A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin Added to Metformin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Sponsor: Lexicon Pharmaceuticals

Offi ci al Titl e:  A  R a n d o miz e d,  D o u bl e -bli n d,  Pl a c e b o -c o ntr oll e d,  P ar all el -gr o u p, 
M ulti c e nt er St u d y  t o E v al u at e t h e Effi c a c y a n d S af et y of S ot a glifl ozi n 
A d d e d t o M etf or mi n i n P ati e nts  wit h T y p e 2 Di a b et es M ellit us W h o H a v e 
I n a d e q u at e Gl y c e mi c C o ntr ol o n M etf or mi n  
N C T N u m b er:  N C T 0 2 9 2 6 9 5 0  
D o c u m e nt  D at e : Pr ot o c ol  V er si o n 2:  2 1- De c e m b er - 20 1 7 

 
 
A ny a n d all i nf or m ati o n pres e nt e d i n t his d oc u m e nt s h all b e tre at e d as c o nfi d e nti al a n d s h all r e m ai n t h e excl usiv e pr o p erty of S a n ofi ( or a ny of its 
affili at e d c o m p a ni es). T h e us e of s uc h c o nfi d e nti al i nf or m ati o n m ust b e r e strict e d t o t h e reci pi e nt f or t h e a gre e d p urp os e a n d m ust n ot b e 
discl os e d, p u blis h e d or ot h er wis e c o m m u nic at e d t o a ny u n a ut h oriz e d p ers o ns, f or a ny r e as o n, i n a ny f or m w h ats o ev er wit h o ut t h e pri or writt e n 
c o ns e nt of S a n ofi (or t h e c o nc ern e d affili at e d c o m p a ny); ‘ affili ate d c o m p a ny’ m e a ns a ny c orp orati o n, p art n ers hi p or ot h er e ntit y w hic h at t h e d at e 
of c o m m u nic ati o n or aft er w ar ds (i) c o ntr ols dir ectly or i n dir ectly S a n ofi, (ii) is dir ectly or i n dir ectly c o ntr oll e d by S a n ofi,  wit h ‘c o ntr ol’ m e a ni n g 
dir ect or i n dir ect o w n ers hi p of m or e t h a n 5 0 % of t h e c a pit al st ock or t h e v oti n g ri g hts i n s uc h c or p or ati o n, p art n ers hi p or ot h er e ntity 
 
 
P a g e 1  
 
A M E N D E D C LI NI C A L T RI A L P R O T O C O L N O. 0 2 
 
C O M P O U N D: s ot a glifl o zi n/ S A R 4 3 9 9 5 4 
A R a n d o mi z e d, D o u bl e- bli n d, Pl a c e b o- c o ntr o ll e d, P ar all el- gr o u p, M ulti c e nt er St u d y 
t o E v al u at e t h e Effi c a c y a n d S af et y of S ot a glifl o zi n A d d e d t o M etf or mi n i n P ati e nt s 
wit h T y p e 2 Di a b et e s M ellit u s W h o H a v e I n a d e q u at e Gl y c e mi c C o ntr ol o n 
M etf or mi n 
S T U D Y N U M B E R: E F C 1 4 8 3 4 
S T U D Y N A M E: S O T A- M E T ( S O T A glif l o zi n a d d e d t o M E Tf or mi n) 
V E R SI O N D A T E / S T A T U S: A p pr o v al d at e ( 1 9- D e c- 2 0 1 7) / A p pr o v e d 
Pr ot o c ol A m e n d m e nt 0 2 
V er si o n n u m b er: 1 ( el e ctr o ni c 1. 0)  
D at e : 1 9- D e c- 2 0 1 7 
A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 1  
V er si o n n u m b er: 1 ( el e ctr o ni c 1. 0)  
D at e : 2 4- A pr- 2 0 1 7 
Pr ot o c ol A m e n d m e nt 0 1 
V er si o n n u m b er: 1 ( el e ctr o ni c 1. 0)  
D at e : 2 4- A pr- 2 0 1 7 
Cli ni c al Tri al Pr ot o c ol 
V er si o n n u m b er: 1 ( el e ctr o ni c 1. 0)  
D at e : 2 7- J ul- 2 0 1 6 
E u dr a C T  
2 0 1 6- 0 0 1 8 0 0- 4 9 
I N D N u m b er( s) 
 
V er si o n N u m b er:  
1  
W H O u ni v er s al tri al n u m b er:  
U 1 1 1 1- 1 1 8 1- 6 1 4 5 
D at e: 
1 9- D e c- 2 0 1 7  
T ot al n u m b er of p a g e s:  
1 2 7 
 
 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 2 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 2 
N A M E S A N D A D D R E S S E S O F 
C O O R DI N A TI N G 
I N V E S TI G A T O R 
 
N a m e: 
A d dr e s s: 
 
 
T el: 
F a x: 
E- m ail: 
 
 
M O NI T O RI N G T E A M’ S 
R E P R E S E N T A TI V E 
 
N a m e: 
A d dr e s s: 
 
 
 
T el: 
F a x: 
E- m ail: 
 
 
S P O N S O R 
 
C o m p a n y: 
A d dr e s s: 
 
 
 
 
 
 
O T H E R E M E R G E N C Y 
T E L E P H O N E N U M B E R S 
 
 
 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 3 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 3 
C LI NI C A L T RI A L S U M M A R Y 
 
C O M P O U N D: s ot a g lifl o zi n/ S A R 4 3 9 9 5 4 
S T U D Y N o.: E F C 1 4 8 3 4 
TI T L E 
A R a n d o miz e d, D o u bl e- bli n d, Pl ac e b o-c o ntr oll e d, Par all el- gr o u p, 
M ultic e nt er St u dy t o Ev al u at e t h e Effic acy a n d Saf ety of Sot a glifl ozi n 
A d d e d t o M etf or mi n i n P ati e nts wit h Ty p e 2 Di a b et es M ellit us W h o 
H av e I n a d e q u at e Glyc e mic C o ntr ol o n M etf or mi n 
I N V E S TI G A T O R/ T RI A L L O C A TI O N 
M ulti n ati o n al 
P H A S E O F D E V E L O P M E N T 
3 
S T U D Y O B J E C TI V E S 
 
Pri m ar y o bj e cti v e: 
T h e pri m ary o bj ectiv e of t his st u d y is t o d e m o nstr at e t h e s u p eri ority 
of s ot a glifl ozi n 4 0 0 m g v ers us pl ac e b o o n h e m o gl o bi n A1c ( H b A 1c) 
r e d ucti o n at W e ek 2 6 i n p ati e nts with ty p e 2 di a b et es m ellit us ( T 2 D) 
w h o h av e i n a d e q u at e glyc e mic c o ntr ol wit h m etf or mi n.  
S e c o n d ar y o bj e cti v e s: 
•  
T o c o m p ar e s ot a glifl ozi n 4 0 0 m g v ers us pl ac e b o f or:  
- 
C h a n g e fr o m Bas eli n e i n 2- h o ur p ost pr a n di al gl uc os e 
( P P G) f oll o wi n g a mix e d m e al at W e ek 2 6 
- 
C h a n g e fr o m Bas eli n e i n f asti n g pl as m a gl uc os e 
( F P G) at W e ek 2 6 
- 
C h a n g e fr o m Bas eli n e i n b o dy w ei g ht at W e ek 2 6 
- 
C h a n g e fr o m Bas eli n e i n syst olic bl o o d pr ess ur e 
( S B P) at W e ek 1 2 f or p ati e nts wit h B as eli n e S B P 
≥1 3 0 m m H g  
- 
C h a n g e fr o m Bas eli n e i n S B P at W e ek 1 2 f or all 
p ati e nts 
- 
Pr o p orti o n of p ati e nts wit h H b A1c < 6. 5 %, < 7. 0 % at 
W e ek 2 6 
•  
T o ev al u at e t h e s af ety of s ot a glifl ozi n 4 0 0 m g v ers us 
pl ac e b o t hr o u g h o ut t h e 7 9- w e ek tri al 
Ot h er: 
•  
T o c o m p ar e s ot a glifl ozi n v ers us pl ac e b o wit h r es p ect t o 
c h a n g e fr o m Bas eli n e i n t h e f oll o wi n g e n d p oi nts: 
- 
Uri n e al b u mi n-cr e ati ni n e r ati o ( A C R) 
- 
Uri n ary gl uc os e excr eti o n ( U G E) a n d uri n e 
gl uc os e-cr e ati ni n e r ati o ( G C R) 
- 
Esti m at e d gl o m er ul ar filtr ati o n r at e ( e G F R) 
- 
R e d ucti o n i n b o dy w ei g ht by ≥2 %, ≥5 %, a n d ≥1 0 % 
•  
T o c o m p ar e s ot a glifl ozi n v ers us pl ac e b o f or: 
- 
C h a n g e fr o m Bas eli n e i n H b A1c at W e ek 7 9 
- 
C h a n g e fr o m Bas eli n e i n F P G at W e ek 7 9 
- 
C h a n g e fr o m Bas eli n e i n S B P at W e ek 2 6 f or all 
p ati e nts a n d f or p ati e nts wit h Bas eli n e S B P 
≥1 3 0 m m H g 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 4 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 4 
- 
C h a n g e fr o m Bas eli n e i n S B P at W e ek 7 9 f or all 
p ati e nts a n d f or p ati e nts wit h Bas eli n e S B P 
≥1 3 0 m m H g 
- 
C h a n g e fr o m Bas eli n e i n b o dy w ei g ht at W e ek 7 9 
•  
T o c o m p ar e t h e us e of r esc u e m e dic ati o ns f or 
hy p er glyc e mi a i n t h e s ot a glifl ozi n a n d pl ac e b o tr e at m e nt 
gr o u ps 
•  
T o ass ess pl as m a c o nc e ntr ati o ns of s ot a glifl ozi n a n d its 
3- O- gl uc ur o ni d e m et a b olit e 
A m b ul at ory Bl o o d Pre s s ure M o ni t ori n g ( A B P M) s u b st u d y 
A s u bst u dy will b e u n d ert ak e n t o m o nit or a m b ul at ory bl o o d pr ess ur e 
(i n a d diti o n t o all ot h er st u dy ass ess m e nts) i n a s u bs et of t h e t ot al 
st u dy p o p ul ati o n w h o h av e m e a n S B P ≥1 3 0 m m H g at Scr e e ni n g. 
T h e pri m ary o bj ectiv e of t h e s u bst u dy is t o c o m p ar e t h e eff ect of 
s ot a glifl ozi n v ers us pl ac e b o i n a s u bs et of p ati e nts wit h m e a n S B P 
≥1 3 0 m m H g at Scr e e ni n g o n 2 4- h o ur  av er a g e S B P at W e ek 1 2. 
T h e s ec o n d ary o bj ectiv es of t h e A B P M s u bst u dy ar e t o c o m p ar e t h e 
eff ect of s ot a glifl ozi n v ers us pl ac e b o i n a s u bs et of p ati e nts wit h 
m e a n S B P ≥1 3 0 m m H g at Scr e e ni n g o n t h e f oll o wi n g: 
•  
2 4- h o ur av er a g e S B P at W e ek 2 6  
•  
2 4- h o ur av er a g e di ast olic bl o o d pr ess ur e ( D B P) at 
W e eks 1 2 a n d 2 6 
•  
Av er a g e a dj ust e d a w ak e ti m e bl o o d pr ess ur e ( B P) as 
m e as ur e d by S B P a n d D B P at W e eks 1 2 a n d 2 6 wit h 
a dj ust m e nt b as e d o n acti gr a p hy  
•  
Av er a g e a dj ust e d sl e e pi n g ti m e B P as m e as ur e d by S B P 
a n d D B P at W e eks 1 2 a n d 2 6 wit h a dj ust m e nt b as e d o n 
acti gr a p hy  
S T U D Y D E SI G N 
T his is a Ph as e 3, m ultic e nt er, r a n d o miz e d, d o u bl e- bli n d, 
pl ac e b o-c o ntr oll e d, p ar all el- gr o u p st u dy t h at is a ntici p at e d t o e nr oll 
a p pr oxi m at ely 5 0 0 p ati e nts. 
Pati e nts t aki n g m etf or mi n at a st a bl e d os a g e ≥1 5 0 0 m g/ d ay f or at 
l e ast 1 2 w e eks b ef or e e nr oll m e nt will b e eli gi bl e f or scr e e ni n g. 
Pati e nts o n m etf or mi n at a d os e < 1 5 0 0 m g/ d ay at t h e ti m e of 
e nr oll m e nt (st a bl e d os e f or at l e ast 1 2 w e eks b ef or e e nr oll m e nt) m ay 
b e eli gi bl e f or scr e e ni n g if d oc u m e nt ati o n of l ack of t ol er a nc e of a 
m etf or mi n d os e ≥1 5 0 0 m g/ d ay c a n b e pr ovi d e d.  
All p ati e nts will h av e a Scr e e ni n g P e ri o d c o nsisti n g of a Scr e e ni n g 
p h as e of u p t o 2 w e eks a n d a 2- w e ek si n gl e- bli n d R u n-i n p h as e pri or 
t o r a n d o miz ati o n. I n or d er t o q u alify f or r a n d o miz ati o n, p ati e nts m ust 
d e m o nstr at e c o m pli a nc e b as e d u p o n t a bl et c o u nt ( ≥8 0 %) d uri n g t h e 
R u n-i n p h as e. 
R a n d o miz ati o n will b e str atifi e d by:  
•  
H b A1c at Scr e e ni n g ( ≤8. 0 %, > 8. 0 %) 
•  
S B P at Scr e e ni n g ( < 1 3 0 m m H g, ≥1 3 0 m m H g)  
F oll o wi n g r a n d o miz ati o n, p ati e nts will h av e a 2 6- w e ek, d o u bl e- bli n d 
C or e Tr e at m e nt Peri o d, a 5 3- w e ek d o u bl e- bli n d ext e nsi o n, a n d a 
4- w e ek p ost-tr e at m e nt F oll o w- u p visit t o c oll ect s af ety i nf or m ati o n. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 5 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 5 
All p ati e nts will h av e P P G ass ess e d f oll o wi n g a M M T T at W e eks 0, 
2 6, a n d 7 9. 
A t ot al of 5 0 0 p ati e nts ≥1 8 y e ars of a g e will b e r a n d o mly assi g n e d 
1: 1 t o 1 of t h e f oll o wi n g 2 tr e at m e nt gr o u ps: 
•  
Sot a glifl ozi n 4 0 0 m g as t w o 2 0 0 m g t a bl ets, o nc e d aily  
•  
Pl ac e b o as t w o pl ac e b o t a bl ets (i d e ntic al t o s ot a glifl ozi n i n 
a p p e ar a nc e), o nc e d aily 
H e m o gl o bi n A 1c, F P G, a n d P P G (fr o m M M T T ass ess m e nt) will b e 
m ask e d t o st u dy sit es a n d p ati e nts aft er r a n d o miz ati o n u ntil st u dy 
e n d. T o pr ev e nt p arti al u n bli n di n g, U G E a n d uri n e G C R r es ults will 
b e m ask e d t o st u dy sit es a n d p ati e nts. Ad diti o n ally, uri n alysis by 
di pstick will n ot i ncl u d e t h e m e as ur e m e nt of uri n e gl uc os e. Uri n e 
gl uc os e, al b u mi n, c alci u m a n d cr e ati ni n e will b e m e as ur e d 
s e p ar at ely at all o n-sit e visits by t h e c e ntr al l a b or at ory. 
A m b ul at or y Bl o o d Pr e s s ur e M o nit ori n g s u b st u d y: 
Ap pr oxi m at ely 2 0 0 of t h e 5 0 0 e nr oll e d p ati e nts w h o h av e a m e a n 
Scr e e ni n g S B P ≥1 3 0 m m H g ar e ex p ect e d t o p artici p at e i n a n A B P M 
s u bst u dy. A m b ul at ory bl o o d pr ess ur e will b e ass ess e d f or 2 4 h o urs 
d uri n g t h e R u n-i n p h as e, W e ek  1 2, a n d W e ek 2 6. F or e ac h 
ass ess m e nt, t h e p ati e nts p artici p ati n g i n t h e s u bst u dy will att e n d a 
s p eci al s u bst u dy Visit pri or t o t h e sc h e d ul e d visit ( 1 w e ek pri or t o 
R a n d o miz ati o n, a n d 1 d ay pri or t o W e ek 1 2 a n d W e ek 2 6 visits) t o 
h av e t h e A B P M d evic e a p pli e d, as i n dic at e d i n t h e St u dy Fl o w C h art. 
T h e p ati e nts will r et ur n t h e f oll o wi n g d ay f or t h e r e g ul arly sc h e d ul e d 
st u dy visit. 
E arl y t er mi n ati o n: 
If a p ati e nt disc o nti n u es tr e at m e nt wit h i nv esti g ati o n al m e dici n al 
pr o d uct (I M P) e arly d uri n g t h e 2 6- w e ek C or e Tr e at m e nt Peri o d, t h e 
p ati e nt will h av e a Pr e m at ur e E n d- of- Tr e at m e nt ( E O T) Visit a n d a 
F oll o w- u p Visit 4 w e eks aft er t h e l ast d os e of I M P. I n a d diti o n, ev ery 
eff ort will b e m a d e t o h av e all p ati e nts r et ur n t o t h e sit e at t h e ti m e 
c orr es p o n di n g t o t h eir sc h e d ul e d visits, p artic ul arly t h e W e ek 2 6 
Visit. 
P ati e nts p artici p ati n g i n t h e A B P M s u bst u dy will n ot b e r e q uir e d t o 
disc o nti n u e t h e s u bst u dy i n t h e ev e nt t h at t h ey p er m a n e ntly 
disc o nti n u e tr e at m e nt i n t h e m ai n st u dy. Ev ery eff ort s h o ul d b e m a d e 
t o e ns ur e t h at disc o nti n u e d p ati e nts c o m pl et e t h e A B P M s u bst u dy, if 
t h ey ar e willi n g a n d a bl e t o d o s o. 
If a p ati e nt c o m pl et es t h e C or e Tr e at m e nt, b ut disc o nti n u es I M P 
d uri n g t h e ext e nsi o n, t h e p ati e nt will h av e a Pr e m at ur e E O T Visit 
a n d a F oll o w- u p Visit 4 w e eks aft er t h e l ast d os e of I M P. I n a d diti o n, 
ev ery eff ort will b e m a d e t o h av e all p ati e nts r et ur n t o t h e sit e at t h e 
ti m e c orr es p o n di n g t o t h eir q u art erly visits (i e, ev ery 1 3 w e eks) 
d uri n g t h e Ext e nsi o n Peri o d. If a p ati e nt d o es n ot a gr e e t o sit e visits, 
h e/s h e will b e c o nt act e d by t el e p h o n e t o i n q uir e a b o ut t h eir s af ety 
st at us, p artic ul arly at t h e ti m e of sc h e d ul e d W e ek 7 9 Visit. 
D o u bl e- bli n d E xt e n si o n P eri o d: 
P ati e nts still i n t h e st u dy at W e ek 2 6 will c o nti n u e d o u bl e- bli n d 
tr e at m e nt fr o m W e ek 2 7 t o 7 9 i n a 5 3- w e ek d o u bl e- bli n d Ext e nsi o n 
P eri o d. P ati e nts will c o nti n u e t o r ec eiv e t h e bli n d e d m e dic ati o n 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 6 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 6 
(s ot a glifl ozi n or pl ac e b o) t o w hic h t h ey w er e r a n d o miz e d o n D ay 1. 
Pati e nts w h o r ec eiv e d r esc u e m e dic ati o n d uri n g t h e 2 6- w e ek C or e 
Tr e at m e nt P eri o d will c o nti n u e o n t h e s a m e r esc u e m e dic ati o n 
d uri n g t h e d o u bl e- bli n d Ext e nsi o n Peri o d ( u nl ess t h e I nv esti g at or 
c o nsi d ers a c h a n g e n ec ess ary f or s af ety r e as o ns). T h e crit eri a f or 
i niti ati o n of r esc u e fr o m W e eks 2 6 t o 7 9 will b e as i n dic at e d i n t h e 
s ecti o n, “R e s c u e t h er a p y .” O p e n-l a b el r esc u e will r e m ai n at t h e 
discr eti o n of t h e I nv esti g at or.  
T h e st u dy d esi g n is pr es e nt e d gr a p hic ally at t h e e n d of t h e sy n o psis. 
S T U D Y P O P U L A TI O N  
M ai n s el e cti o n crit eri a 
I n cl u si o n crit eri a: 
•  
Pati e nts wit h Ty p e 2 Di a b et es c urr e ntly tr e at e d wit h di et 
a n d ex ercis e a n d o n m etf or mi n at a st a bl e d os e 
≥1 5 0 0 m g/ d ay f or at l e ast 1 2 w e eks. H o w ev er, p ati e nts o n 
m etf or mi n at a d os e < 1 5 0 0 m g/ d ay at t h e ti m e of 
e nr oll m e nt (st a bl e d os e f or at l e ast 1 2 w e eks b ef or e 
e nr oll m e nt) m ay b e eli gi bl e f or scr e e ni n g if d oc u m e nt ati o n 
of l ack of t ol er a nc e of a m etf or mi n d os e ≥1 5 0 0 m g/ d ay c a n 
b e pr ovi d e d 
•  
Si g n e d writt e n i nf or m e d c o ns e nt 
M aj or e x cl u si o n crit eri a: 
•  
Ag e < 1 8 y e ars at t h e Scr e e ni n g visit or <l e g al a g e of 
m aj ority, w hic h ev er is gr e at er 
•  
Ty p e 1 di a b et es m ellit us 
•  
Bo dy M ass I n d ex ( B MI) ≤2 0 or > 4 5 k g/ m 2 at Scr e e ni n g 
•  
H b A1c < 7 % or H b A1c > 1 0 % vi a c e ntr al l a b or at ory t est at 
Scr e e ni n g 
•  
F asti n g pl as m a gl uc os e > 1 5 m m ol/ L ( > 2 7 0 m g/ d L) 
m e as ur e d by t h e c e ntr al l a b or at ory at Scr e e ni n g ( Visit 1) 
a n d c o nfir m e d by a r e p e at t est ( > 1 5 m m ol/ L [ > 2 7 0 m g/ d L]) 
b ef or e r a n d o miz ati o n 
•  
W o m e n of c hil d b e ari n g p ot e nti al n ot willi n g t o us e hi g hly 
eff ectiv e m et h o d(s) of birt h c o ntr ol or w h o ar e u n willi n g or 
u n a bl e t o b e t est e d f or pr e g n a ncy (s e e Ap p e n dix A ), 
d uri n g t h e st u dy 
•  
Tr e at e d wit h a n a nti di a b etic p h ar m ac ol o gic al r e gi m e n 
ot h er t h a n m etf or mi n ≥1 5 0 0 m g per d ay ( or m axi m u m 
t ol er at e d d os e) wit hi n t h e 1 2 w e eks pr ec e di n g t h e 
scr e e ni n g visit 
•  
Pr evi o us us e of a ny ty p es of i ns uli n f or > 1 m o nt h ( at a ny 
ti m e, exc e pt f or tr e at m e nt of g est ati o n al di a b et es) 
•  
Hist ory of pri or g astric s ur gic al pr oc e d ur e, i ncl u di n g g astric 
b a n di n g, wit hi n 3 y e ars b ef or e t h e Scr e e ni n g Visit 
•  
Hist ory of di a b etic k et o aci d osis or n o nk et otic hy p er os m ol ar 
c o m a wit hi n 1 2 w e eks pri or t o t h e Scr e e ni n g Visit 
•  
M e a n of 3 s e p ar at e bl o o d pr ess ur e m e as ur e m e nts 
> 1 8 0 m m H g ( S B P) or > 1 0 0 m m H g ( D B P) 
•  
Hist ory of hy p ert e nsiv e e m er g e ncy wit hi n 1 2 w e eks pri or t o 
Scr e e ni n g ( 1 ) 
 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 7 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 7 
•  
Pati e nts wit h s ev er e a n e mi a, s ev er e c ar di ov asc ul ar 
(i ncl u di n g c o n g estiv e h e art f ail ur e N e w York H e art 
Ass oci ati o n [ N Y H A] I V), r es pir at ory, h e p atic, n e ur ol o gic al, 
psyc hi atric, or activ e m ali g n a nt t u m or or ot h er m aj or 
syst e mic dis e as e or p ati e nts wit h s h ort lif e ex p ect a ncy 
m aki n g i m pl e m e nt ati o n of t h e pr ot oc ol or i nt er pr et ati o n of 
t h e st u dy r es ults diffic ult  
•  
As p art at e a mi n otr a nsf er as e a n d/ or al a ni n e 
a mi n otr a nsf er as e: > 3 ti m es t h e u p p er li mit of t h e n or m al 
l a b or at ory r a n g e 
•  
T ot al bilir u bi n: > 1. 5 ti m es t h e u p p er li mit of t h e n or m al 
l a b or at ory r a n g e ( exc e pt i n c as e of Gil b ert’s sy n dr o m e) 
•  
Us e of syst e mic gl uc oc ortic oi ds ( excl u di n g t o pic al or 
o p ht h al mic a p plic ati o n or i n h al e d f or ms) f or m or e t h a n 
1 0 c o ns ec utiv e d ays wit hi n 9 0 d ays pri or t o t h e Scr e e ni n g 
Visit 
•  
Pati e nt w h o h as t ak e n ot h er i nv esti g ati o n al dr u gs or 
pr o hi bit e d t h er a py f or t his st u dy wit hi n 1 2 w e eks or 
5 h alf-liv es fr o m scr e e ni n g or r a n d o miz ati o n, w hic h ev er is 
l o n g er 
•  
Pr e g n a nt (c o nfir m e d by s er u m pr e g n a ncy t est at 
Scr e e ni n g) or br e astf e e di n g w o m e n 
•  
P ati e nt is u n willi n g or u n a bl e t o p erf or m s elf- m o nit ori n g of 
bl o o d gl uc os e ( S M B G), c o m pl et e t h e p ati e nt di ary, or 
c o m ply wit h st u dy visits a n d ot h er st u dy pr oc e d ur es as 
r e q uir e d p er pr ot oc ol 
•  
C o ntr ai n dic ati o n t o m etf or mi n as p er l oc al l a b eli n g  
T ot al e x p e ct e d n u m b er of p ati e nt s 
5 0 0 
S T U D Y T R E A T M E N T S 
 
