Clinical trial NCT04445714
Conditions: Type 2 Diabetes Mellitus
Sponsor: AstraZeneca
Start date: 2021-04-07; Completion date: 2023-03-14
Enrollment: 196 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
During the study, an AstraZeneca representative/delegate will have regular contacts with the study site, including visits to site for the site monitoring and source data verification activities. Electronic Case Report Forms (eCRF) will be used for data collection and query handling. The investigator will sign the completed electronic Case Report Forms. A copy of the completed electronic Case Report Forms will be archived at the study site. Authorized representatives of AstraZeneca or delegate, a regulatory authority, or an Ethics Committee may perform audits or inspections at the center's. Number and percentages of Incidence of adverse events will be presented, stratified by age/gender/baseline medications. Annualised event rate shall also be presented in addition to the incidence rate during the study. Mean change in HbA1C from baseline to 6 months for patients will be analysed using paired t test / Wilcoxon signed-rank test at 5% level of significance.

Arms: arm 1: Singe arm once daily fixed dose combination of Dapa/Saxa 10 mg/5 mg administered orally
Interventions: intervention 1: dapagliflozin and saxagliptin
Intervention descriptions: intervention 1: Combination of dapagliflozin and saxagliptin tablet once daily fixed dose combination of Dapa/Saxa 10 mg/5 mg administered orally

Protocol documents:
Prot_000.pdf: 
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  
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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   
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 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  
Date 2 2 Se pte m ber 2 0 2 0  
 
 
 
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  
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  (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  
Versi o n 3. 0  
Date 2 2 Se pte m ber 2 0 2 0  
 
 
 
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  
Dr u g S u bsta nce Da pa glifl oz i 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 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

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