nce nti ves f or s u bjects w h o p artici pate i n t he st u d y as well 
as a n y pr o vis i o ns f or s u bjects har me d as a c o nse q ue nce of st u d y 
partici pati o n are descri be d i n t he i nf or me d c o nse nt f or m t hat is a p pr o ve d 
b y a n Et hics C o m mittee.  
1 0. 5  C h a n ges t o t he  Cli nic al St u d y Pr ot oc ol a n d I nf or me d C o nse nt F or m  
If t here are a n y s u bsta ntial c ha n ges t o t he Cli nical St u d y P r ot oc ol, t he n t hese c ha n g es will be 
d oc u me nte d i n a ne w versi o n of t he st u d y pr ot oc ol.  
T he ne w v ersi o n of t he Cli nical St u d y P r ot oc ol is t o be a p pr o ve d b y t he rele va nt Et hics 
C o m mittee a n d  als o t he nati o nal re g ulat or y a ut h orit y a p pr o val, bef ore i m ple me ntati o n.  L o cal 
re q uire me nts are t o be f oll o we d f or ne w versi o ns of Cli nical St u d y P r ot oc ols. 
Astra Ze neca will distri b ute a n y ne w versi o ns of t he Cli nical St u d y P r ot oc ol t o eac h Pri nci pal 
I n v esti gat or(s). F or distri b uti o n t o Et hics C o m mittee see Secti o n 1 0. 3 . 
If a c ha n g e t o a Cli nical St u d y P r ot oc ol re q uir es a c ha n ge t o a ce ntre’s I nf or me d C o nse nt F or m, 
Astra Ze neca a n d t h e ce ntre’s Et hics C o m mittee are t o a p pr o ve t he re vise d I nf or me d C o nse nt 
F or m be f ore t he re vise d f or m is use d.  
1 0. 6  A u dits a n d i ns pecti o ns  
A ut h orise d re prese ntati v es of Astra Ze n eca  or dele gate,  a re g ul at or y a ut h orit y, or a n Et hics 
C o m mittee ma y perf or m a u dits or i ns pecti o ns at t he ce ntr e, i ncl u di n g s o urce dat a verificati o n.  
T he p ur p ose o f a n a u dit or i ns pecti o n is t o s yste maticall y a n d i n de pe n de ntl y e xa mi ne all st u d y-
relate d acti vities a n d d oc u me nts, t o deter mi ne w het her t hese acti vities were c o n d ucte d, a n d dat a 
were rec or de d, a nal yse d, a n d acc urat el y re p ort e d acc or di n g t o t he Cli nical St u d y Pr ot oc ol , G o o d 
Cli nical Practice ( G C P), g ui deli nes of t he I nter nati o nal C o nfere nce o n Har m o nisati o n (I C H), 
a n d a n y a p plica ble re g ulat or y re q uir e me nts.  T he I n vesti gat or will c o ntact Astra Z e neca 
i m me diatel y if c o ntacte d b y a re g ulat or y a ge n c y a b o ut a n ins pecti o n at t he ce ntre.  
 
 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
4 1  (5 2 ) 
 
1 1    LI S T O F R E F E R E N C E S  
 
1.  I nter nati o nal Dia b etes Fe derati o n. I D F Dia b etes Atlas, 8t h e d n. Br ussels, Bel gi u m: 
       I nter nati o nal Dia b etes Fe derati o n, 2 0 1 7. 
2.  Ra mac ha n dra n A, Das A, J os hi S, Yaj ni k C, S ha h S,  K u mar K P. C urre nt stat us of 
dia betes i n I n dia a n d n ee d f or n o vel t hera pe utic a ge nts. J Ass oc P h ysicia ns I n dia. 
2 0 1 0; 5 8: 7 -9.  
3.  J os hi S R, B ha nsali A, Bajaj S, Ba nzal S S, D har mali n ga m M, G u pta S, et al. Res ults fr o m 
a dietar y s ur v e y i n a n I n dia n T 2 D M p o p ula ti o n: a S T A R C H st u d y. B MJ O pe n. 
2 0 1 4; 4( 1 0).  
4.  Pl os ker G L. Da pa glifl ozi n: a re vie w of its use i n patie nts wit h t y pe 2 dia betes. Dr u gs. 
2 0 1 4; 7 4( 1 8): 2 1 9 1 -2 0 9.  
5.  Dea n na S. K a nia et al, Sa xa gli pti n: A Cli nical Re vie w i n t he Treat me nt of T y pe 2  
Dia betes Mellit us. Cli nical T hera p e utics/ V ol u me 3 3, N u m ber 8, 2 0 1 1 . 
6.    Q T E R N [ pac k a ge i nsert]. Wil mi n gt o n,  D E: Astra Ze neca P har m ace uticals L P;  2 0 1 9  
7.  Bl o n de L, Sa n J ua n Z T. Fi xe d -d os e c o m bi nati o ns f or treat me nt of t y p e 2 dia betes mellit us. 
A d v T her. 2 0 1 2; 2 9( 1): 1 – 1 3.  
 