I n v e sti g ati o n al m e di ci n al pr o d u ct s 
•  
Sot a glifl ozi n 4 0 0 m g a d mi nist er e d as t w o 2 0 0 m g t a bl ets, 
o nc e d aily, b ef or e t h e first m e al of t h e d ay  
•  
Pl ac e b o a d mi nist er e d as t w o pl ac e b o t a bl ets (i d e ntic al t o 
s ot a glifl ozi n 2 0 0 m g t a bl ets i n a p p e ar a nc e), o nc e d aily, 
b ef or e t h e first m e al of t h e d ay  
N o ni n v e sti g ati o n al m e di ci n al pr o d u ct 
 
•  
M etf or mi n t a bl ets a d mi nist er e d as p er Pri nci p al 
I nv esti g at or 
N O T E: O n st u dy visit d ays occ urri n g o n D ay 1 ( Visit 3), W e ek 2 6 
( Visit 9), a n d W e ek 7 9 ( Visit 1 3), I M P a n d m etf or mi n s h o ul d b e 
a d mi nist er e d acc or di n g t o t h e sc h e d ul e o utli n e d i n Ap p e n dix C . 
T h e d os e of m etf or mi n s h o ul d b e st a bl e t hr o u g h o ut t h e st u dy u nl ess 
d o w n-titr ati o n is r e q uir e d f or s af ety r e as o ns. 
 
R e s c u e t h er a p y 
T h e t hr es h ol d v al u es ar e d efi n e d as f oll o ws, d e p e n di n g o n st u dy 
p eri o d: 
•  
F P G > 2 7 0 m g/ d L ( 1 5. 0 m m ol/ L) fr o m R a n d o miz ati o n u p 
t hr o u g h t h e sc h e d ul e d W e ek 8 visit 
 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 8 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 8 
•  
F P G > 2 4 0 m g/ d L ( 1 3. 3 m m ol/ L) aft er t h e W e ek 8 visit u p 
t hr o u g h t h e sc h e d ul e d W e ek 1 2 visit 
•  
F P G > 2 0 0 m g/ d L ( 1 1. 1 m m ol/ L) aft er t h e W e ek 1 2 visit 
t hr o u g h t h e e n d of t h e 2 6- w e ek C or e Tr e at m e nt P eri o d  
•  
F P G > 1 7 0 m g/ d L ( 9. 4 m m ol/ L) or H b A1c ≥8. 0 % aft er t h e 
W e ek 2 6 Visit t hr o u g h t h e e n d of t h e tr e at m e nt p eri o d 
R o uti n e f asti n g S M B G a n d c e ntr al l a b or at ory al erts o n F P G ( a n d 
H b A1c at W e ek 2 6 a n d o n w ar d) ar e s et u p t o e ns ur e t h at glyc e mic 
p ar a m et er r es ults r e m ai n u n d er pr e d efi n e d t hr es h ol ds. 
•  
If o n e f asti n g S M B G v al u e exc e e ds t h e s p ecific glyc e mic 
li mit o n o n e d ay, t h e p ati e nt c h ecks it a g ai n d uri n g t h e t w o 
f oll o wi n g d ays. If all t h e v al u es i n t hr e e c o ns ec utiv e d ays 
exc e e d t h e s p ecific li mit, t h e p ati e nt s h o ul d c o nt act t h e 
I nv esti g at or a n d a c e ntr al l a b or at ory F P G m e as ur e m e nt 
( a n d H b A1c at W e ek 2 6 a n d o n w ar d) b e p erf or m e d as 
s o o n as p ossi bl e, pr ef er a bly wit hi n 7 d ays, t o c o nfir m t h e 
hy p er glyc e mi a.  
•  
U p o n r ec ei pt of a c e ntr al l a b or at ory r esc u e al ert, a c e ntr al 
l a b or at ory r e-t est m ust b e c o m pl et e d a n d c o nfir m e d as 
exc e e di n g t h e t hr es h ol d f or r esc u e b ef or e r esc u e t h er a py 
is i niti at e d. T h e r e-t est c o nfir m ati o n s h o ul d b e p erf or m e d 
as s o o n as p ossi bl e, b ut wit hi n 7 d ays of r ec ei pt, by 
u nsc h e d ul e d visit.  
I n t h e ev e nt t h at a c o nfir m at ory F P G a n d/ or H b A1c exc e e ds t h e 
t hr es h ol d, t h e I nv esti g at or s h o ul d e ns ur e t h at n o r e as o n a bl e 
ex pl a n ati o n exists f or i ns uffici e nt  gl uc os e c o ntr ol a n d i n p artic ul ar 
t h at: 
•  
T h e i ncr e as e d F P G h as b e e n t est e d at a f asti n g st at us (i e, 
n o f o o d i nt ak e f or ≥8 h o urs) 
•  
I nv esti g ati o n al m e dici n al pro d uct is giv e n at t h e pl a n n e d 
d os e 
•  
T h er e is n o i nt erc urr e nt dis e as e, w hic h m ay j e o p ar diz e 
glyc e mic c o ntr ol ( e g, i nf ecti o us dis e as e) 
•  
C o m pli a nc e t o tr e at m e nt is a p pr o pri at e 
•  
C o m pli a nc e t o di et a n d lif estyl e is a p pr o pri at e 
If a ny of t h e a b ov e c a n r e as o n a bly ex pl ai n t h e i ns uffici e nt glyc e mic 
c o ntr ol, t h e I nv esti g at or s h o ul d c o nsi d er n ot i niti ati n g r esc u e 
m e dic ati o n a n d s h o ul d u n d ert ak e a p pr o pri at e acti o n, i e: 
•  
Ass ess pl as m a gl uc os e i n f asti n g c o n diti o n (i e, aft er at 
l e ast 8 h o urs f ast) 
•  
I niti at e a n ev al u ati o n a n d tr e at m e nt of i nt erc urr e nt dis e as e 
(t o b e r e p ort e d i n A E/c o nc o mit a nt m e dic ati o n p arts of t h e 
e- C R F a n d t h e m e dic al r ec or d) 
•  
Str ess t h e a bs ol ut e n e e d t o b e c o m pli a nt wit h tr e at m e nt 
•  
Or g a niz e a s p ecific i nt ervi e w wit h t h e p ati e nt a n d a 
R e gist er e d Di etici a n or ot h er q u alifi e d n utriti o n 
pr of essi o n al t o r ei nf orc e t h e a bs ol ut e n e e d t o b e c o m pli a nt 
wit h di et a n d lif estyl e r ec o m m e n d ati o ns, a n d sc h e d ul e a 
F P G/ H b A 1c ass ess m e nt at t h e n ext visit 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 9 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 9 
If n o n e of t h e a b ov e m e nti o n e d r e as o ns c a n b e f o u n d, or if 
a p pr o pri at e acti o n f ails t o d ecr e as e F P G/ H b A1c u n d er t h e t hr es h ol d 
v al u es, r esc u e m e dic ati o n m ay b e i ntr o d uc e d. 
O p e n-l a b el r esc u e m e dic ati o n(s) t o  tr e at hy p er glyc e mi a will b e at t h e 
discr eti o n of t h e I nv esti g at or a n d i n acc or d a nc e wit h l oc al st a n d ar d 
of c ar e a n d pr escri bi n g pr actic e. Exc e pt f or s o di u m- gl uc os e 
c otr a ns p ort er ty p e 2 ( S G L T 2) i n hi bit ors, a ny a p pr ov e d m e dic ati o n(s) 
i ncl u di n g or al a nti di a b etic dr u gs or i ns uli n c a n b e pr escri b e d t o tr e at 
t h e hy p er glyc e mi a. F or p ati e nts wit h r e n al i m p air m e nt, 
c o ntr ai n dic ati o ns t o a nti hy p er glyc e mic dr u gs s h o ul d b e t ak e n i nt o 
c o nsi d er ati o n. If a p ati e nt re q uir es glyc e mic r esc u e, t h e I M P 
r ec eiv e d d uri n g t h e r a n d o miz e d, d o u bl e- bli n d Tr e at m e nt Peri o d 
s h o ul d c o nti n u e a n d m ust r e m ai n bli n d e d u ntil t h e e n d of t h e st u dy.  
E N D P OI N T S 
 
 
Pri m ar y effi c a c y e n d p oi nt: 
C h a n g e fr o m Bas eli n e t o W e ek 2 6 i n H b A1c 
S e c o n d ar y effi c a c y e n d p oi nt s: 
•  
C h a n g e fr o m Bas eli n e t o W e ek 2 6 i n 2- h o ur P P G f oll o wi n g 
a mix e d m e al ( M M) 
•  
C h a n g e fr o m Bas eli n e t o W e ek 2 6 i n F P G 
•  
C h a n g e fr o m Bas eli n e t o W e ek 2 6 i n b o dy w ei g ht 
•  
C h a n g e fr o m Bas eli n e t o W e ek 1 2 i n S B P f or p ati e nts wit h 
b as eli n e S B P ≥1 3 0 m m H g 
•  
C h a n g e fr o m Bas eli n e t o W e ek 1 2 i n S B P f or all p ati e nts 
•  
Pr o p orti o n of p ati e nts wit h H b A1c < 6. 5 %, < 7. 0 % at 
W e ek 2 6 
Ot h er effi c a c y e n d p oi nt s: 
•  
C h a n g e fr o m Bas eli n e t o W e ek 1 2 i n S B P f or p ati e nts wit h 
Bas eli n e S B P < 1 3 0 m m H g 
•  
Pr o p orti o n of p ati e nts wit h r e d ucti o n i n b o dy w ei g ht by 
≥2 %, ≥5 %, a n d ≥1 0 % fr o m Bas eli n e  
•  
C h a n g e fr o m Bas eli n e t o W e ek 1 2 i n D B P 
•  
Pr o p orti o n of p ati e nts ac hi evi n g S B P < 1 3 0 m m H g f or 
t h os e wit h Bas eli n e S B P ≥1 3 0 m m H g 
•  
Pr o p orti o n of p ati e nts ac hi evi n g D B P < 8 0 m m H g f or t h os e 
wit h Bas eli n e D B P ≥8 0 m m H g 
•  
Pr o p orti o n of p ati e nts r e q uiri n g r esc u e f or hy p er glyc e mi a 
•  
C h a n g e fr o m Bas eli n e i n: 
- 
Ser u m cr e ati ni n e 
- 
Uri n e A C R 
- 
U G E, a n d uri n e G C R 
- 
e G F R 
•  
C h a n g e fr o m Bas eli n e t o W e ek 7 9 i n H b A1c 
•  
C h a n g e fr o m Bas eli n e t o W e ek 7 9 i n F P G 
•  
C h a n g e fr o m Bas eli n e t o W e ek 2 6 i n S B P f or all p ati e nts 
a n d f or p ati e nts wit h Bas eli n e S B P ≥1 3 0 m m H g 
 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 0 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 0 
•  
C h a n g e fr o m Bas eli n e t o W e ek 7 9 i n S B P f or all p ati e nts 
a n d f or p ati e nts wit h Bas eli n e S B P ≥1 3 0 m m H g 
•  
C h a n g e fr o m Bas eli n e t o W e ek 7 9 i n b o dy w ei g ht 
S af et y e n d p oi nt s: 
•  
Adv ers e ev e nts ( A Es), hy p o glyc e mi a ( all, s ev er e, a n d/ or 
d oc u m e nt e d sy m pt o m atic hy p o glyc e mi a), E O SI, A E SI, 
A Es l e a di n g t o disc o nti n u ati o n fr o m t h e I M P, S A Es, a n d 
d e at hs 
•  
Cli nic al l a b or at ory r es ults, i ncl u di n g f asti n g li pi ds, vit al 
si g ns, a n d el ectr oc ar di o gr a m ( E C G) r es ults 
•  
M ark ers of b o n e a n d c alci u m m et a b olis m 
•  
M ark ers of i nt esti n al tr a nsit a n d a bs or pti o n 
P h ar m a c o ki n eti c e n d p oi nt s:  
•  
Pl as m a c o nc e ntr ati o ns of s ot a glifl ozi n a n d its m et a b olit e 
pr e- d os e at W e eks 4, 1 8, 2 6, 5 2, 7 9 a n d 2 h o urs 3 0 
mi n ut es p ost- d os e at W e eks 2 6 a n d 7 9 
E n d p oi nt s of A B P M s u b st u d y: 
Pri m ary e n d p oi nt: 
•  
T h e pri m ary e n d p oi nt of t h e A B P M s u bst u dy is t h e c h a n g e 
fr o m B as eli n e t o W e ek 1 2 i n av er a g e 2 4-h o ur S B P i n a 
s u bs et of p ati e nts wit h m e a n S B P ≥1 3 0 m m H g at 
Scr e e ni n g 
Se c o n d ary e n d p oi nt s: 
•  
C h a n g e fr o m Bas eli n e t o W e ek 2 6 i n av er a g e 2 4- h o ur 
S B P 
•  
C h a n g e fr o m Bas eli n e t o W e ek 1 2 a n d 2 6 i n av er a g e 
2 4- h o ur D B P 
•  
C h a n g e fr o m Bas eli n e t o W e ek 1 2 a n d 2 6 i n av er a g e 
a dj ust e d a w ak e ti m e B P as m e as ur e d by S B P a n d D B P 
wit h a dj ust m e nt b as e d o n acti gr a p hy 
•  
C h a n g e fr o m Bas eli n e t o W e ek 1 2 a n d 2 6 i n av er a g e 
a dj ust e d sl e e p ti m e B P as m e as ur e d by S B P a n d D B P 
wit h a dj ust m e nt b as e d o n acti gr a p hy 
A S S E S S M E N T S C H E D U L E 
Se e St u dy Fl o w C h art Secti o n 1. 2  
S T A TI S TI C A L C O N SI D E R A TI O N S 
 
S a m pl e si z e d et er mi n ati o n: 
T h e s a m pl e siz e/ p o w er c alc ul ati o ns ar e b as e d o n t h e pri m ary 
v ari a bl e, c h a n g e fr o m Bas eli n e t o W e ek 2 6 i n H b A1c. 
Ass u mi n g a c o m m o n st a n d ar d d evi ati o n ( S D) of 1. 2 % a n d usi n g a 
2-si d e d t est at a 0. 0 5 α -l ev el, 2 5 0 p ati e nts p er ar m will h av e at l e ast 
9 9 % p o w er t o d et ect a tr e at m e nt diff er e nc e of 0. 6 % i n m e a n H b A 1c 
c h a n g e fr o m Bas eli n e t o W e ek 2 6 b et w e e n s ot a glifl ozi n 4 0 0 m g a n d 
pl ac e b o. 
T h e s a m pl e siz e/ p o w er c alc ul ati o ns f or A B P M s u bst u dy ar e b as e d 
o n t h e pri m ary v ari a bl e, c h a n g e fr o m Bas eli n e t o W e ek 1 2 i n 
av er a g e 2 4- h o ur S B P i n p ati e nts wit h m e a n S B P ≥1 3 0 m m H g at 
Scr e e ni n g. Ass u mi n g a c o m m o n S D of 1 5 m m H g a n d usi n g a 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 1 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 1 
2-si d e d t est at a 0. 0 5 α -l ev el, 1 0 0 p ati e nts p er ar m will pr ovi d e 
9 0 % p o w er t o d et ect a tr e at m e nt diff er e nc e of 7 m m H g i n av er a g e 
2 4- h o ur S B P c h a n g e fr o m B as e li n e t o W e ek 1 2 b et w e e n 
s ot a glifl ozi n 4 0 0 m g a n d pl ac e b o. 
A n al y si s p o p ul ati o n: 
Effic acy a n alys es will b e b as e d o n t h e i nt e nti o n t o tr e at (I T T) 
p o p ul ati o n, d efi n e d as all r a n d o miz e d p ati e nts, irr es p ectiv e of 
c o m pli a nc e wit h t h e st u dy pr ot oc ol a n d pr oc e d ur es. 
Pri m ar y a n al y si s: 
An alysis of t h e pri m ary effic acy e n d p oi nt (c h a n g e fr o m Bas eli n e t o 
W e ek 2 6 i n H b A1c) will b e p erf or m e d o n t h e I T T p o p ul ati o n, usi n g 
H b A1c m e as ur e m e nts o bt ai n e d d uri n g t h e st u dy, i ncl u di n g t h os e 
o bt ai n e d aft er I M P disc o nti n u ati o n or i ntr o d ucti o n of r esc u e t h er a py. 
T h e pri m ary effic acy e n d p oi nt of c h a n g e i n H b A1c fr o m b as eli n e t o 
W e ek 2 6 will b e a n alyz e d wit h missi n g v al u es i m p ut e d by 
c o ntr ol- b as e d m ulti pl e i m p ut ati o n m et h o d u n d er t h e missi n g n ot at 
r a n d o m fr a m e w ork.  
•  
F or pl ac e b o p ati e nts, missi n g d at a will b e i m p ut e d b as e d 
o n t h e pl ac e b o gr o u p d at a, 
•  
F or p ati e nts i n t h e s ot a glifl ozi n gr o u p, missi n g d at a will b e 
i m p ut e d as if t h e p ati e nts w er e o n pl ac e b o t hr o u g h o ut t h e 
st u dy. 
Eac h of t h e c o m pl et e d at as ets will b e a n alyz e d by a n An alysis of 
C ov ari a nc e ( A N C O V A) m o d el wit h tr e at m e nt gr o u ps (s ot a glifl ozi n, 
pl ac e b o), r a n d o miz ati o n str at u m of H b A1c ( ≤8. 0 %, > 8. 0 %), 
r a n d o miz ati o n str at u m of S B P ( < 1 3 0, ≥1 3 0 m m H g), a n d c o u ntry as 
fix e d eff ects, a n d b as eli n e H b A1c v al u e as a c ov ari at e. R es ults fr o m 
e ac h c o m pl et e d at as et will b e c o m bi n e d t o pr ovi d e t h e a dj ust e d 
m e a n c h a n g e i n H b A1c fr o m Bas eli n e t o W e ek 2 6 f or e ac h tr e at m e nt 
gr o u p, as w ell as t h e b et w e e n- gr o u p diff er e nc e (c o m p ari n g 
s ot a glifl ozi n vs pl ac e b o) a n d t h e 9 5 % c o nfi d e nc e i nt erv als ( CI) f or 
t h e diff er e nc e.  
Su m m ary st atistics (f or scr e e ni n g v al u e, b as eli n e v al u e, o bs erv e d 
v al u es, a n d o bs erv e d c h a n g es fr o m B as eli n e) at sc h e d ul e d visits will 
b e pr ovi d e d f or e ac h tr e at m e nt gr o u p. T h e s u m m ary will i ncl u d e t h e 
n u m b er of o bs erv ati o ns, m e a n, S D, st a n d ar d err or ( S E), mi ni m u m, 
m e di a n, a n d m axi m u m. Gr a p hic al pr es e nt ati o ns will als o b e us e d t o 
ex a mi n e tr e n ds ov er ti m e us i n g m e a n v al u es ( ± S E) a n d m e a n 
c h a n g es fr o m Bas eli n e ( ± S E) at e ach of t h e sc h e d ul e d visits ( usi n g 
o bs erv e d c as es [ O C]). 
A n al y si s of s e c o n d ar y effi c a c y e n d p oi nt s: 
T h e s ec o n d ary e n d p oi nts will b e a n alyz e d usi n g a si mil ar a p pr o ac h 
t o t h e pri m ary effic acy e n d p oi nt, wit h missi n g v al u es i m p ut e d by 
c o ntr ol- b as e d m ulti pl e i m p ut ati o n m et h o d u n d er t h e missi n g n ot at 
r a n d o m fr a m e w ork.  
F or e ac h of t h e c o nti n u o us s ec o n d ary e n d p oi nt, e ac h of t h e 
c o m pl et e d at as ets will b e a n alyz e d by t h e A N C O V A m o d el wit h 
tr e at m e nt gr o u ps (s ot a glifl ozi n, pl ac e b o), r a n d o miz ati o n str at u m of 
H b A 1c ( ≤8. 0 %, > 8. 0 %), r a n d o miz ati o n str at u m of S B P ( < 1 3 0 m m H g, 
≥1 3 0 m m H g), a n d c o u ntry as fix e d eff ects, a n d b as eli n e s ec o n d ary 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 2 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 2 
e n d p oi nt v al u e as a c ov ari at e. R es ults fr o m e ac h c o m pl et e d at as et 
will b e c o m bi n e d t o pr ovi d e t h e a dj ust e d m e a n c h a n g e fr o m B as eli n e 
t o W e ek 2 6 f or e ac h tr e at m e nt gr o u p, as w ell as t h e b et w e e n- gr o u p 
diff er e nc e (c o m p ari n g s ot a glifl ozi n vs pl ac e b o) a n d t h e 9 5 % CI f or 
t h e diff er e nc e. 
T h e c at e g oric al s ec o n d ary effic acy v ari a bl es of H b A1c < 6. 5 %, 
< 7 % at W e ek 2 6 will b e a n alyz e d usi n g a C oc hr a n- M a nt el- H a e nsz el 
m et h o d str atifi e d by r a n d o miz ati o n str at u m of H b A1c ( ≤8. 0 %, 
> 8. 0 %), a n d r a n d o miz ati o n str at u m of S B P ( < 1 3 0, ≥1 3 0 m m H g). 
A n al y si s of ot h er effi c a c y e n d p oi nt s:  
T h e a n alysis of ot h er e n d p oi nts will b e d escri ptiv e wit h n o f or m al 
t esti n g. S u m m ary st atistics at sc h e d ul e d visits usi n g O C will b e 
pr ovi d e d by e ac h tr e at m e nt gr o u p. Gr a p hic al pr es e nt ati o ns will als o 
b e us e d t o ill ustr at e tr e n ds ov er ti m e. 
A n al y s e s of s af et y d at a:  
All s af ety s u m m ari es will b e d escri ptiv e; n o st atistic al si g nific a nc e 
t ests will b e p erf or m e d o n s af ety d at a. T h es e a n alys es will b e b as e d 
o n t h e Saf ety Po p ul ati o n, w hic h is d efi n e d as all r a n d o miz e d p ati e nts 
w h o r ec eiv e at l e ast 1 d os e of d o u bl e- bli n d tr e at m e nt, r e g ar dl ess of 
t h e a m o u nt of tr e at m e nt a d mi nist er e d. Pati e nts will b e a n alyz e d f or 
s af ety a n alys es acc or di n g t o t h e tr e at m e nt act u ally r ec eiv e d. T h e 
s af ety a n alys es will b e pr ovi d e d f or t h e 2 6- w e ek c or e tr e at m e nt 
p eri o d a n d f or t h e e ntir e tr e at m e nt p eri o d. 
A n al y si s of A B P M s u b st u d y e n d p oi nt s: 
A B P M s u bst u dy e n d p oi nts will b e a n alyz e d usi n g a si mil ar a p pr o ac h 
as t h e pri m ary effic acy e n d p oi nt wit h missi n g v al u es i m p ut e d by 
c o ntr ol- b as e d m ulti pl e i m p ut ati o n m et h o d u n d er t h e missi n g n ot at 
r a n d o m fr a m e w ork. E ac h of t h e c o m pl et e d at as et will b e a n alyz e d 
usi n g A N C O V A m o d el i ncl u di n g f act ors f or tr e at m e nt (s ot a glifl ozi n, 
pl ac e b o), r a n d o miz ati o n str at u m of H b A1c ( ≤8. 0 %, > 8. 0 %) as fix e d 
eff ects, a n d t h e b as eli n e v al u e of t h e s p ecific d e p e n d e nt v ari a bl e as 
a c ov ari at e.  
D U R A TI O N O F S T U D Y P E RI O D ( p er 
p ati e nt)  
U p t o 8 7 w e eks, i ncl u di n g a Scr e e ni n g Peri o d c o nsisti n g of a 
Scr e e ni n g p h as e of u p t o 2 w e eks a n d a 2- w e ek si n gl e- bli n d R u n-i n 
p h as e, a 2 6- w e ek d o u bl e- bli n d C or e  Tr e at m e nt Peri o d, a 5 3- w e ek 
d o u bl e- bli n d Ext e nsi o n Peri o d, a 4- w e ek p ost tr e at m e nt F oll o w- u p 
p eri o d t o c oll ect s af ety i nf or m ati o n. 
S T U D Y C O M MI T T E E S 
St e eri n g c o m mitt e e:  
 Y es    
 N o 
D at a m o nit ori n g c o m mitt e e: 
 Yes    
 N o 
Cli ni c al E n d p oi nt C o m mitt e e s:  
 Yes    
 N o 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 3 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 3 
1  
F L O W C H A R T S 
1. 1  
G R A P HI C A L S T U D Y D E SI G N 
 
 
 
A b brevi ati o ns: A B P M: a m b ul at or y bl o o d press ure m o nit ori n g; H b A 1c: h e m o gl o bi n A 1c; R: ra n d o miz ati o n; T 2 D: ty p e 2 di a b et es m ellit us. 
( el e ctr o ni c 
 
 
2. 0)
( el e ctr o ni c 
 
 
1. 0)
Pa ge 1 4 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 4 
1. 2  
S T U D Y F L O W C H A R T 
S cr e e ni n g P eri o d  
 