 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
4 2  (5 2 ) 
A p pe n di x A  
A d diti o n al S afet y I nf or m ati o n 
F urt her G ui d a nce o n t he Defi niti o n of a Seri o us A d verse E ve nt ( S A E)  
Life t hre ate ni n g  
‘ Life-t hr eate ni n g’ me a ns t hat t he s u bject was at i m me diate ris k of deat h fr o m t he A E  as it 
occ urre d or it is s us pecte d t hat use or c o nti n ue d use of t he pr o d u ct  w o ul d res ult i n t he 
s u bject’s deat h.  ‘ Life-t hr eate ni n g’ d oes n ot mea n t hat ha d a n A E  occ urre d i n a m ore se vere 
f or m it mi g ht ha ve ca use d deat h (e. g., h e patitis t hat res ol ve d wit h o ut he patic fail ure). 
H os pit alis ati o n  
O ut s u bject treat me nt i n a n e mer ge n c y r o o m is n ot i n itself a seri o us A E, alt h o u g h t he reas o ns 
f or it ma y be (e. g., br o nc h os pas m, lar y n geal oe de ma).  H os pital a d missi o ns a n d/ or s ur gical 
o perati o ns pla n ne d b ef ore or d uri n g a st u d y are n ot c o nsi dere d A Es  if t he ill ness or disease 
e xiste d bef ore t he s u bject was e nr olle d i n t he st u d y, pr o vi de d t hat it di d n ot deteri orat e i n a n 
u ne x pecte d wa y d uri n g t he st u d y.  
I m p ort a nt me dic al e ve nt or me dic al i nter ve nti o n 
Me dical a n d sci e ntific j u d ge m e nt s h o ul d be e xercise d i n deci di n g w h et her a case is seri o us i n 
sit uati o ns w here i m p orta nt me dical e ve nts ma y n ot be i m me diatel y life t hreate ni n g or res ult i n 
deat h, h os pitalisati o n, disa bilit y or i nca pacit y b ut ma y je o par dize t he s u bject or ma y re q uir e 
m e dical i nter ve nti o n t o pre ve nt o ne or m ore o utc o mes liste d i n t he defi niti o n of seri o us.  
T hese s h o ul d us uall y be c o nsi dere d as seri o us.  
Si m pl y st o p pi n g t he s us pect dr u g d oes n ot mea n t hat it is a n i m p orta nt me dical e ve nt; me dical 
j u d ge me nt m ust be use d. 
•  
A n gi oe de ma n ot se vere e n o u g h t o re q uire  i nt u bati o n b ut re q uiri n g i v h y dr oc ortis o ne 
treat me nt 
•  
He pat ot o xicit y ca use d b y paraceta m ol (aceta mi n o p he n) o ver d ose re q uiri n g treat me nt 
wit h N -acet ylc yst ei ne  
•  
I nte nsi v e treat me nt i n a n e mer ge n c y r o o m or at h o me f or aller gi c br o nc h os pas m 
•  
Bl o o d d yscrasias ( e. g., n e utr o pe nia or a nae mia re q uiri n g bl o o d tra nsf usi o n, etc.) or 
c o n v ulsi o ns t hat d o n ot res ult i n h os pitalisati o n  
De vel o p me nt o f dr u g d e pe n de nc y or dr u g a b us e 
A G ui de t o I nter preti n g t he C a us alit y Q uesti o n  
W he n ma ki n g  a n assess me nt of ca usal it y c o nsi der the f oll o wi n g fact ors w he n deci di n g if t here 