S cr e e ni n g  
R u n-i n 
D o u bl e- Bli n d C or e Tr e at m e nt P eri o d a 
D o u bl e- Bli n d E xt e n si o n 
P eri o d b  
F oll o w-
u p  
VI SI T 
1  
2  
3 A ( A B P M 
pl a c e m e nt) c  
3 
( R a n d o m
-iz ati o n) 
4  
5  
6  
7 A ( A B P M 
pl a c e m e nt) c  
7  
8  
9 A ( A B P M 
pl a c e m e nt) c  
9  
1 0  
1 1  
1 2  
1 3 
1 4 d 
W e e k 
U p t o - 4  
- 2  
- 1  
0 
B a s eli n e 
1  
4  
8  
1 2  
1 2  
1 8  
2 6  
2 6  
3 9  
5 2  
6 5  
7 9  
8 3 
Da y ( wi n d o w [ d a y s])  
  
 
(- 7/ 
+ 3) 
- 7  
( ± 2) 
1  
7 
( ± 3) 
2 8 
( ± 3) 
5 6 
( ± 3) 
8 3  
( ± 2) 
8 4 
( ± 3) 
1 2 6 
( ± 3) 
1 8 1  
( ± 2) 
1 8 2 
( ± 3) 
2 7 3 
( ± 7) 
3 6 5 
( ± 7) 
4 5 5 
( ± 7) 
5 5 1  
(-3 t o + 4) 
5 7 9 
( ± 3) 
I nf or m e d
 
c o ns e nt
  
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I ncl usi o n
 
crit eri a
  
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Excl usi o n
 
crit eri a
  
X
 
 
 
 
  
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
D e m o gra p hics
  
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
M e dic al/ S ur gic al
 
Hist ory
  
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
M e dic ati o n
 
Hist ory
  
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
H e p atitis
 
s er ol o gy
  
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
B o dy w ei g ht, h ei g ht e 
X
  
X
 
 
  
X
  
X
  X
  X
 
 
  
X
 X
 
 
  
X
 X
 X
 X
  
X
  
X
 
Vit al si g ns f 
X
  
X
 
 
  
X
  
X
  X
  X
 
 
  
X
 X
 
 
  
X
 X
 X
 X
  
X
  
X
 
P hysic al
 
Ex a mi n ati o n:
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C o m pl et e
 
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
X
 
 
 
  X
 
 
 
A b brevi at e d
 
  
X
 
 
  
X
  
X
  X
  X
 
 
  
X
 X
 
 
 
 
  X
 X
 X
 
 
  
X
 
Di et & ex ercis e i nstructi o n  
  
X  
  
X  
  
  
  
  
  
  
  
X  
  
X  
  
X  
 
I nstr ucti o n o n b asic 
g e nit o uri n ary hy gi e n e & 
hy dr ati o n 
  
X
 
 
  
X
  
X
  X
  X
 
 
  
X
 X
 
 
  
X
 X
 X
 X
  
X
 
 
 
( el e ctr o ni c 
 
 
2. 0)
( el e ctr o ni c 
 
 
1. 0)
Pa ge 1 5 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 5 
S cr e e ni n g P eri o d  
 
S cr e e ni n g  
R u n-i n 
D o u bl e- Bli n d C or e Tr e at m e nt P eri o d a 
D o u bl e- Bli n d E xt e n si o n 
P eri o d b  
F oll o w-
u p  
VI SI T 
1  
2  
3 A ( A B P M 
pl a c e m e nt) c  
3 
( R a n d o m
-iz ati o n) 
4  
5  
6  
7 A ( A B P M 
pl a c e m e nt) c  
7  
8  
9 A ( A B P M 
pl a c e m e nt) c  
9  
1 0  
1 1  
1 2  
1 3 
1 4 d 
W e e k 
U p t o - 4  
- 2  
- 1  
0 
B a s eli n e 
1  
4  
8  
1 2  
1 2  
1 8  
2 6  
2 6  
3 9  
5 2  
6 5  
7 9  
8 3 
Da y ( wi n d o w [ d a y s])  
  
 
(- 7/ 
+ 3) 
- 7  
( ± 2) 
1  
7 
( ± 3) 
2 8 
( ± 3) 
5 6 
( ± 3) 
8 3  
( ± 2) 
8 4 
( ± 3) 
1 2 6 
( ± 3) 
1 8 1  
( ± 2) 
1 8 2 
( ± 3) 
2 7 3 
( ± 7) 
3 6 5 
( ± 7) 
4 5 5 
( ± 7) 
5 5 1  
(-3 t o + 4) 
5 7 9 
( ± 3) 
I R T c o nt actg 
X
  
X
 
 
  
X
 
 
  X
  X
 
 
  
X
 X
 
 
  
X
 X
 X
 X
  
X
  
X
 
R a n d o miz ati o n
 
 
 
 
 
  
X
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dis p e ns e gl uc os e m et er   
  
X  
 
  
  
  
  
  
  
  
  
  
  
  
  
 
 
Dis p e ns e
 
di ary
 
X
  
X
 
 
  
X
  
X
  X
  X
 
 
  
X
 X
 
 
  
X
 X
 X
 X
  
X
 
 
 
C oll ect/revi e w
 
di ary
 
 
  
X
 
 
  
X
  
X
  X
  X
 
 
  
X
 X
 
 
  
X
 X
 X
 X
  
X
  
X
 
I nstr ucti o n o n di a b etic 
k et o aci d osis sy m pt o ms, 
gl uc os e t esti n g 
 
 
 
 
  
X
  
X
  X
  X
 
 
  
X
 X
 
 
  
X
 X
 X
 X
  
X
 
 
 
Dis p e ns e
 
I M P
  
  
X
 
 
  
X
 
 
  X
  X
 
 
  
X
 X
 
 
  
X
 X
 X
 X
 
 
 
 
 
I M P acc o u nti n g & 
c o m pli a nc e 
 
 
 
X
  
X
  X
  X
 
 
  
X
 X
 
 
  
X
 X
 X
 X
  
X
 
 
C o nc o mit a nt
 
M e dic ati o n
  
X
  
X
 
 
  
X
  
X
  X
  X
 
 
  
X
 X
 
 
  
X
 X
 X
 X
  
X
  
X
 
S elf- m o nit ori n g of bl o o d 
gl uc os e h 
  
X
 
 
  
X
  
X
  X
  X
 
 
  
X
 X
 
 
  
X
 X
 X
 X
  
X
  
X
 
1 2-l e a d E C G i 
X
 
 
 
 
  
X
 
 
 
 
 
 
 
 
 
 
 
  
X
 
 
 
  X
 
 
 
St a n d ar d mix e d m e al 
t ol er a nc e t estj 
 
 
 
 
  
X
 
 
 
 
 
 
 
 
 
 
 
  
X
 
 
 
  X
 
 
 
L a b or at or y te sti n g k 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
F P G
 
X
 
 
 
 
  
X
  
X
  X
  X
 
 
  
X
 X
 
 
  
X
 X
 X
 X
  
X
 
 
 
( el e ctr o ni c 
 
 
2. 0)
( el e ctr o ni c 
 
 
1. 0)
Pa ge 1 6 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 6 
S cr e e ni n g P eri o d  
 
S cr e e ni n g  
R u n-i n 
D o u bl e- Bli n d C or e Tr e at m e nt P eri o d a 
D o u bl e- Bli n d E xt e n si o n 
P eri o d b  
F oll o w-
u p  
VI SI T 
1  
2  
3 A ( A B P M 
pl a c e m e nt )c  
3 
( R a n d o m
-iz ati o n) 
4  
5  
6  
7 A ( A B P M 
pl a c e m e nt) c  
7  
8  
9 A ( A B P M 
pl a c e m e nt) c  
9  
1 0  
1 1  
1 2  
1 3 
1 4 d 
W e e k 
U p t o - 4  
- 2  
- 1  
0 
B a s eli n e 
1  
4  
8  
1 2  
1 2  
1 8  
2 6  
2 6  
3 9  
5 2  
6 5  
7 9  
8 3 
Da y ( wi n d o w [ d a y s])  
  
 
(- 7/ 
+ 3) 
- 7  
( ± 2) 
1  
7 
( ± 3) 
2 8 
( ± 3) 
5 6 
( ± 3) 
8 3  
( ± 2) 
8 4 
( ± 3) 
1 2 6 
( ± 3) 
1 8 1  
( ± 2) 
1 8 2 
( ± 3) 
2 7 3 
( ± 7) 
3 6 5 
( ± 7) 
4 5 5 
( ± 7) 
5 5 1  
(-3 t o + 4) 
5 7 9 
( ± 3) 
H b A 1c
 
X
 
 
 
 
  
X
 
 
  X
  X
 
 
  
X
 X
 
 
  
X
 X
 X
 X
  
X
 
 
 
C h e mistry (i ncl u di n g 
a myl as e a n d li p as e) 
X
 
 
 
 
  
X
 
 
  X
  X
 
 
  
X
 X
 
 
  
X
 X
 X
 X
  
X
  
X
 
H e m at ol o gy
 
X
 
 
 
 
  
X
 
 
 
 
 
 
 
 
  
X
 
 
 
 
  
X
 X
 X
 X
  
X
 
 
 
F asti n g
 
li pi ds
  
X
 
 
 
 
  
X
 
 
 X
 X
 
 
  
X
 X
 
 
  
X
 
 
 
  X
 
 
 
Pr e g n a ncy t est 
( W O C B P)l 
X
 
 
 
 
  
X
 
 
  X
  X
 
 
  
X
 X
 
 
  
X
 X
 X
 X
  
X
 
 
S eru m f ollicl e 
sti m ul ati n g h or m o n e 
a n d estr a di ol 
( m e n o p a us al w o m e n 
o nly) l 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pl as m a c o nc e ntr ati o n m  
 
 
 
 
 
 
X
 
 
 
 
 
 X
 
 
  
X
  
X 
 
X 
 
M ark ers of i nt esti n al 
tr a nsit & a bs orpti o nn 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
X
 
 
 
  X
  
X
 
M ark ers of b o n e & 
c alci u m m et a b olis mo 
 
 
 
X
 
 
 
 
 
 
 
 
 
 
 
  
X
 
 
 
  X
 
 
 
Uri n alysis ( di pstick a n d 
microsc o py) p 
X
 
 
 
 
  
X
 
 
 
 
 
 
 
 
 
 
 
  
X
 
 
 
  X
 
 
 
( el e ctr o ni c 
 
 
2. 0)
( el e ctr o ni c 
 
 
1. 0)
Pa ge 1 7 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 7 
S cr e e ni n g P eri o d  
 
S cr e e ni n g  
R u n-i n 
D o u bl e- Bli n d C or e Tr e at m e nt P eri o d a 
D o u bl e- Bli n d E xt e n si o n 
P eri o d b  
F oll o w-
u p  
VI SI T 
1  
2  
3 A ( A B P M 
pl a c e m e nt) c  
3 
( R a n d o m
-iz ati o n) 
4  
5  
6  
7 A ( A B P M 
pl a c e m e nt) c  
7  
8  
9 A ( A B P M 
pl a c e m e nt) c  
9  
1 0  
1 1  
1 2  
1 3 
1 4 d 
W e e k 
U p t o - 4  
- 2  
- 1  
0 
B a s eli n e 
1  
4  
8  
1 2  
1 2  
1 8  
2 6  
2 6  
3 9  
5 2  
6 5  
7 9  
8 3 
Da y ( wi n d o w [ d a y s])  
  
 
(- 7/ 
+ 3) 
- 7  
( ± 2) 
1  
7 
( ± 3) 
2 8 
( ± 3) 
5 6 
( ± 3) 
8 3  
( ± 2) 
8 4 
( ± 3) 
1 2 6 
( ± 3) 
1 8 1  
( ± 2) 
1 8 2 
( ± 3) 
2 7 3 
( ± 7) 
3 6 5 
( ± 7) 
4 5 5 
( ± 7) 
5 5 1  
(-3 t o + 4) 
5 7 9 
( ± 3) 
Uri n e al b u mi n, c alci u m, 
gl uc os e & cre ati ni n e 
 
 
 
X
  
X
  X
  X
 
 
  
X
 X
 
 
  
X
 X
 X
 X
  
X
  
X
 
A B P M pl ac e m e nt c 
 
 
X
 
 
 
 
 
 
  
X
 
 
 
  
X
 
 
  
 
 
 
 
 
 
A B P M r e m ov al a n d 
ass ess m e nt  
 
 
 
X
 
 
 
 
 
 
  
X
 
 
 
  
X
  
 
 
 
 
 
 
Ev al u at e f or glyc e mic 
r esc u e 
 
 
 
 
 
T o b e ass ess e d a n d r e p ort e d t hr o u g h o ut t h e tr e at m e nt p eri o d 
 
Hy p o glyc e mi a 
T o b e ass ess e d a n d r e p ort e d t hr o u g h o ut t h e st u dy 
A Es/ S A Es/ A E SIs/ E O SIs 
T o b e ass ess e d a n d r e p ort e d t hr o u g h o ut t h e st u dy s 
a  If a p ati e nt disc o nti n u es tr e at m e nt wit h i nv esti g ati o n al m e dici n al pr o d uct (I M P) e arly d uri n g t h e C or e Tr e at m e nt P eri o d, t h e p ati e nt will h av e a Pre mat ure E n d-of- Tre at m e nt ( E O T ) Visit, a n d a F oll o w-u p Visit 4 
we eks aft er t h e l ast d os e of I M P. I n a d diti o n, ev ery eff ort w ill b e m a d e t o h av e all p ati e nts ret urn t o t h e sit e at t h e ti m e c orres p o n di n g t o t h eir sc h e d ul e d visits, p artic ul arly t h e W e ek 2 6 Visit. If t h e p ati e nt d o es n ot 
a gre e t o a sit e visit, t h ey will b e c o nt act e d by t el e p h o n e t o i n q uire a b o ut s af ety st at us. If a p ati e nt disc o nti n u es ( or c o m pl et es) tre at m e nt a n d st u dy at t h e s a m e ti m e, a si n gl e visit will b e p erf or m e d usi n g t h e 
pr oc e d ur e n or m ally pl a n n e d f or t h e E O T visit. 
b  If a p ati e nt c o m pl et es t h e C ore Tre at m e nt, b ut disc o nti n u es I M P d uri n g t h e Ext e nsi o n P eri o d, t h e p ati e nt will h av e a Pre m at ure E O T Visit, a n d a F oll o w-u p Visit 4 we eks aft er t h e l ast d os e of I M P. Ev ery eff ort will 
b e m a d e t o h av e all p ati e nts r et ur n t o t h e sit e at t h e ti m e c orres p o n di n g t o t h eir q u art erly visits (i e, ev ery 1 3 w e eks) d uri n g  t h e Ext e nsi o n P eri o d. At t h e ti m e c orres p o n di n g t o t h eir W e ek 7 9 Visit, all att e m pts will b e 
m a d e t o c o nt act t h e p ati e nt t o i n q uir e a b o ut s af ety st at us. If a p ati e nt disc o nti n u es ( or c o m pl et es) tr e at m e nt a n d st u dy at t h e  s a m e ti m e, a si n gl e visit will b e p erf or m e d usi n g t h e proc e d ur e n or m ally pl a n n e d f or t h e 
E O T visit. 
c A m b ul at ory Bl o o d Press ur e M o nit ori n g ( A B P M) s u bst u dy visits f or a s u bs et of p ati e nts will occ ur 1 w e ek b ef ore t h e ra n d o miz ati o n  Visit; p ati e nts will r et urn t h e A B P M d evice by p ost aft er 2 4-h o ur m o nit ori n g is 
c o m pl et e. P ati e nts i n t h e A B P M s u bst u dy will als o h av e visits f or pl ac e m e nt of t h e A B P M d evic e t h e d ay b ef ore W e ek 1 2 a n d W e ek 2 6 visits. 
( el e ctr o ni c 
 
 
2. 0)
( el e ctr o ni c 
 
 
1. 0)
Pa ge 1 8 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 8 
d  F o ur w e eks aft er t h e l ast d os e of I M P. 
e  H ei g ht t o b e m e as ure d o nly at scre e ni n g. 
f 
Vit al si g n m e as ur e m e nts (sitti n g B P a n d h e art r at e): 3 s e p ar at e s e at e d B P a n d h e art r at e m e as ur e m e nts s h o ul d b e t ak e n wit h at l e ast 1 mi n ut e b et w e e n r e a di n gs, f oll o wi n g a 5- mi n ut e r est p eri o d a n d pri or t o 
p hl e b ot o my (s e e  S ecti o n 9. 2. 1. 4  a n d d et ail e d i nstr ucti o ns i n A p p e n dix E ). 
g  I nt er activ e r es p o ns e T ec h n ol o gy (I R T) c o nt act n ot r e q uir e d f or p ati e nts w h o disc o nti n u e I M P e arly aft er t h ey h av e att e n d e d t h e E O T Visit.  
h  S e e S ecti o n  9. 2. 1. 6  f or d et ails of S M B G m e as ur e m e nts. Gl uc os e m et ers us e d f or S M B G dis pl ay r es ults as pl as m a gl uc os e c o nc e ntr ati o n. P ati e nts s h o uld m e as ur e t h eir f asti n g pl as m a gl uc os e at l e ast 3 ti m es p er 
w e ek (i ncl u di n g o n d ay of e ac h o n-sit e st u dy visit). Aft er Visit 9 ( W e ek 2 6), if f asti n g S M B G v al u es ar e < 1 2 0 m g/ d L, ov er a 2- w e ek p eri o d, t h e I nv esti g at or c a n i nstr uct p ati e nts t o s elf- m o nit or bl o o d gl uc os e o nc e a 
w e ek ( o n d ay of o n-sit e st u dy visit f or w e eks wit h o n-sit e st u dy visits). 
i 
T h e 1 2-l e a d E C G rec ordi n gs s h o ul d b e o bt ai n e d pri or t o I M P a d mi nistrati o n. T h e E C G will b e ev al u at e d as “n or m al” or “a b n or m al”. 
j 
P ost pra n di al pl as m a gl uc os e will b e ass ess e d by c e ntral l a b orat ory at B as eli n e a n d 2 h o urs aft er c o ns u mi n g a st a n d ard mix e d li q ui d br e akf ast m e al a n d vi a a mix e d m e al t ol er a nc e t est ( M M T T) o n D ay 1, W e ek 
2 6, a n d W e ek 7 9. If a p ati e nt wit h dra ws fr o m I M P e arly, pl e as e s e e S ecti o n  1 0. 3. 4 . 
k All l a b or at ory ass ess m e nts occ ur pri or t o first d os e of d o u bl e- bli n d I M P. T h e first d os e of d o u bl e-bli n d I M P occ urs aft er s a m pl es f or t h e mix e d li q ui d m e al h av e b e e n c oll ect e d. A ll visit d at es will b e sc h e d ul e d b as e d 
o n t h e d at e of r a n d o miz ati o n wit h a ± 3 d ays visit wi n d o w all o w e d d uri n g t h e c or e tre at m e nt p eri o d. S er u m c h e mistry p ar a m et ers ( cli nic al c h e mistry [incl u di n g a myl as e a n d li p as e], h e m at ol o gy, a n d ot h er bl o o d 
p ar a m et ers) ar e list e d i n T a bl e 2.   
l 
S er u m pre g n a ncy t esti n g o nly at scr e e ni n g; uri n e pr e g n a ncy t esti n g s u bs e q u e ntly. S er u m pr e g n a ncy t est r es ults m ust b e r evi e w e d pri or t o b e gi n ni n g t h e R u n-i n p h as e f or all w o m e n of c hil d b e ari n g p ot e nti al 
( W O C B P) u nl ess t h er e is d oc u m e nt e d hist ory of m e n o p a us e (b as e d o n d oc u me nt e d f ollicl e-sti m ul a ti n g h or m o n e [ F S H] a n d estra di ol lev els – if res ults n ot d oc u m e nt e d t h e n F S H a n d estr a di ol will b e t est e d at 
Scr e e ni n g visit) or t h ey ar e s ur gic ally st eril e. A ny p ositiv e uri n e t est r es ults m ust b e c o nfir m e d b as e d o n s er u m pre g n a ncy t est. T h e I nv esti g at or m ay p erf or m a d diti o n al t ests at t h eir discr eti o n or as r e q uir e d by 
l oc al r e g ul ati o ns. 
m  Pl as m a c o nc e ntr ati o n s a m pl es (i e, f or s ot a glifl ozi n a n d S ot a glifl ozi n- 3- O- gl uc ur o ni d e) o n W e ek 4, W e ek 1 8, a n d W e ek 5 2 s h o ul d b e dra w n wit h t h e ot h er l a b or at ory ass ess m e nts. F or W e ek 2 6 a n d W e ek 7 9, 
pl as m a c o nc e ntr ati o n s a m pl es s h o ul d b e dra w n at Ti m e 0 a n d 1 5 0 mi n ut es ( 2 h o ur 3 0 mi n ut es) i m m e di at ely aft er t h e r es p ectiv e gl u c os e ass ess m e nts d uri n g t h e M M T T. P h ar m ac oki n etic ( P K) s a m pl es ( exc e pt t h e 
2 h o ur 3 0 mi n ut e s a m pl e d uri n g t h e M M T T) M U S T b e c oll ect e d b ef or e a d mi nistr ati o n of I M P. T h e d at e a n d ti m e of t h e l ast i nt ak e o f I M P pri or t o visits w h er e P K s a m pl es are t ak e n s h o ul d b e r ec or d e d by t h e 
p ati e nt i n t h e p ati e nt di ary. P ati e nts s h o ul d b e r e mi n d e d of t his at visits pr ec e di n g P K ti m e p oi nts t o e ns ur e t h es e d et ails ar e c a pt ur e d. I n t h e c as e of pr e m at ur e I M P disc o nti n u ati o n, P K s a m pl es s h o ul d n ot b e 
dr a w n at t h e Pr e m at ure E O T visit, n or at a ny s u bs e q u e nt visits. 
n  T h e m ark ers of i nt esti n al tr a nsit a n d a bs or pti o n i ncl u d e vit a mi ns B 6, B 1 2, K, E, a n d A, s er u m f ol at e, a n d f erriti n. 
o  M ark ers of b o n e a n d c alci u m m et a b olis m i ncl u d e: s eru m a n d uri n ary c alci u m, s eru m 2 5-hy droxyvit a min D, s eru m 1, 2 5-di hy droxyvit a m i n D, s er u m a n d uri n ary p h os p h or us, s er u m p ar at hyroi d h or m o n e, m ark ers of 
b o n e r es or pti o n  (ser u m N T X, s er u m β - C T X- 1), a n d b o n e f or m ati o n (s er u m P 1 N P). 
p  Uri n alysis i ncl u d es uri n e di pstick a n d microsc o py. Di pstick i ncl u d es ass ess m e nt of s p ecific gr avity, p H, pr ot ei n, bl o o d, k et o n e s, biliru bi n, uro bili n o g e n, nitrite, a n d l e uk ocyt e est eras e. Micr osc o py i n cl u d es d et ecti o n 
of f or m e d c ell ul ar el e m e nts, c asts, b act eri a, y e ast, p ar asit es, a n d cryst als i n c e ntrif u g e d uri n e s e di m e nt. I n t h e ev e nt of a b n or m al uri n alysis fi n di n gs s us pici o us of uri n ary tract i nf ecti o n, uri n e c ult ur e s h o ul d b e 
p erf or m e d. P ositiv e uri n e c ult ure d et er mi n ati o n will b e b as e d u p o n t h e crit eri a of t h e re p orti n g l a b orat ory. 
 
 
 
s All s eri o us a dv ers e ev e nts ( S A Es), a dv ers e ev e nts ( A Es), A Es of s p eci al i nt erest ( A E SI s), a n d Ev e nts of S p eci al I nt erest ( E O SIs) will b e c oll ect e d st arti n g wit h si g ni n g i nf or m e d c o ns e nt a n d c o nti n u e u ntil t h e e n d 
of t h e st u dy. All A Es t h at occ ur d uri n g tr e at m e nt s h o ul d b e f oll o w e d u ntil st u dy c o m pl eti o n ( or u ntil p ati e nts l e av e t h e st u dy)  or u ntil t h e ev e nt h as res olv e d, t h e c o n diti o n h as st a biliz e d, or t h e p ati e nt is l ost t o 
f oll o w-u p. All p ati e nts will h av e a f oll o w-u p visit 4 w e eks aft er t h e l ast d os e of I M P t o c oll ect s af ety i nf or m ati o n. 
( el e ctr o ni c 
 
 
2. 0)
( el e ctr o ni c 
 
 
1. 0)
Pa ge 1 9 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 9 
2  
T A B L E O F C O N T E N T S 
 
1  
F L O W C H A R T S.................................................................................................................... .........1 3  
1. 1  
G R A P HI C A L S T U D Y D E SI G N ...................................................................................................... 1 3  
1. 2  
S T U D Y F L O W C H A R T .................................................................................................................. 1 4  
2  
T A B L E O F C O N T E N T S ................................................................................................................ 1 9  
2. 1  
LI S T O F T A B L E S................................................................................................................. ..........2 5  
2. 2  
LI S T O F FI G U R E S......................................................................................................................... 2 5  
3  
LI S T O F A B B R E VI A TI O N S .......................................................................................................... 2 6  
4  
I N T R O D U C TI O N A N D R A TI O N A L E.............................................................................................2 8  
4. 1  
B A C K G R O U N D: S O T A G LI F L O ZI N A N D DI S E A S E ..................................................................... 2 8  
4. 2  
C LI NI C A L T RI A L S O F S O T A G LI F L O ZI N I N H U M A N S ................................................................ 2 9  
4. 3  
R A TI O N A L E F O R S E L E C TI O N O F D O S E ................................................................................... 3 0  
4. 4  
R A TI O N A L E F O R S T U D Y D E SI G N A N D C O N T R O L G R O U P S .................................................. 3 0  
4. 5  
R A TI O N A L E F O R A M B U L A T O R Y B L O O D P R E S S U R E M O NI T O RI N G S U B S T U D Y ................ 3 1  
4. 6  
B E N E FI T/ RI S K O F S O T A G LI F L O ZI N ........................................................................................... 3 1  
5  
S T U D Y O B J E C TI V E S ............................................................................................................... ....3 3  
5. 1  
P RI M A R Y........................................................................................................................ ...............3 3  
5. 2  
S E C O N D A R Y ...................................................................................................................... ..........3 3  
5. 3  
O T H E R........................................................................................................................................... 3 3  
5. 4  
A M B U L A T O R Y B L O O D P R E S S U R E M O NI T O RI N G S U B S T U D Y .............................................. 3 4  
6  
S T U D Y D E SI G N ................................................................................................................... .........3 5  
6. 1  
D E S C RI P TI O N O F T H E S T U D Y ................................................................................................... 3 5  
6. 1. 1  
S cr e e ni n g P eri o d............................................................................................................... .............3 5  
6. 1. 1. 1  
S cr e e ni n g p h a s e ( Vi sit 1) ...............................................................................................................3 5  
6. 1. 1. 2  
R u n-i n p h a s e ( Vi sit 2)..................................................................................................................... 3 6  
6. 1. 2  
D o u bl e- bli n d C or e Tr e at m e nt P eri o d ( W e e k 0 t o W e e k 2 6) .......................................................... 3 6  
6. 1. 3  
D o u bl e- bli n d E xt e n si o n P eri o d ( W e e k 2 7 t o W e e k 7 9).................................................................. 3 6  
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 2 0 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 2 0 
6. 1. 4  
A m b ul at or y bl o o d pr e s s ur e  m o nit ori n g s u b st u d y...........................................................................3 7  
 
3 7  
6. 1. 6  
F oll o w- u p p eri o d............................................................................................................... ..............3 7  
6. 2  
D U R A TI O N O F S T U D Y P A R TI CI P A TI O N .................................................................................... 3 7  
6. 2. 1  
D ur ati o n of st u d y p arti ci p ati o n f or e a c h p ati e nt ............................................................................. 3 7  
6. 2. 2  
D et er mi n ati o n of e n d of cli n i c al tri al ( all p ati e nt s) ..........................................................................3 8  
6. 3  
I N T E RI M A N A L Y SI S......................................................................................................................3 8  
6. 4  
S T U D Y C O M MI T T E E S ............................................................................................................... ...3 8  
6. 4. 1  
D at a m o nit ori n g c o m mitt e e ...................................................................................................... ......3 8  
6. 4. 2  
Cli ni c al e n d p oi nt c o m mitt e e( s)................................................................................................. ......3 8  
6. 4. 3  
S af et y a dj u di c ati o n of e v e nt s r e q uiri n g o n g oi n g m o nit ori n g .......................................................... 3 8  
6. 4. 4  
St e eri n g C o m mitt e e ............................................................................................................. ..........3 9  
7  
S E L E C TI O N O F P A TI E N T S.......................................................................................................... 4 0  
7. 1  
I N C L U SI O N C RI T E RI A..................................................................................................................4 0  
7. 2  
E X C L U SI O N C RI T E RI A ................................................................................................................ 4 0  
7. 2. 1  
E x cl u si o n crit eri a r el at e d t o st u d y m et h o d ol o g y ............................................................................ 4 0  
7. 2. 2  
E x cl u si o n crit eri a r el at e d t o di a b et e s hi st or y a n d tr e at m e nt .......................................................... 4 1  
7. 2. 3  
E x cl u si o n crit eri a r el at e d t o t h e c u rr e nt k n o wl e d g e of s ot a glifl o zi n ...............................................4 2  
7. 2. 4  
A d diti o n al e x cl u si o n crit eri a d ur i n g or at t h e e n d of t h e R u n-i n p h a s e b ef or e R a n d o mi z ati o n ......4 2  
8  
S T U D Y T R E A T M E N T S ............................................................................................................... ..4 4  
8. 1  
I N V E S TI G A TI O N A L M E DI CI N A L P R O D U C T S.............................................................................4 4  
8. 2  
N O NI N V E S TI G A TI O N A L M E DI CI N A L P R O D U C T ....................................................................... 4 4  
8. 2. 1  
M etf or mi n ....................................................................................................................................... 4 4  
8. 2. 2  
R e s c u e t h er a p y .............................................................................................................................. 4 5  
8. 3  
B LI N DI N G P R O C E D U R E S............................................................................................................ 4 6  
8. 3. 1  
M et h o d s of bli n di n g ........................................................................................................................ 4 6  
8. 3. 2  
R a n d o mi z ati o n c o d e br e a ki n g d uri n g t h e st u d y............................................................................. 4 7  
8. 4  
M E T H O D O F A S SI G NI N G P A TI E N T S T O T R E A T M E N T G R O U P .............................................. 4 7  
8. 5  
P A C K A GI N G A N D L A B E LI N G ...................................................................................................... 4 8  
8. 6  
S T O R A G E C O N DI TI O N S A N D S H E L F LI F E ................................................................................ 4 8  
8. 7  
R E S P O N SI BI LI TI E S ............................................................................................................... .......4 8  
8. 7. 1  
Tr e at m e nt a c c o u nt a bi lit y a n d c om pli a n c e...................................................................................... 4 9  
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 2 1 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 2 1 
8. 7. 2  
R et ur n a n d/ or d e str u cti o n of tr e at m e nt s ........................................................................................ 4 9  
8. 8  
C O N C O MI T A N T M E DI C A TI O N..................................................................................................... 5 0  
8. 8. 1  
Pr o hi bit e d pri or a n d c o n c o mit a nt m e di c ati o n s ............................................................................... 5 0  
8. 8. 2  
C o n c o mit a nt di a b et e s t h er a p y ................................................................................................... ....5 1  
8. 9  
P O S T S T U D Y T R E A T M E N T .......................................................................................................... 5 1  
9  
A S S E S S M E N T O F I N V E S TI G A TI O N A L M E DI CI N A L P R O D U C T .............................................. 5 2  
9. 1  
E F FI C A C Y E N D P OI N T S ............................................................................................................. ..5 2  
9. 1. 1  
Pri m ar y effi c a c y e n d p oi nt...................................................................................................... .........5 2  
9. 1. 2  
S e c o n d ar y effi c a c y e n d p oi nt s ................................................................................................... .....5 2  
9. 1. 3  
Ot h er effi c a c y e n d p oi nt s ....................................................................................................... .........5 2  
9. 1. 4  
A s s e s s m e nt m et h o d s of effi c a c y e n d p oi nt s................................................................................... 5 3  
9. 1. 4. 1  
H e m o gl o bi n A 1 c................................................................................................................. ............5 3  
9. 1. 4. 2  
P o st pr a n di al gl u c o s e a n d mi x e d m e al t ol er a n c e t e st .................................................................... 5 3  
9. 1. 4. 3  
F a sti n g pl a s m a gl u c o s e m e a s ur e m e nt .......................................................................................... 5 4  
9. 1. 4. 4  
B o d y w ei g ht m e a s ur e m e nt ........................................................................................................ ....5 4  
9. 1. 4. 5  
Bl o o d pr e s s ur e e n d p oi nt m e a s ur e m e nt s ....................................................................................... 5 4  
9. 1. 4. 6  
Ki d n e y f u n cti o n p ar a m et er m e a s ur e m e nt...................................................................................... 5 5  
9. 1. 4. 7  
Pr o p orti o n of p ati e nt s r e q uiri n g r e s c u e f or h y p er gl y c e mi a ............................................................ 5 5  
9. 2  
S A F E T Y E N D P OI N T S ............................................................................................................... ....5 5  
9. 2. 1  
A s s e s s m e nt m et h o d s of s af et y e n d p oi nt s ..................................................................................... 5 6  
9. 2. 1. 1  
A d v er s e e v e nt s .............................................................................................................................. 5 6  
9. 2. 1. 2  
H y p o gl y c e mi a................................................................................................................... ..............5 6  
9. 2. 1. 3  
L a b or at or y s af et y v ari a bl e s .................................................................................................... ........5 7  
9. 2. 1. 4  
Vit al si g n s a n d p h y si c al e x a m.................................................................................................. ......5 9  
9. 2. 1. 5  
El e ctr o c ar di o gr a m v ari a bl e s .................................................................................................... ......5 9  
9. 2. 1. 6  
S elf- m o nit ori n g of  bl o o d gl u c o s e....................................................................................................5 9  
9. 2. 1. 7  
Di a b eti c k e t o a ci d o si s .....................................................................................................................6 0  
9. 3  
O T H E R E N D P OI N T S..................................................................................................................... 6 0  
9. 3. 1  
P h ar m a c o ki n eti c s............................................................................................................... ............6 0  
9. 3. 1. 1  
S a m pli n g ti m e ................................................................................................................................6 0  
9. 3. 1. 2  
P h ar m a c o ki n eti c s h a n dli n g pr o c e d ur e........................................................................................... 6 1  
9. 3. 1. 3  
Bi o a n al yti c a l m et h o d ......................................................................................................................6 1  
 