is a ‘reas o n a ble p ossi bilit y’  t hat a n A E ma y ha ve b ee n ca use d b y t he dr u g. 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
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Date 2 2 Se pte m ber 2 0 2 0  
4 3  (5 2 ) 
•  
Ti me C o urse.  E x p os ure t o s us pect dr u g.  Has t he s u bject act uall y recei ve d t he s us pect 
dr u g?  Di d t he A E o cc ur i n a reas o n a ble te m p oral relati o ns hi p t o t he a d mi nistrati o n of 
t he s us pect dr u g? 
•  
C o nsiste nc y wit h k n o w n dr u g pr ofile.  Was t he A E c o nsiste nt wit h t he pre vi o us 
k n o wle d ge of t he s us p ect dr u g ( p har mac ol o g y a n d t o xic ol o g y) or dr u gs of t he sa me 
p har mac ol o gical class? Or c o ul d t he A E b e a ntici pate d fr o m its p har mac ol o gical 
pr o perties?  
•  
De -c h alle n ge  e x p erie n ce.  Di d t he A E res ol ve or i m pr o ve o n st o p pi n g or re d uci n g t he 
d ose of t he s us pect dr u g?  
•  
N o alter nati ve ca use.  T h e A E ca n n ot b e reas o na bl y e x plai ne d b y a n ot her aeti ol o g y 
suc h as t he u n derl yi n g disease, ot her dr u gs, ot her h ost or e n vir o n me ntal fact ors.  
•  
Re -c halle n g e  e x perie nce.  Di d t he A E re o cc ur if t h e s us pecte d dr u g was rei ntr o d uce d 
after ha vi n g bee n st o p pe d? Astra Ze n eca w o ul d n ot n or mall y rec o m me n d  or s u p p ort a 
re-c h alle n ge . 
•  
La b orat or y tests.  A s p ecific la b orat or y i n vesti gati o n (if perf or me d) has c o nfir me d t he 
relati o ns hi p. 
I n diffic ult cas es, ot her fact ors c o ul d be c o nsi dere d s uc h as: 
•  
Is t his a rec o g niz e d feat ure of o ver d ose of t h e dr u g? 
•  
Is t here a k n o w n mec h a nis m?  
Ca usa lit y of ‘relate d’ is ma de if f oll o wi n g a re vie w of t he rel e va nt data, t h ere is e vi de n ce f or a 
‘reas o n a ble p ossi bilit y’  of a ca us al relati o ns hi p f or t he i n di vi d ual case.  T he e x pressi o n 
‘reas o n a ble p ossi bilit y’ of a ca us al relati o ns h i p is mea nt t o c o n ve y, in ge n eral, t hat t here are 
facts (e vi d e nce) or ar g u me nts t o s u g gest a ca usal relati o ns hi p. 
T he ca us alit y assess me nt is perf or me d b ase d o n t h e a vaila ble data i ncl u di n g e n o u g h 
i nf or mati o n t o ma ke a n i nf or me d j u d g me nt.  Wit h li mite d or i ns ufficie nt i nf or mati o n i n t he 
case, it is li kel y t hat t he e ve nt(s) will be assess e d as ‘ n ot relate d’.  
Ca usal relati o ns hi p i n cases w here t he diseas e u n der st u d y has deteri orate d d ue t o lac k of 
effect s h o ul d be classifie d as n o reas o n a ble p ossi bilit y