6 1  
9. 5  
A M B U L A T O R Y B L O O D P R E S S U R E M O NI T O RI N G S U B S T U D Y .............................................. 6 2  
 
6 3  
9. 7  
A P P R O P RI A T E N E S S O F  M E A S U R E M E N T S ..............................................................................6 3  
1 0  
S T U D Y P R O C E D U R E S ............................................................................................................... .6 5  
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 2 2 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 2 2 
1 0. 1  
VI SI T S C H E D U L E................................................................................................................. .........6 5  
1 0. 1. 1  
S cr e e ni n g P eri o d............................................................................................................... .............6 5  
1 0. 1. 1. 1  S cr e e ni n g p h a s e ................................................................................................................ ............6 6  
1 0. 1. 1. 2  R u n-i n p h a s e.................................................................................................................................. 6 7  
1 0. 1. 2  
D o u bl e- bli n d r a n d o mi z e d C o r e Tr e at m e nt P eri o d .........................................................................6 8  
1 0. 1. 2. 1  Tr e at m e nt P eri o d ( D a y 1 t o W e e k 2 6) ........................................................................................... 6 8  
1 0. 1. 2. 2  A m b ul at or y bl o o d pr e s s ur e m o nit or pl a c e m e nt o n- sit e Vi sit 7 A a n d 9 A ( W e e k 1 2 a n d W e e k 
2 6) .................................................................................................................................................. 7 2  
1 0. 1. 3  
D o u bl e- bli n d e xt e n si o n p eri o d .................................................................................................. .....7 3  
1 0. 1. 3. 1  O n- sit e vi sit s at W e e k s 3 9, 5 2, a n d 6 5 ( Vi sit s 1 0 t o 1 2) ................................................................ 7 3  
1 0. 1. 3. 2  O n- sit e Vi sit 1 3 at W e e k 7 9 - E n d- of-tr e at m e nt ............................................................................. 7 4  
1 0. 1. 4  
P o st-tr e at m e nt F oll o w- u p p eri o d.................................................................................................... 7 5  
1 0. 1. 4. 1  O n- sit e f oll o w- u p Vi sit 1 4 ( W e e k 8 2).............................................................................................. 7 5  
1 0. 2  
D E FI NI TI O N O F S O U R C E D A T A.................................................................................................. 7 6  
1 0. 2. 1  
S o ur c e d at a t o b e f o u n d i n p ati e nt ’ s fil e.........................................................................................7 6  
1 0. 2. 2  
S o ur c e d at a v erifi c ati o n r e q u ir e m e nt s f or s cre e n f ail ur e s ............................................................. 7 7  
1 0. 3  
H A N D LI N G O F P A TI E N T T E M P O R A R Y O R P E R M A N E N T T R E A T M E N T 
DI S C O N TI N U A TI O N A N D O F P A TI E N T S T U D Y DI S C O N TI N U A TI O N....................................... 7 7  
1 0. 3. 1  
T e m p or ar y tr e at m e nt di s c o nti n u ati o n wit h  i n v e sti g ati o n al me di ci n al pr o d u ct( s) ........................... 7 7  
1 0. 3. 2  
P er m a n e nt tr e at m e nt di s c o nti n u ati o n wit h i n v e sti g ati o n al me di ci n al pr o d u ct( s) ........................... 7 8  
1 0. 3. 3  
Li st of crit eri a f or p er m a n e nt  tr e at m e nt di s c o nti n u ati o n.................................................................7 8  
1 0. 3. 4  
H a n dli n g of p ati e nt s aft er p er m a n e nt tr e at m e nt di s c o nti n u ati o n ................................................... 7 9  
1 0. 3. 5  
Pr o c e d ur e a n d c o n s e q u e n c e f or p ati e nt wit h dr a w al fr o m st u d y.................................................... 7 9  
1 0. 4  
O B LI G A TI O N O F T H E I N V E S TI G A T O R R E G A R DI N G S A F E T Y R E P O R TI N G .......................... 8 0  
1 0. 4. 1  
D efi niti o n s of a d v er s e e v e nt s.................................................................................................. .......8 0  
1 0. 4. 1. 1  A d v er s e e v e nt ................................................................................................................................ 8 0  
1 0. 4. 1. 2  S eri o u s a d v er s e e v e nt ................................................................................................................... 8 0  
1 0. 4. 1. 3  A d v er s e e v e nt of s p e ci al i nt er e st .............................................................................................. .....8 1  
1 0. 4. 1. 4  E v e nt s of s p e c i al i nt er e st ...............................................................................................................8 2  
1 0. 4. 2  
G e n er al g ui d eli n e s f or r e p orti n g a d v e r s e e v e nt s ...........................................................................8 3  
1 0. 4. 3  
I n str u cti o n s f or r e p orti n g s eri o u s a d v er s e e v e nt s ..........................................................................8 3  
1 0. 4. 4  
G ui d eli n e s f or r e p orti n g a d v er s e e v e nt s of s p e ci al i nt er e st ........................................................... 8 4  
1 0. 4. 5  
G ui d eli n e s f or r e p orti n g e v e nt s of s p e ci a l i nt er e st.........................................................................8 4  
1 0. 4. 6  
G ui d eli n e s f or m a n a g e m e nt of s p e cif i c l a b or at or y a b n or m aliti e s .................................................. 8 4  
1 0. 5  
O B LI G A TI O N S O F T H E S P O N S O R ............................................................................................. 8 4  
1 0. 6  
S A F E T Y I N S T R U C TI O N S ............................................................................................................ .8 5  
1 0. 6. 1  
H y p o gl y c e mi a................................................................................................................... ..............8 5  
1 0. 7  
A D V E R S E E V E N T S M O NI T O RI N G .............................................................................................. 8 7  
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 2 3 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 2 3 
1 1  
S T A TI S TI C A L C O N SI D E R A TI O N S .............................................................................................. 8 8  
1 1. 1  
D E T E R MI N A TI O N O F S A M P L E SI Z E........................................................................................... 8 8  
1 1. 2  
DI S P O SI TI O N O F P A TI E N T S ....................................................................................................... 8 8  
1 1. 3  
A N A L Y SI S P O P U L A TI O N S........................................................................................................... 8 9  
1 1. 3. 1  
Effi c a c y p o p ul ati o n s ........................................................................................................... ............8 9  
1 1. 3. 1. 1  I nt e nt-t o-tr e at p o p ul ati o n ................................................................................................................8 9  
1 1. 3. 2  
S af et y p o p ul ati o n .............................................................................................................. .............8 9  
1 1. 4  
S T A TI S TI C A L M E T H O D S ............................................................................................................ .9 0  
1 1. 4. 1  
E xt e nt of st u d y tr e at m e nt  e x p o s ur e a n d c o m pli a n c e.....................................................................9 0  
1 1. 4. 1. 1  E xt e nt of i n v e sti g ati o n al m e di ci n al pr o d u ct e x p o s ur e.................................................................... 9 0  
1 1. 4. 1. 2  C o m pli a n c e ..................................................................................................................... ...............9 1  
1 1. 4. 2  
A n al y s e s of effi c a c y e n d p oi nt s................................................................................................. ......9 1  
1 1. 4. 2. 1  A n al y si s of pri m ar y effi c a c y e n d p oi nt.......................................................................................... ...9 1  
1 1. 4. 2. 2  A n al y s e s of s e c o n d ar y effi c a c y e n d p oi nt s ..................................................................................... 9 2  
1 1. 4. 2. 3  A n al y s e s of ot h er effi c a c y e n d p oi nt s ........................................................................................... ..9 3  
1 1. 4. 2. 4  A n al y si s of a m b ul at or y bl o o d pr e s s ur e m o nit ori n g s u b st u d y e n d p oi nt s........................................ 9 3  
1 1. 4. 2. 5  M ulti pli cit y c o n si d er ati o n s .................................................................................................... ..........9 3  
1 1. 4. 3  
A n al y s e s of s af et y d at a ........................................................................................................ ..........9 4  
1 1. 4. 3. 1  A n al y si s of a d v er s e e v e nt s ..................................................................................................... .......9 4  
1 1. 4. 3. 2  A n al y s e s of h y p o gl y c e mi a ....................................................................................................... ......9 6  
1 1. 4. 3. 3  A n al y s e s of a d v er s e e v e nt s of s p e ci a l i nt er e st..............................................................................9 6  
1 1. 4. 3. 4  A n al y s e s of e v e nt s of s p e ci al i nt er e st......................................................................................... ...9 6  
1 1. 4. 3. 5  A n al y s e s of l a b or at or y v ari a bl e s ............................................................................................... .....9 6  
1 1. 4. 3. 6  A n al y s e s of vit a l si g n v ari a bl e s ......................................................................................................9 6  
1 1. 4. 3. 7  A n al y s e s of 1 2 l e a d E C G st at u s ................................................................................................. ...9 7  
1 1. 4. 4  
A n al y s e s of p h ar m a c o ki n eti c v ari a bl e s.......................................................................................... 9 7  
1 1. 5  
I N T E RI M A N A L Y SI S......................................................................................................................9 7  
1 2  
E T HI C A L A N D R E G U L A T O R Y C O N SI D E R A TI O N S................................................................... 9 8  
1 2. 1  
E T HI C A L A N D R E G U L A T O R Y S T A N D A R D S .............................................................................. 9 8  
1 2. 2  
I N F O R M E D C O N S E N T .................................................................................................................9 8  
1 2. 3  
H E A L T H A U T H O RI TI E S A N D I N S TI T U TI O N A L R E VI E W B O A R D/I N D E P E N D E N T 
E T HI C S C O M MI T T E E (I R B/I E C)................................................................................................... 9 8  
1 3  
S T U D Y M O NI T O RI N G............................................................................................................... ..1 0 0  
1 3. 1  
R E S P O N SI BI LI TI E S O F T H E I N V E S T I G A T O R..........................................................................1 0 0  
1 3. 2  
R E S P O N SI BI LI TI E S O F T H E S P O N S O R O R S E R VI C E  P R O VI D E R .......................................1 0 0  
1 3. 3  
S O U R C E D O C U M E N T R E Q UI R E M E N T S.................................................................................. 1 0 0  
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 2 4 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 2 4 
1 3. 4  
U S E A N D C O M P L E TI O N O F C A S E R E P O R T F O R M S ( C R F S) A N D A D DI TI O N A L 
R E Q U E S T .................................................................................................................................... 1 0 1  
1 3. 5  
U S E O F C O M P U T E RI Z E D S Y S T E M S........................................................................................ 1 0 1  
1 4  
A D DI TI O N A L R E Q UI R E M E N T S................................................................................................. 1 0 2  
1 4. 1  
C U R RI C U L U M VI T A E............................................................................................................... ...1 0 2  
1 4. 2  
R E C O R D R E T E N TI O N I N S T U D Y SI T E S .................................................................................. 1 0 2  
1 4. 3  
C O N FI D E N TI A LI T Y ..................................................................................................................... 1 0 2  
1 4. 4  
P R O P E R T Y RI G H T S................................................................................................................... 1 0 3  
1 4. 5  
D A T A P R O T E C TI O N ................................................................................................................ ...1 0 3  
1 4. 6  
I N S U R A N C E C O M P E N S A TI O N..................................................................................................1 0 4  
1 4. 7  
S P O N S O R A U DI T S A N D I N S P E C TI O N S B Y R E G U L A T O R Y A G E N CI E S ............................... 1 0 4  
1 4. 8  
P R E M A T U R E DI S C O N TI N U A TI O N O F T H E S T U D Y O R P R E M A T U R E C L O S E- O U T O F 
A SI T E ......................................................................................................................... .................1 0 4  
1 4. 8. 1  
B y t h e S p o n s or................................................................................................................. ............1 0 4  
1 4. 8. 2  
B y t h e I n v e sti g at or ............................................................................................................ ...........1 0 5  
1 4. 9  
C LI NI C A L T RI A L R E S U L T S ........................................................................................................ 1 0 5  
1 4. 1 0  
P U B LI C A TI O N S A N D C O M M U NI C A TI O N S ............................................................................... 1 0 5  
1 5  
C LI NI C A L T RI A L P R O T O C O L A M E N D M E N T S ........................................................................ 1 0 7  
1 6  
BI B LI O G R A P HI C R E F E R E N C E S............................................................................................... 1 0 8  
1 7  
A P P E N DI C E S.............................................................................................................................. 1 1 0  
A P P E N DI X A  G UI D A N C E O N C O N T R A C E P TI V E M E T H O D S A N D C O L L E C TI O N O F 
P R E G N A N C Y I N F O R M A TI O N .................................................................................................... 1 1 1  
A P P E N DI X B  A M B U L A T O R Y B L O O D P R E S S U R E M O NI T O RI N G S U B S T U D Y .................................. 1 1 4  
A P P E N DI X C  T W O- H O U R S T A N D A R DI Z E D MI X E D M E A L .................................................................. 1 1 7  
A P P E N DI X D  R E C O M M E N D A TI O N S O N B A SI C G E NI T O U RI N A R Y H Y GI E N E, M AI N T AI NI N G 
H Y D R A TI O N A N D R E C O G NI ZI N G DI A B E TI C K E T O A CI D O SI S............................................... 1 1 9  
A P P E N DI X E  M E A S U R E M E N T O F B L O O D P R E S S U R E A N D P U L S E R A T E ...................................... 1 2 2  
A P P E N DI X F  G E N E R A L G UI D A N C E F O R T H E F O L L O W- U P O F L A B O R A T O R Y 
A B N O R M A LI TI E S B Y S A N O FI.................................................................................................... 1 2 3  
 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 2 5 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 2 5 
2. 1  
LI S T O F T A B L E S 
T a bl e 1 - S u m m ar y of i n v e sti g ati o n al m e di ci n al pr o d u ct s........................................................................ .....4 4  
T a bl e 2 - S er u m c h e mi str y p ar a m et er s ........................................................................................... ..............5 7  
T a bl e 3 - S a m pl e s i d e ntifi cati o n ............................................................................................... .....................6 1  
 
2. 2  
LI S T O F FI G U R E S 
Fi g ur e 1 - H y p o gl y c e mi a cl a s si fi c ati o n i n Stu d y E F C 1 4 8 3 4....................................................................... ...8 6  
 
 
 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 2 6 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 2 6 
3  
LI S T O F A B B R E VI A TI O N S 
 
A B P M:  
a m b ulat or y bl o o d press ure m o nit ori n g 
A C R:
 al b u mi n-creati ni ne
 
rati o
 
A E:
 a d verse
 
e ve nt
 
A E SI:  
a d verse e ve nt of s p ecial i nterest 
A L T:
 ala ni ne
 
a mi n otra nsf eras e
 
A N C O V A:  
A nal ysis of C o varia nce 
A S T:
 as partate
 
a mi n otra nsferas e
 
B MI:  
b o d y mass i n de x 
B P:
 bl o o d
 
press ure
 
C E C:  
Cli nical E n d p oi nt C o m mittee 
CI:
 c o nfi de nce
 
i nter val
 
C R F:  
case r e p ort f or m 
C R O:  
c o ntract r esearc h or ga nizati o n 
C S R:  
cli nical st u d y r e p ort 
C V:
 car di o vas c ular
 
D B P:  
diast olic bl o o d press ure 
DI LI:  
dr u g-i n d uce d li ver i nj uri es 
D K A:
 dia betic
 
ket oaci d osis
 
D M C:  
Data M o nit ori n g C o m mittee 
D R F:  
Discre pa n c y Res ol uti o n F or m 
E C G:
 electr ocar di o gr a m
 
e- C R F:  
electr o nic case re p ort f or m 
e G F R:  
esti mate d gl o mer ular filtrati o n rate 
E M A:  
E ur o pea n Me dici nes A ge nc y 
E O SI:  
e ve nts of s peci al i nterest 
E O T:
 E n d- of- Tr eat me nt
 
F D A:  
F o o d a n d Dr u g A d mi nistrati o n 
F P G:
 fasti n g
 
plas ma
 
gl u c ose
 
F S H:  
f ollicle sti m ulati n g h or m o ne 
G C P:  
G o o d cli nical practice 
G C R:
 gl uc ose-cr eati ni ne
 
rati o
 
GI:
 gastr oi ntesti nal
 
G L P- 1:
 gl uca g o n-li ke
 
pe pti de- 1
 
H b A 1c:
 he m o gl o bi n
 
A 1c
 
H L G T:  
hi g h-le v el gr o u p ter m 
H L T:  
hi g h le vel ter m 
H R T:  
h or m o ne re place me nt t hera p y 
I B:
 I n v esti gat or's
 
Br oc h ure
 
I C F:  
i nf or me d c o nse nt f or m 
I C H:  
I nter nati o nal C o u ncil f or Har m o nisati o n 
I E C:  
i n de pe n de nt et hics c o m mittee 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 2 7 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 2 7 
I M P:
 I n v esti gati o nal me dici nal pr o d uct 
I R B:  
i nstit uti o nal re vie w b oar d 
I R T:  
I nteracti ve Res p o nse Tec h n ol o g y 
I T T:
 i nte nt-t o-treat
 
M A C E:  
maj or a d vers e car di o vasc ular e ve nts 
MI:
 m y ocar dial
 
i nfarcti o n
 
M M:
 mi x e d
 
meal
 
M M T T:  
mi x e d meal t olera nce test 
NI M P:
 n o ni n vesti gati o na l me dici nal pr o d uct 
O C:
 o bser ve d
 
cases
 
P C S A:
 p ote ntiall y
 
cli nicall y  si g nifica nt a b n or malit y 
P D:
 p har mac o d y n a mic
 
P- g p:
 P- gl yc o pr ot ei n
 
PI:
 Pri nci pal
 
I n v esti gat or
 
P K:
 p har mac o ki netic
 
P P G:
 p ost pra n dial
 
gl u c ose
 
P T:
 preferre d
 
t er m
 
P Y Y:
 pe pti de
 
Y Y
 
S A E:  
seri o us a d vers e e v e nt 
S A P:  
statistical a nal ysis pla n 
S B P:  
s yst olic bl o o d press ure 
S C:
 Steeri n g
 
C o m mittee
 
S D:
 sta n dar d
 
de viati o n
 
S E:
 sta n dar d
 
err or
 
S G L T:
 s o di u m- gl uc ose
 
c o-tra ns p orter
 
S G L T 1:  
s o di u m- gl uc ose c o ntra ns p orter t y pe 1 
S G L T 2:  
s o di u m- gl uc ose c otra ns p orter t y pe 2 
S M B G:  
self- m o nit ori n g of bl o o d gl uc ose 
S O C:  
s yste m or ga n class 
S U S A R:  
s us pecte d u ne x pecte d seri o us a d verse reacti o n 
T 1 D:  
t y pe 1 dia b etes mellit us 
T 2 D:  
t y pe 2 dia b etes mellit us 
T E A E:  
treat me nt-e mer ge nt a d v erse e ve nts 
T G:
 tri gl yceri des
 
U G E:  
uri nar y gl uc ose e x creti o n 
U L N:  
u p per li mit of n or mal 
U S:
 U nite d
 