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
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4 4  (5 2 ) 
 
A p pe n di x B  
Acti o ns Re q uire d i n C ases of I ncre ases i n Li ver Bi oc he mistr y 
a n d E v al u ati o n of H y’s L a w  
1. I ntr o d ucti o n  
T his A p pe n di x descri bes t he pr ocess t o be f oll o we d i n or der t o i de ntif y a n d a p pr o priatel y re p ort 
cases of H y’s La w.  It is n ot i nte n de d t o be a c o m pre he nsi ve g ui de t o t he ma na ge me nt of 
ele vate d li ver bi o c he mistries.   
D uri n g t he c o urs e of t he st u d y t he I n v esti gat or will re mai n vi gila nt f or i ncreases i n li ver 
bi oc he mistr y.  T he In vesti gat or is res p o nsi ble  f or d eter mi ni n g w het her a s u bject meets p ote ntial 
H y’s La w ( P H L) criteria at a n y p oi nt d uri n g t he st u d y.  
T he I n vesti gat or p artici p ates, t o get her wit h Astra Ze neca cli nical pr oject re prese ntati ves, i n 
re vie w a n d assess me nt of cases me eti n g P H L criteria t o a gree w het h er H y’s La w ( H L) criteria 
are met.  H L criteria are met if t here is n o alter nati ve e x pla nati o n f or t h e el e vati o ns i n li ver 
bi oc he mistr y ot her t ha n  Dr u g I n d uce d Li ver I nj ur y ( DI LI) ca us e d b y t he I n vesti gati o nal 
Me dici nal Pr o d uct (I P).  
T he I n vesti gat or is r es p o nsi ble f or rec or di n g data perta i ni n g t o P H L/ H L cases a n d f or re p orti n g 
A d verse E v e nts ( A E) a n d Seri o us A d verse E v e nts ( S A E) acc or di n g t o t he o utc o me of t he re vie w 
a n d assess me nt i n li ne wit h sta n dar d safet y re p orti n g pr ocesses.  
2. Defi niti o ns  
P ote nti al H y’s L a w ( P H L)  
As partate A mi n otra n sferase ( A S T) or Ala ni ne A mi n otra nsferas e ( A L T) ≥ 3 x U p per Li mit of 
N or mal ( U L N) t o get her wit h T otal Bilir u bi n ( T B L) ≥ 2 x U L N at a n y p oi nt d uri n g t he st u d y 
f oll o wi n g t he start of st u d y me dicati o n  irres pecti ve of a n i ncreas e i n Al kali ne P h os p hatase 
( A L P).  
H y’s L a w ( H L)  
A S T or A L T ≥ 3 x U L N  t o get her wit h T B L ≥ 2 x U L N, w here n o ot her reas o n, ot her t ha n t he 
I M P, ca n be f o u n d t o e x plai n t he c o m bi nati o n of i ncreas es, e. g., el e vate d A L P i n dicati n g 
c h olestasis, viral he patitis, a n ot her dr u g.   
F or P H L a n d H L t he el e v ati o n i n tra nsa mi nases m ust prece d e or be c oi nci d e nt wit h (i.e. o n t he 
sa me da y) t he ele vati o n i n T B L, b ut t here is n o s pecifie d ti mefra me wit hi n w hic h t he ele vati o ns 
i n tra nsa mi nases a n d T B L m ust occ ur. 
3. I de ntific ati o n  of P ote nti al H y’s L a w C ases  
I n or der t o i de ntif y cases of P H L it is i m p orta nt t o perf or m a c o m pre h e nsi ve re vie w of l a b orat or y 
data f or a n y s ubject  w h o meets a n y of t he f oll o wi n g i de ntificati o n criteria i n is olati o n or i n 
c o m bi nati o n:  
•  
A L T ≥ 3 x U L N  

Cli nical St u d y Pr ot oc ol  
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St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
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4 5  (5 2 ) 
 
•  
A S T ≥ 3 x U L N  
•  
T B L ≥ 2 x U L N  
 
W he n a s u bject meets a n y of t he i de ntificati o n crit eria, i n is olati o n or i n c o m bi nati o n, t he ce ntral 
la b orat or y will i m me diatel y se n d a n alert t o t he I n vesti gat or (als o se nt t o Astra Ze neca 
re pres e ntati ve).  
T he I n vesti g at or will als o re mai n vi gila nt f or a n y l ocal la b orat or y re p orts w here t he 
i de ntificati o n criteria are met, w here t his is t he cas e t he I n vesti gat or will: 
•  
N otif y t he  Astra Ze n eca re prese nt ati ve  
•  
Re q uest a re p eat of t he t est ( ne w bl o o d dra w) b y t he ce ntr al la b o rat or y 
•  
C o m plete t he a p pr o priate u nsc he d ule d la b orat or y C R F m o d ule(s) wit h t he ori gi nal l ocal 
la b orat or y test res ult 
W he n t he i de ntificati o n criteria are met fr o m ce ntr al or l ocal la b orat or y res ults t he I n vesti gat or 
will wit h o ut dela y:  
•  
Deter mi ne w h et her t he  s u bject meets P H L criteria (see  S ecti o n 2 Defi niti o ns wit hi n  t his 
A p pe n di x f or defi niti o n) b y re vie wi n g la b orat or y re p orts fr o m all pre vi o us visits 
(i ncl u din g b ot h ce ntral a n d l ocal la b orat or y res ults)  
T he I n vesti gat or will wit h o ut dela y re vie w eac h n e w l a b orat or y re p ort a n d if t he i de ntificati o n 
criteria are met will:  
•  
N otif y t he Astra Ze n eca re prese nt ati ve  
•  
Deter mi ne w h et her t he s u bject meets P H L criteria ( see S ecti o n 2 Defi niti o ns wit hi n t his 
A p pe n di x f or defi niti o n ) b y re vie wi n g la b orat or y re p orts fr o m all pre vi o us visits 
•  
Pr o m ptl y e nter t he la b orat or y data i nt o t he la b orat or y C R F  
4 . F oll o w -u p  
4. 1  P ote nti al H y’s L a w Criteri a n ot met  
If t he s u bject d oes n ot m ee t P H L criteri a t he I n v esti gat or will: 
•  
I nf or m t he Astr a Ze neca re prese nt ati ve t hat t he s u bject has n o t met P H L crit eria. 
•  
Perf or m f oll o w -u p o n s u bse q ue nt la b orat or y res ults acc or di n g t o t he g ui da nce pr o vi de d i n 
t he Cli nical St u d y Pr ot oc ol. 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
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4 6  (5 2 ) 
 
4. 2  P ote nti al H y’s L a w Criteri a m et  
If t he s u bject d oes m eet P H L criteria t he I n vesti gat or will: 
•  
Deter mi ne w h et her P H L  criteria were m et at a n y st u d y visit pri or t o starti n g st u d y 
treat me nt ( See S ecti o n 6. Acti o ns  Re q uire d W he n P ote ntial H y’s La w Criteria are Met 
Bef ore a n d After Starti n g St u d y Treat m e nt) 
•  
N otif y t he Astra Ze n eca re prese nt ati ve w h o will t he n i nf or m t he ce ntral St u d y Tea m  
T he St u d y P h ysicia n c o ntacts t he I n vesti gat or, t o pr o vi de g ui da nce, dis c uss a n d a gree a n 
a p pr oac h f or t he st u d y s u bjects’ f oll o w-u p a n d t h e c o nti n u o us re vie w of data.  S u bse q ue nt t o t his 
c o ntact t he I n v esti gat or will: 
•  
M o nit or t he s u bject u ntil li ver bi oc he mistr y para meters a n d  a p pr o priat e cli nical 
s y m pt o ms a n d si g ns ret ur n t o n or mal or baseli ne l e vels, or as l o n g as me di call y i n dicate d  
•  
I n v esti gate t he eti ol o g y of t he e ve nt a n d perf or m dia g n ostic i n vesti gati o ns as disc usse d 
wit h t he St u d y P h ysicia n. F or st u dies usi n g a ce ntr al la b orat or y a d d: T his i ncl u des 
deci di n g w hic h t he tests a vaila ble i n t he H y’s l a w la b kit s h o ul d be use d  
•  
C o m plete t he t hree Li ver C R F M o d ules as i nf or m ati o n bec o mes a v aila ble  
•  
If at a n y ti me (i n c o ns ult ati o n wit h t he St u d y P h ysicia n) t he P H L cas e meets seri o us 
criteria, re p ort it as a n S A E usi n g sta n dar d re p orti n g pr oce d ures . 
5. Re vie w  a n d Assess m e nt of P ote nti al H y’s L a w C ases  
T he i nstr ucti o ns i n t his Secti o n s h o ul d be f oll o we d f or all cas es w here P H L criteria are met.  
N o later t ha n 3 wee ks after t he bi oc he mistr y a b n or malit y was i nitiall y detecte d, t he St u d y 
P h ysicia n  c o ntacts t he I n vesti gat or i n or der t o re vie w a vaila bl e data a n d a gree o n w het h er t here 
is a n alter nati ve e x pla natio n f or meeti n g P H L crit eria ot her t h a n DI LI ca us e d b y t he I M P.  T he 
Astra Ze neca  Gl o b al Cli nical Lea d or e q ui vale nt  a n d Gl o bal Safet y P h ysicia n will als o be 
i n v ol ve d i n t his re vie w t o get her wit h ot her s u bject matter e x perts as a p pr o priate.   
Acc or di n g t o t h e o utc o m e of t he re vie w a n d assess me nt, t he I n v esti gat or will f oll o w t he 
i nstr ucti o ns bel o w. 
If t here is a n a gree d alter nati ve e x pla nati o n f or t he A L T or A S T a n d T B L  ele vati o ns, a 
deter mi nati o n of w het h er t he alter nati ve e x pla nati o n is a n A E will be ma de a n d s u bse q ue ntl y 
w het her t he A E meets t h e criteri a f or a S A E:  
•  
If t he alter nati ve e x pla n ati o n is n ot  a n A E, rec or d t he alter nati ve e x pla nati o n o n t he 
a p pr o priate C R F  

Cli nical St u d y Pr ot oc ol  
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St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
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4 7  (5 2 ) 
 
•  
If t he alter nati ve e x pla n ati o n is a n A E/ S A E, rec or d t he A E / S A E i n t he C R F acc or di n gl y 
a n d foll o w t he A Z sta n dar d pr ocess es  
If it is a gree d t h at t here is n o e x pla nati o n t hat w o ul d e x plai n t he A L T or A S T a n d T B L 
ele vati o ns ot her t ha n t he I M P:  
•  
Re p ort a n S A E (re p ort ter m ‘ H y’s La w’) acc or di n g t o Astra Ze neca sta n d ar d pr ocesses.  
− 
T he ‘ Me dic all y I m p ort a nt’ seri o us criteri o n s h o ul d be  use d if n o ot her s eri o us 
criteria a p pl y  
− 
As t here is n o alter nati ve e x pla nati o n f or t he H L case, a ca usalit y assess me nt of 
‘relate d’ s h o ul d be assi g ne d. 
If, t here is a n u na v oi da bl e dela y, of o v er 3 wee ks, i n o btai ni n g t he i nf or mati o n necessar y t o 
assess w het her or n ot t he case me ets t he criteri a f or H L, t he n it is ass u me d t hat t here is n o 
alter nati ve e x pl a nati o n u ntil s uc h ti me as a n i nf or me d decisi o n ca n b e ma de:  
•  
Re p ort a n S A E (re p ort ter m ‘ P ote ntial H y’s La w’) a p pl yi n g seri o us criteria a n d ca usalit y 
assess me nt as per a b o ve 
•  
C o nti n ue f oll o w -u p a n d re vie w acc or di n g t o a gree d pla n.  O nce t he necessar y 
s u p ple me ntar y i nf or mati o n is o btai ne d, re peat t he re vie w a n d assess me nt t o deter mi ne 
w het her H L criteri a are met.  U p date t he S A E  re p ort acc or di n g t o t he o utc o me of t he 
re vie w a m e n di n g t he re p orte d ter m if a n alter nati v e e x pla nati o n f or t he li ver bi oc he mistr y 
ele vati o ns is deter mi ne d.  
6. Acti o ns  Re q uire d W he n P ote nti al H y’s L a w Criteri a a re Met Bef ore a n d After St arti n g 
St u d y Tre at m e nt  
T his secti o n is a p plica ble t o s u bjects  wit h li ver metastases w h o meet P H L criteria o n st u d y 
treat me nt ha vi n g pre vi o usl y met P H L criteria at a st u d y visit pri or t o starti n g st u d y treat me nt. 
At t he first o n st u d y treat me nt occ urre nce of  P H L criteria b e i n g met t he I n v esti gat or will: 
•  
D eter mi ne if t here has b ee n a si g nifica nt c ha n ge i n t he s u bjects’ c o n diti o n # c o m pare d 
wit h t he last visit w here P H L criteria were m et #  
− 
If t here is n o si g nifica nt c ha n ge n o acti o n is re q uire d 
− 
If t here is a si g nifica nt c ha n ge n otif y t he Astra Ze n eca re prese nt ati ve, w h o will 
i nf or m t he ce ntr al St u d y Tea m, t he n f oll o w t he s u bse q ue nt pr ocess descri b e d in 
4. 2  P ote ntial H y’s La w Criteria met  of t his A p pe n di x  
# A ‘si g nifica nt’ c ha n ge i n t he s ubject ’s c o n diti o n refers t o a cli nicall y rele va nt c ha n ge i n a n y of 
t he i n di vi d ual li ver bi oc he mistr y para meters ( A L T, A S T or t otal bilir u bi n) i n is olati o n or i n 
c o m bi nati o n, or a cli nicall y rele va nt c ha n ge i n ass ociate d s y m pt o ms.  T he deter mi nati o n of 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
 
 
 
4 8  (5 2 ) 
 
w het her t here has b ee n a si g nifica nt c ha n ge will be at t he discreti o n of t he I n vesti gat or, t his ma y 
be i n c o ns ultati o n wit h t he St u d y P h ysicia n if t here is a n y u ncertai nt y.  
7. Acti o ns  Re q uire d f or Re pe at E pis o des of P ote nti al H y’s L a w  
T his secti o n is a p plica bl e w he n a s u bject meets P H L criteria o n st u d y tr eat me nt a n d has alr ea d y 
met P H L criteria at a pre vi o us o n st u d y treat me nt visit.  
T he re q uir e me nt t o c o n d uct f oll o w -u p, re vie w a n d assess me nt of a re peat occ urre nce(s) of P H L 
is base d o n t he nat ure of t he alternati ve ca use i de ntifie d f or t he pre vi o us occ urre n ce.   
T he i n vesti gat or s h o ul d deter mi ne t he ca use f or t h e pre vi o us occ urre nce of P H L criteria bei n g 
met a n d a ns wer t he f oll o wi n g q uesti o n:  
•  
Was t he alter nati ve ca use f or t he pre vi o us o cc urre nce of P H L criteri a b ei n g met f o u n d t o 
be t he disease u n d er st u d y e. g. c hr o nic or pr o gressi n g mali g na nt disease, se vere i nf ecti o n 
or li ver disease,  or di d t he s u bject meet P H L criteria pri or t o starti n g st u d y treat me nt a n d 
at t heir first o n st u d y treat me nt visit as descri b e d i n secti o n 6. Acti o ns  Re q uire d W he n 
P ote ntial H y’s La w Criteria are Met Bef ore a n d After Starti n g St u d y Treat m e nt  
If N o: f oll o w t he pr ocess descri be d i n 4. 2  P ote ntial H y’s La w Criteria m et  of t his A p pe n di x  
If Yes: 
Deter mi ne if t here has b ee n a si g nifica nt c ha n ge i n t he s u bject’s c o n diti o n# c o m pare d wit h w h e n 
P H L criteria w ere pre vi o usl y met  
•  
If t here is n o si g nifica nt c ha n ge n o acti o n is re q uire d 
•  
If t here is a si g nifica nt c h a n ge f oll o w t he pr ocess d escri be d i n Secti o n 4. 2 of t his 
A p pe n di x  
# A ‘si g nifica nt’ c ha n ge i n t he s u bject’s c o n diti o n refers t o a cli nicall y rele va nt c ha n ge i n a n y of 
t he i n di vi d ual li ver bi oc he mistr y para meters ( A L T, A S T or t otal bilir u bi n) i n is olati on or i n 
c o m bi nati o n, or a cli nicall y rele va nt c ha n ge i n ass ociate d s y m pt o ms.  T he deter mi nati o n of 
w het her t here has b ee n a si g nifica nt c ha n ge will be at t he discreti o n of t he I n vesti gat or; t his ma y 
be i n c o ns ultati o n wit h t he St u d y P h ysici a n if t here is a n y u ncertai nt y.  
 
 
 
 
 

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
 
 
 
4 9  (5 2 ) 
 
 
1 2    SI G N A T U R E S  
A S T R A Z E N E C A SI G N A T U R E( S)  
 
A pr os pecti ve, m ultice nter, p h ase -I V st u d y t o assess the s afet y of fi xe d d ose c o m bi n ati o n 
of d a p a glifl ozi n a n d s a x a gli pti n i n I n di a n T y pe 2 Di a betes Mellit us ( T 2 D) p atie nts.  
  
 
 
T his St u d y Pr ot oc ol h as bee n s u bjecte d t o a n i nter n al Astr a Ze nec a revie w  
 
I a gree t o t he ter ms of t his St u d y pr ot oc ol.  
 
Astr a Ze nec a re prese nt ati ve  
 
 
 
 
 
 
 
 
T his d oc u me nt c o ntai ns c o nfi de ntial i nf or mati o n, w hic h s h o ul d n ot be c o pie d, referre d 
t o, release d or p u blis he d wit h o ut writte n a p pr o val fr o m Astra Ze neca. I n vesti gat ors are 
ca uti o ne d t hat t he i nf or m ati o n i n t his pr ot oc ol ma y be s u bject t o c ha n g e a n d re visi o n.  
 
 
 
 
 
 
 
 
P P D

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
 
 
 
5 0  (5 2 ) 
 
SI G N A T U R E S  
 
 
 
A S T R A Z E N E C A SI G N A T U R E( S)  
  
 
 
 
A pr os pecti ve, m ultice nter, p h ase -I V st u d y t o assess t he s afet y of fi xe d d ose c o m bi n ati o n 
of d a p a glifl ozi n a n d s a x a gli pti n i n I n di a n T y pe 2 Di a betes Mellit us ( T 2 D) p atie nts.  
  
 
 
T his St u dy Pr ot oc ol h as bee n s u bjecte d t o a n i nter n al Astr a Ze nec a revie w  
 
I a gree t o t he ter ms of t his St u d y pr ot oc ol.  
 
Astr a Ze nec a re prese nt ati ve  
 
 
 
 
 
 
 
 
 
 
T his d oc u me nt c o ntai ns c o nfi de ntial i nf or mati o n, w hic h s h o ul d n ot be c o pie d, referre d 
t o, release d or p u blis he d wit h o ut writte n a p pr o val fr o m Astra Ze neca. I n vesti gat ors are 
ca uti o ne d t hat t he i nf or m ati o n i n t his pr ot oc ol ma y be s u bject t o c ha n g e a n d re visi o n.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
P P D

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
 
 
 
5 1  (5 2 ) 
 
SI G N A T U R E S  
 
 
 
A S T R A Z E N E C A SI G N A T U R E( S)  
  
 
 
 
A pr os pecti ve, m ultice nter, p h ase -I V st u d y t o assess t he s afet y of fi xe d d ose c o m bi n ati o n 
of d a p a glifl ozi n a n d s a x a gli pti n i n I n di a n T y pe 2 Di a betes Mellit us ( T 2 D) p atie nts.  
  
 
 
T his St u dy Pr ot oc ol h as bee n s u bjecte d t o a n i nter n al Astr a Ze nec a rev ie w 
 
I a gree t o t he ter ms of t his St u d y pr ot oc ol. 
 
Astr a Ze nec a re prese nt ati ve  
 
 
 
 
 
 
 
 
 
 
T his d oc u me nt c o ntai ns c o nfi de ntial i nf or mati o n, w hic h s h o ul d n ot be c o pie d, referre d 
t o, release d or p u blis he d wit h o ut writte n a p pr o val fr o m Astra Ze neca. I n vesti gat ors are 
ca uti o ne d t hat t he i nf or m ati o n i n t his pr ot oc ol ma y be s u bject t o c ha n g e a n d re visi o n.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
P P D

Cli nical St u d y Pr ot oc ol  
Dr u g S u bsta nce Da pa glifl ozi n + Sa xa gli pti n   
St u d y C o de D 1 6 8 3 C 0 0 0 1 3  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
 
 
 
5 2  (5 2 ) 
 
 
 
 
 
 
SI G N A T U R E S  
 
 
 
A S T R A Z E N E C A SI G N A T U R E( S)  
  
 
 
 
A pr os pecti ve, m ultice nter, p h ase -I V st u d y t o assess t he s afet y of fi xe d d ose c o m bi n ati o n 
of d a p a glifl ozi n a n d s a x a gli pti n i n I n di a n T y pe 2  Di a betes Mellit us ( T 2 D) p atie nts.  
  
 
 
T his St u dy Pr ot oc ol h as bee n s u bjecte d t o a n i nter n al Astr a Ze nec a revie w  
 
I a gree t o t he ter ms of t his St u d y pr ot oc ol. 
 
Astr a Ze nec a re prese nt ati ve 
 
 
 
 
 
 
 
 
 
 
 
 
T his d oc u me nt c o ntai ns c o nfi de ntial i nf or mati o n, w hic h s h o ul d n ot be c o pie d, referre d 
t o, release d or p u blis he d wit h o ut writte n a p pr o val fr o m Astra Ze neca. I n vesti gat ors are 
ca uti o ne d t hat t he i nf or m ati o n i n t his pr ot oc ol ma y be s u bject t o c ha n g e a n d re visi o n. 
 
 
 
 
 
 
P P D