States
 
W O C B P:  
w o me n of c hil d- beari n g p ote ntial 
 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 2 8 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 2 8 
4  
I N T R O D U C TI O N A N D R A TI O N A L E 
4. 1  
B A C K G R O U N D: S O T A G LI F L O ZI N A N D DI S E A S E 
S ota glifl ozi n is a d ual i n hi bit or of t he s o di u m- g l u c ose c otra ns p orters t y pe 1 a n d 2 ( S G L T 1 a n d 
S G L T 2) b ei n g de vel o pe d f or use i n t y pe 2 dia bet es mellit us ( T 2 D), a meta b olic dis or der 
c haracterize d b y h y per gl yce mia t hat res ults fr o m a c o m bi nati o n of i ncreas e d i ns uli n resista nce 
a n d beta cell d ysf u ncti o n. T he mic r o vasc ul ar c o m plicati o ns of dia betes are well k n o w n a n d ca n 
res ult i n i m paire d re n al f u nctio n, reti n o pat h y a n d ne ur o pat h y. Ot her c o m or bi dities t hat are 
fre q ue ntl y ass o ciate d wit h dia betes are h y pert e nsi o n, o besit y, a n d car di o v asc ular ( C V) disease. 
Rece ntl y, t h e Ce nters f or Disease C o ntr ol a n d Pre ve nti o n releas e d a re p ort stati n g t hat if c urre nt 
tre n ds c o nti n ue, 1 i n 3 A merica ns will ha ve di a betes b y t he year 2 0 5 0. Acc or di n g t o t he m ost 
rece nt I nter nati o nal Di a b etes Fe d er ati o n Dia betes Atlas, t he esti mates i n 2 0 1 5 were t hat 1 i n 
1 1 a d ults ha ve dia betes, w hic h mea ns 4 1 5 milli o n pe o ple; esti mate d t o rise t o 6 4 2 milli o n b y 
2 0 4 0 ( 2 ). 
I n 2 0 1 0, 3 3 milli o n pe o ple i n t he E ur o pea n U ni o n had dia betes, 9 % of t he a d ult p o p ulati o n. T his 
n u m ber is pr ojecte d t o i n creas e t o 3 8 milli o n b y 2 0 3 0 ( 3 ). W hile t hese n u m bers i ncl u de b ot h 
pe o ple wit h T 2 D a n d t y p e 1 dia betes ( T 1 D), o ver 9 0 %  of a d ults wit h dia betes ha ve T 2 D. Di a betes 
is a m o n g t he lea di n g ca uses of deat h b y disease a n d is a lea di n g ca us e of h eart diseas e, str o ke, 
bli n d ness, ki d ne y diseas e, a n d a m p utati o n ( 2 , 3 ). Des pite t he fact t hat t he p o p ulati o n of pe o ple 
wit h dia betes is gr o wi n g, n o ne of t he c urre nt t her a pies is c urati ve a n d t he res ults of treat me nt are 
varia ble. 
Alt h o u g h lifest yle c h a n ges, i ncl u di n g diet, e x er cise, a n d e d u cati o n, are val u a ble c o m p o ne nts of 
dia betes treat me nt, t he vast maj orit y of pe o pl e wit h T 2 D re q uire p har mac ol o gical t hera p y t o 
c o ntr ol t he disease. I n t he U nite d States ( U S) a n d E ur o pe, metf or mi n is t he sta n dar d first-li ne 
t hera p y i n t he a bs e nce of a n y c o ntrai n dicati o ns or t olera bilit y iss ues as per g ui da n ce fr o m t he 
A merica n Ass o ciati o n of Dia betes ( 4 ).  
Des pite t he n u mer o us tr eat me nt o pti o ns a vaila ble, m o n ot hera p y fails i n ma n y patie nts as b eta-cell 
f u ncti o n c o nti n ues t o det eri orate l ea di n g t o pr o gressi vel y i ncreasi n g h y per gl yce mia. A g gressi ve 
gl yce mic c o ntr ol wit h t he c urre ntl y a vaila ble a ge nts ofte n lea ds t o si de effects, m ost n ota bl y 
wei g ht gai n a n d a n i ncrease d fr e q ue nc y of h y p o gl yce mia. T hes e c o ncer ns e m p hasize t he nee d t o 
de vel o p ne w a ge nts t hat effecti vel y a n d sa fel y l o wer gl uc ose i n dia b etic p atie nts. 
I n p atie nts wit h dia betes, it is desira ble t o mai ntai n bl o o d gl uc ose i n t he n or mal ra n ge wit h o ut 
e x ha usti n g t he a bilit y of t he pa ncr eatic b eta-cells t o pr o d uce i ns uli n. Gl uc ose is tra ns p orte d acr oss 
t he cell me m bra n e b y 2 differe nt t y pes of gl uc ose tra ns p orters: gl uc os e-facilitate d tra ns p orters a n d 
S G L T pr ot ei ns ( 5 ). I n t he ki d ne y, after bl o o d is filt ere d b y t he gl o mer ul us, gl uc ose passes i nt o t he 
uri ne, b ut 9 9 % is rea bs or be d, pri maril y via S G L T 2, w hic h is res p o nsi ble f or 9 0 % of gl uc ose 
rea bs or pti o n, w hile 1 0 % is rea bs or be d b y S G L T 1. W he n f u ncti o nal S G L T 2 is lac ki n g i n h u ma ns, 
a si g nifica nt a m o u nt of gl uc ose re mai ns i n  t he uri ne a n d is re m o ve d fr o m t he b o d y (6 ). T his wa y 
of re d uci n g bl o o d gl uc os e is n ot a n i ns uli n- de pe n de nt mec ha nis m; t heref ore h y p er gl yce mia ma y 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 2 9 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 2 9 
be re d uce d w hile t he p a n creas is s pare d fr o m a n i ncreas e d de ma n d f or i ns uli n pr o d ucti o n t hat is 
ca use d b y h y p er gl yce mia. Si nce o besit y is a si g nifica nt c o m or bi dit y i n T 2 D M, a n d i ns uli n 
resista nce is i ncr eas e d i n o besit y, t he cal oric l oss fr o m gl uc os e i n t he uri ne ma y re prese nt a n 
a d diti o nal be nefit res ulti n g i n decrease d w ei g ht, w hic h s h o ul d res ult i n decreas e d i ns uli n 
resista nce (6 ).  
T he S G L T 1 is e x presse d pre d o mi na ntl y i n t he gast r oi ntesti nal ( GI) tract; S G L T 1 is res p o nsi ble 
f or t he maj orit y of gl uc os e a bs or pti o n b y t he s mall i ntesti ne (7 ). I n hi biti o n of S G L T 1 i n t he GI 
tract pre v e nts gl u c ose fr o m bei n g a bs or be d. A d diti o nall y, t here is acc u m ulati n g e vi de n ce t hat 
S G L T 1 i n hi biti o n sti m ulates secr eti o n of gl uca g o n-li ke pe pti de- 1 ( G L P- 1) a n d pe pti de Y Y 
( P Y Y), g ut h or m o nes i n v ol ve d i n pa ncreatic beta-cell f u ncti o n a n d a p p etite c o ntr ol, res pecti vel y. 
Re d uce d gl uc ose a bs or pti o n i n t he pr o xi mal i ntesti ne lea ds t o m ore gl uc ose bei n g d eli vere d 
distall y, w hic h all o ws L cells i n b ot h t he ile u m a n d t he c ol o n t o se nse gl uc ose a n d its b y pr o d ucts, 
a n d as a r es ult, t he y s ecr ete G L P- 1 a n d P Y Y. A lt h o u g h a c o m plete lac k of f u ncti o nal S G L T 1 ma y 
be ass ociate d wit h s y m pt o ms of gl uc os e a n d galact ose mala bs or pti o n ( 8 ), p har mac ol o gic 
i n hi biti o n of S G L T 1 b y s ota glifl ozi n has n ot pro d uce d t hese effects i n precli nical m o dels or 
patie nts wit h T 2 D. Selecti ve i n hi bit ors of t he S G L T 1 tra ns p orter are i n earl y sta ges of 
de vel o p me nt. 
E xte nsi ve cli nical st u dies c o n d ucte d f or selecti ve S G L T 2 i n hi bit ors ha ve esta blis he d t his class as 
effecti ve a ge nts f or t he treat me nt of T 2 D ( 9 , 1 0 , 1 1 ) a n d ha ve l e d t o a p pr o v als b y t he U S F o o d 
a n d Dr u g A d mi nistrati o n ( F D A) a n d t he E ur o p ea n Me dici nes A ge n c y ( E M A). St u dies wit h 
s ota glifl ozi n, a p ote nt, d ual i n hi bit or of S G L T 2 a n d S G L T 1, ha v e s h o w n t h at t his a ge nt pr o d uces 
si g nifica nt gl uc os uria i n precli nical a ni mal mo dels, healt h y h u ma n v ol u nteers, a n d patie nts wit h 
T 2 D. Si n gle a n d m ulti ple- d ose a d mi nistrati o n of s ota glifl ozi n t o healt h y h u ma n patie nts has 
res ulte d i n d ose- de p e n de nt i ncreases i n gl uc os uri a. M ulti ple- d ose ( 2 8- da y) a d mi nistrati o n i n 
dia betic patie nts pr o d uce d i m pr o ve me nts i n se veral meta b olic para meters, i ncl u di n g uri nar y 
gl uc ose e x creti o n ( U G E), fasti n g plas ma gl u c ose ( F P G), he m o gl o bi n A 1c ( H b A 1c), G L P- 1, a n d 
P Y Y. T hese data s u g gest t hat s ota glifl ozi n s h o ul d be  of t hera pe utic be n efit t o patie nts wit h T 2 D.  
4. 2  
C LI NI C A L T RI A L S O F S O T A G LI F L O ZI N I N H U M A N S 
A p pr o xi matel y 7 8 0 s u bj ects ( 6 3 9 assi g n e d t o s o ta glifl ozi n a n d 1 4 1 assi g n e d t o place b o) ha v e 
partici pate d i n c o m plete d cli nical st u dies of s ota glifl ozi n. N o si g nifica nt safet y c o ncer ns ha ve 
bee n i de ntifie d i n t he s ot a glifl ozi n dr u g pr o gra m, a n d s ota glifl ozi n has bee n well-t olerate d i n all 
st u dies t o date. Seri o us a d verse e v e nts ( S A Es) a n d disc o nti n uati o ns d ue t o a d verse e ve nts ( A Es) 
ha ve bee n i nfre q u e nt a n d ha ve bee n bala n ce d bet wee n treat me nt a n d c o m parat or gr o u ps. R e p orts 
of treat me nt-e mer ge nt a d verse e v e nts ( T E A E) acr oss all s ota glifl ozi n st u dies f or w hic h d ata are 
a vaila ble w ere ge nerall y bala nce d  b et wee n treat m e nt a n d c o m parat or gr o u ps. T he m ost fre q ue ntl y 
re p orte d T E A Es (≥2. 0 %) were h ea dac he, n a usea, diarr hea, c o nsti pati o n, a n d dizzi ness, all of 
w hic h were re p orte d at a fre q ue n c y greater t h a n  place b o. H o we ver, m ost were des cri be d as mil d 
t o m o derate, a n d m ost res ol ve d s p o nta ne o usl y.  
I n c o m plete d a n d o n g oi n g cli nical trials, n o safet y iss ues i n a d diti o n t o t h ose alrea d y descri be d i n 
t he c urr e nt I n vesti gat or Br oc h ure w ere o bs er ved. I n ge neral, n o si g nifi ca nt i m bala nces of 
S A E/ A Es bet wee n s ota glifl ozi n a n d c o m parat ors were o bs er ve d i n c o m plete d st u dies.  
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 3 0 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 3 0 
C u m ulati vel y, d uri n g t he cli nical trial pr o gra m 8 S A Es were re p orte d b y 6 patie nts ( 4 T 2 D a n d 
2 T 1 D), all of w hic h wer e assesse d as u nrelat e d t o st u d y dr u g; t h ose re p orte d b y 4 T 2 D p atie nts 
w h o recei ve d s ota glifl ozi n i ncl u de d p ul m o nar y e m b olis m, dee p vei n t hr o m b osis, bile d uct st o ne, 
c h ola n gitis a n d l o wer li m b fract ure, w hile a m y o car dial i nfarcti o n ( MI) was e x perie nce d b y a 
patie nt recei vi n g place b o. T w o S A Es of dia betic k et oaci d osis were re p orte d b y 2 T 1 D p atie nts 
recei vi n g 4 0 0 m g o nce d ail y s ota glifl ozi n i n t he P hase 2 T 1 D st u d y L X 4 2 1 1. 1- 2 0 3- TI D M; b ot h 
S A Es were assesse d as d ue t o fail ure  of i ns uli n deli ver y via i ns uli n p u m p. 
A dr u g i nteracti o n st u d y wit h di g o xi n, a se nsiti ve P- gl yc o pr ot ei n ( P- g p) s u bstrate, i n dicate d t hat 
s ota glifl ozi n acts as a w ea k P- g p i n hi bit or.  
M ore i nf or mati o n o n t he safet y of s ota glifl ozi n a n d o n t he cli nical pr o gra m ca n be f o u n d i n t he 
I n v esti gat or Br oc h ur e (I B). 
4. 3  
R A TI O N A L E F O R S E L E C TI O N O F D O S E 
T he pr o p ose d 4 0 0 m g o n ce dail y d ose is base d o n t he res ults of t he P hase 2 b st u d y 
L X 4 2 1 1. 1- 2 0 2- D M. I n t his st u d y d os es of 7 5 m g o nce dail y, 2 0 0 m g o nce d ail y, 2 0 0 m g t wice 
dail y, a n d 4 0 0 m g o n ce d ail y s ota glifl ozi n were  teste d o ver a 1 2- wee k, d o u ble- bli n d peri o d. T he 
4 0 0 m g o nce dail y d ose was c h ose n f or f urt h er e v al uati o n base d o n its H b A 1c l o weri n g effect a n d 
t he o verall safet y a n d t ol era bilit y o bs er ve d at t his d ose. At 1 2 wee ks, t he 4 0 0 m g d ose l o w ere d 
H b A 1c b y a mea n of 0. 9 3 %, w hile place b o l o w ere d H b A 1c b y a mea n of 0. 1 4 %. L o wer d os es 
were less eff ecti ve t ha n t he 4 0 0 m g d os e a n d di d n ot ha ve a n y a d v a nta ges i n safet y or t olera bilit y. 
T he o ver all i nci de nce of A Es i n patie nts recei vi n g 4 0 0 m g o nce dail y was si milar t o t hat see n wit h 
place b o. 
I n h ealt h y s u bjects s ota glifl ozi n was well-t olerate d f oll o wi n g si n g le d oses u p t o 2 0 0 0 m g, a n d i n 
m ulti ple d oses u p t o 8 0 0 m g o ver 1 0 da ys. F urt her m or e, si n gle d os es of s ot a glifl ozi n ( 8 0 0 m g a n d 
2 0 0 0 m g) w ere well-t oler ate d a n d di d n ot pr ol o n g t he Q T i nter val. A d diti o n all y, e v al uati o n of 
meta b olites i n uri ne a n d plas ma of healt h y s u bjects res ulte d i n n o safet y c o ncer ns f oll o wi n g si n gle 
d oses of 4 0 0 m g s ota glifl ozi n. Si n gle d oses of  4 0 0 m g i n c o m bi nati o n wit h sita gli pti n, a n d 
m ulti ple d oses u p t o 4 0 0 m g i n c o m bi nati o n wit h metf or mi n o ver 1 2 wee ks were als o 
well-t olerate d i n p atie nts wit h T 2 D. 
4. 4  
R A TI O N A L E F O R S T U D Y D E SI G N A N D C O N T R O L G R O U P S 
T his st u d y is desi g n e d t o de m o nstrate t he efficac y  a n d safet y of s ot a glifl ozi n w he n use d as a d d- o n 
t hera p y t o metf or mi n i n patie nts wit h T 2 D w h o ha ve i na de q u ate gl yce mic c o ntr ol. S ota glifl ozi n 
pl us metf or mi n will be c o m pare d t o place b o pl us metf or mi n. Bas e d o n t he st u d y desi g n, t he 
pr ot oc ol sti p ulates t hat patie nt s be pr o vi de d a nti di a betic a ge nt resc u e t hera p y acc or di n g t o a 
pre defi n e d al g orit h m. Safet y, t olera bilit y, p h ar mac o ki netic ( P K) a n d p h ar mac o d y na mic ( P D) 
effects of s ota glifl ozi n are s u p p orte d b y P hase 1 a n d P hase 2 st u dies a n d t o xic ol o g y dat a i n rats u p 
t o 2 6 wee ks a n d d o gs u p t o 3 9 wee ks as w ell as 2- year carci n o ge nicit y d ata i n rats. 
T o ac hie ve b ala nce d ra n d o miza ti o n f or assess me nt of t he pri mar y e n d p oi nt, ra n d o mizati o n will be 
stratifie d base d o n pree xisti n g meta b olic c o ntr ol ( Scree ni n g H b A 1 c ≤8. 0 % vers us > 8. 0 %). 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 3 1 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 3 1 
A n ot her stratificati o n fact or (s yst olic bl o o d press ure  [ S B P] < 1 3 0 m m H g vers us ≥1 3 0 m m H g) h as 
bee n a d d e d t o e ns ure b al a nce i n r a n d o mizati o n f o r a sec o n d ar y e n d p oi nt (c ha n ge fr o m Bas eli ne t o 
1 2- wee ks i n S B P f or pati e nts wit h baseli ne S B P ≥1 3 0 m m H g). 
A place b o c o ntr ol will be use d t o all o w f or a n u n bi ase d assess me nt of treat me nt effects a n d safet y 
data. Bias will be mi ni mize d b y ra n d o mizi n g t he p atie nts t o treat me nt gr o u ps, bli n di n g t he 
patie nts, t he I n vesti gat ors, a n d t he S p o ns or t o t he treat me nt all ocati o ns, a n d b y a dj u dicati n g t h e 
e n d p oi nts i n a bli n de d fas hi o n. 
A parallel- gr o u p, ra n d o mize d place b o c o ntr olle d d esi g n w as selecte d be ca use trial partici pa nts are 
e x p ose d t o a si n gle treat me nt a n d assi g n m e nt t o t hat treat me nt is base d s ol el y o n c ha nce.  T his 
desi g n is fr ee of t he li mitati o ns of c o m peti n g d esi g ns s uc h as cr oss o ver i n w hic h t here ma y b e a 
carr y o v er of eff ect fr o m o ne treat me nt t o t he sec o n d treat me nt. Alt h o u g h t his carr y o ver effect ca n 
be mi ni mize d wit h a was h o ut peri o d, it is p ossi ble t h at s o me l o n ger ter m effects ma y persist.  
W hile t he sa m ple size of t he pa rallel gr o u p d esi g n is lar ger t o acc o u nt f or m ore vari a bilit y w he n 
partici pa nts ca n n ot ser ve as t heir o w n c o ntr ol,  t he a b o ve- me nti o ne d li mitati o ns of t he cr oss o ver 
desi g n ha ve le d t he ra n d o mize d c o ntr olle d trial desi g n t o be t he sta n d ar d f or t hera pe utic 
c o nfir mat or y trials f or re g ulat or y a p pr o val s uc h as t his trial. 
4. 5  
R A TI O N A L E F O R A M B U L A T O R Y B L O O D P R E S S U R E M O NI T O RI N G S U B S T U D Y 
Data fr o m a P hase 2 trial of s ota glifl ozi n ( L X 4 2 1 1. 1- 2 0 2) s u g gest t hat s ota glifl ozi n re d uce d b ot h 
S B P a n d diast olic bl o o d press ure ( D B P) i n p atie nts wit h ele vate d S B P a n d D B P at baseli ne b ut 
n ot n or m ote nsi ve patie nts. I n or de r t o s yste maticall y assess t he S B P a n d D B P l o weri n g efficac y 
of s ota glifl ozi n, b ot h sitti n g bl o o d pr ess ure at  st u d y visits a n d a m b ulat or y bl o o d press ure 
m o nit ori n g ( A B P M) will be meas ur e d. A m b ulat or y bl o o d press ure m o nit ori n g is m ore cl osel y 
c orrel ate d wit h mar kers of or ga n da m a ge, a n d is a m ore se nsiti ve pre dict or of C V o utc o mes ( 1 2 ). 
It als o p er mits assess me nt of nig htti me a n d da yti m e bl o o d press ure ( 1 2 ), a n d has bee n s h o w n t o 
re d uce t h e “ w hite c oat” effect see n wit h sitti n g bl o o d press ure meas ure m e nts. 
4. 6  
B E N E FI T/ RI S K O F S O T A G LI F L O ZI N 
S ota glifl ozi n is c urre ntl y bei n g i n vesti gate d as  a n a dj u nct t o diet a n d e x ercise t o i m pr o ve 
gl yce mic c o ntr ol i n a d ults wit h T 2 D. T he st u d y pr o gra m will als o pr o vi de efficac y a n d safet y data 
f or s ota glifl ozi n i n c o m bi nati o n wit h ot her a nti dia betic me dicati o ns. I n a d diti o n t he st u d y pr o gra m 
will e val uate cli nical o ut c o mes i n patie nts wit h hi g h C V ris k a n d i n p atie nts wit h re nal 
i m pair me nt. T he use of s ota glifl ozi n i n t he treat me nt of T 1 D is als o bei n g st u die d i n a se parat e 
de vel o p me nt pr o gr a m. 
S ota glifl ozi n ma y be n efit a wi de vari et y of dia beti c patie nts base d o n m ulti ple p ote ntial be nefici al 
effects of d ual S G L T 2/ S G L T 1 i n hi biti o n, a n d its i ns uli n-i n de pe n de nt mec ha nis m of acti o n. 
I m pr o v e me nts i n H b A 1c, F P G, a n d p ost pra n dial gl uc ose ( P P G) were o bser ve d wit h s ota glifl ozi n 
i n m ulti ple st u dies. As a ntici pate d fr o m t he mec h a nis m of acti o n, treat me nt wit h s ota glifl ozi n 
res ulte d i n i ncrease d U G E (fr o m i n hi biti o n of S G L T 2) as well as i ncrease d i ncreti n le vels (fr o m 
i n hi biti o n of S G L T 1). I n a d diti o n, t he i m pr o ve ments i n b o d y wei g ht, bl o o d press ure ( B P), a n d 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 3 2 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 3 2 
tri gl yceri des ( T G) o bser v e d wit h s ota glifl ozi n treat me nt ha ve t he p ote ntial t o be nefit patie nts wit h 
dia betes t hr o u g h t heir effects o n c o m m o n dia betic c o m or bi dities. 
O verall, s ota glifl ozi n has bee n well-t olerate d i n all st u dies t o date, wit h t he maj orit y of e ve nts 
assesse d as mil d t o m o dera te; m ost of w hic h res ol ve d s p o nta ne o usl y. Se vere a d vers e e v e nts a n d 
disc o nti n uati o ns d ue t o A Es ha ve bee n li mite d a n d bala nce d b et wee n treat me nt a n d c o m parat or 
gr o u ps. Se v ere h y p o gl yc e mia, ge n ital m yc otic i nfecti o ns, uri nary tract i nfecti o ns, dia betic 
ket oaci d osis ( D K A), v ol u me de ple ti o n wit h seri o us c o nse q ue nce ( ort h ostasis, falls, fract ures), 
se vere di arr h ea, pa n creatitis, b o ne fract ures, ve n o us t hr o m b otic e ve nts, dr u g-i n d uce d li ver i nj uries 
( DI LIs), s e ver e r e nal e ve nts an d mali g na n cies of s pecial i nterest  ( breast, bl a d der, re nal cell, 
Le y di g cell, pa ncreatic, pr ostate , a n d t h yr oi d carci n o ma) are m o nit ore d cl osel y as i d e ntifie d a n d 
p ote ntial ris ks. 
T he i m pr o ve me nt i n gl yc e mic c o ntr ol, t he re d ucti o ns i n wei g ht a n d B P, a n d t he t olera bilit y a n d 
safet y pr ofile of s ota glifl ozin t o date, de m o nstrate a fa v ora b le be n efit-ris k assess me nt f or 
s ota glifl ozi n. 
 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 3 3 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 3 3 
5  
S T U D Y O B J E C TI V E S 
5. 1  
P RI M A R Y  
T he pri mar y o bjecti ve of t his st u d y is t o de m o nstrate t he s u peri orit y of s ota glifl ozi n 4 0 0 m g 
vers us place b o o n H b A 1 c re d ucti o n at Wee k 2 6 i n patie nts wit h T 2 D w h o ha ve i na de q u ate 
gl yce mic c o ntr ol wit h metf or mi n. 
5. 2  
S E C O N D A R Y  
•  T o c o m pare s ota glifl ozi n 4 0 0 m g vers us place b o f or:  
- 
C ha n ge fr o m Baseli ne i n 2- h o ur P P G f oll o wi n g a mi x e d meal ( M M) at Wee k 2 6 
- 
C ha n ge fr o m Baseli ne i n F P G at Wee k 2 6 
- 
C ha n ge fr o m Baseli ne i n b o d y w ei g ht at Wee k 2 6 
- 
C ha n ge fr o m Baseli ne i n S B P at Wee k 1 2 f or patie nts wit h Baseli ne S B P ≥1 3 0 m m H g  
- 
C ha n ge fr o m Baseli ne i n S B P at Wee k 1 2 f or all p atie nts 
- 
Pr o p orti o n of patie nts wit h H b A 1c < 6. 5 %, < 7. 0 % at Wee k 2 6 
•  T o e val uate t he s afet y of s ota glifl ozi n 4 0 0 m g vers us place b o t hr o u g h o ut t h e 7 9- wee k 
trial. 
5. 3  
O T H E R 
•  T o c o m pare s ota glifl ozi n vers us place b o wit h res p ect t o c ha n ge fr o m Baseli ne o n t he 
f oll o wi n g e n d p oi nts: 
- 
Uri ne al b u mi n-creati ni ne rati o ( A C R) 
- 
Uri nar y gl uc os e e x creti o n a n d uri ne gl uc ose-creati ni ne rati o ( G C R) 
- 
Esti mate d gl o mer ular filtrati o n rate (e G F R) 
- 
Re d ucti o n i n b o d y wei g ht b y ≥2 %, ≥5 %, a n d ≥1 0 % 
•  T o c o m pare s ota glifl ozi n vers us place b o f or: 
- 
C ha n ge fr o m Baseli ne i n H b A 1c at Wee k 7 9 
- 
C ha n ge fr o m Baseli ne i n F P G at Wee k 7 9 
- 
C ha n ge fr o m Baseli ne i n S B P at Wee k 2 6 f or all p atie nts a n d f or patie nts wit h 
Baseli ne S B P ≥1 3 0 m m H g 
- 
C ha n ge fr o m Baseli ne i n S B P at Wee k 7 9 f or all p atie nts a n d f or patie nts wit h 
Baseli ne S B P ≥1 3 0 m m H g 
- 
C ha n ge fr o m Baseli ne i n b o d y w ei g ht at Wee k 7 9 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 3 4 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 3 4 
•  T o c o m pare t h e use of resc ue me dicati o ns f or h y p er gl yce mia i n t he s ota glifl ozi n a n d 
place b o tre at me nt gr o u ps 
•  T o assess plas ma c o n ce ntrati o ns of s ota glifl ozi n a n d its 3- O- gl u c ur o ni de m eta b olite. 
5. 4  
A M B U L A T O R Y B L O O D P R E S S U R E M O NI T O RI N G S U B S T U D Y 
T he pri mar y o bjecti ve of t he A B P M s u bst u d y is t o  c o m pare t he effect of s ot a glifl ozi n vers us 
place b o i n a s u bset of p atie nts wit h mea n S B P ≥1 3 0 m m H g at Scree ni n g o n 2 4- h o ur a vera ge S B P 
at Wee k 1 2. 
T he sec o n d ar y o bjecti ves of t he A B P M s u bst u d y are t o c o m pare t he effect of s ota glifl ozi n vers us 
place b o i n a s u bset of p atie nts wit h mea n S B P ≥1 3 0 m m H g at Scree ni n g o n t he f oll o wi n g: 
•  2 4- h o ur a vera ge S B P at Wee k 2 6 
•  2 4- h o ur a vera ge D B P at Wee ks 1 2 a n d 2 6 
•  A vera ge a dj uste d a wa ke ti me bl o o d press ure ( B P) as meas ure d b y S B P a n d D B P at Wee ks 
1 2 a n d 2 6 wit h a dj ust me nt base d o n acti gra p h y 
•  A vera ge a dj uste d slee pi n g ti me B P as m eas ure d b y S B P a n d D B P at Wee ks 1 2 a n d 2 6 
wit h a dj ust me nt base d o n acti gra p h y 
F ull details of t he A B P M s u bst u d y are pr o vi de d i n A p pe n di x B . 
 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 3 5 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 3 5 
6  
S T U D Y D E SI G N 
6. 1  
D E S C RI P TI O N O F T H E S T U D Y 
T his st u d y is a P hase 3, m ultice nter a n d m ulti nati o nal, 1: 1 ra n d o mize d, d o u ble- bli n d, 
place b o- c o ntr olle d, par allel- gr o u p st u d y t hat is a n tici pate d t o e nr oll a p pro xi matel y 5 0 0 p atie nts. 
T he st u d y will c o m prise a Scree ni n g Peri o d c o nsisti n g of a Scree ni n g p has e of u p t o 2 wee ks a n d 
a 2- wee k si n gl e- bli n d R u n-i n p hase, a d o u ble- bli n d C ore Treat me nt Peri o d, a d o u ble- bli n d 
E xte nsi o n Peri o d, a n d a F oll o w- u p Peri o d. A d diti o nall y, t here will be a n A B P M s u bst u d y f or a 
s u bset of patie nts wit h mea n Scree ni n g S B P ≥1 3 0 m m H g. Se parate i nf o r m e d c o nse nt will be 
ta ke n bef ore patie nts partici pate i n t he A B P M s u bst u d y. 
T he st u d y d esi g n is pr ese nte d gr a p hicall y at t he e n d of t he s y n o psis. 
6. 1. 1  S cr e e ni n g P eri o d 
6. 1. 1. 1  S cr e e ni n g p h a s e ( Vi sit 1) 
T he Scree ni n g p h ase will last u p t o 2 wee ks. T he p eri o d m ust be l o n g e n o u g h t o c ollect t he data 
re q uire d t o esta blis h w h et her t he patie nt satisfies t he i ncl usi o n/e x cl usi o n criteria. 
Patie nts ta ki n g metf or mi n at a sta ble d osa ge ≥1 5 0 0 m g/ da y f or at least 1 2 wee ks bef ore 
e nr oll me nt will be eli gi bl e f or scree ni n g. 
Patie nts o n metf or mi n at a d ose < 1 5 0 0 m g/ da y at t h e ti me of e nr oll me nt ( m ai ntai ne d f or at least 
1 2 wee ks bef ore e nr oll me nt) ma y be eli gi ble f or s cree ni n g if d o c u me ntati o n of lac k of t olera nce 
of a metf or mi n d ose ≥1 5 0 0 m g/ da y ca n be pr o vi d e d.  
At t he Scree ni n g Visit aft er si g ni n g of t he i nf or me d c o nse nt f or m (I C F), eli gi bilit y criteria will be 
assesse d a n d Scree ni n g assess me nts will be perf or me d. W o me n of c hil d beari n g p ote ntial 
( W O C B P) n ot willi n g t o use hi g hl y effecti ve met h o d(s) of birt h c o ntr ol d uri n g t he st u d y treat me nt 
peri o d a n d t he f oll o w- u p peri o d, or w h o are u n willi n g or  u n a ble t o be teste d f or pre g n a nc y will be 
e x cl u de d fr o m t he st u d y; g ui da n ce o n hi g hl y eff ecti ve c o ntrace pti ve met h o ds a n d c ollecti o n of 
pre g na nc y i nf or mati o n is pr o vi de d i n A p pe n di x A . If a n ot her c o ntrace pti ve met h o d is use d (s uc h 
as a barrier met h o d), it s h o ul d be use d i n c o m bi na ti o n wit h o ne of t he hi g hl y effecti ve met h o ds i n 
A p pe n di x A  (s uc h as a n oral c o ntrace pti ve). 
T he I nteracti ve Res p o nse Tec h n ol o g y (I R T; eit h er I nteracti ve V oice Res p o nse S yste m or 
I nteracti ve We b Res p o nse S yste m) will be c o ntact e d at Visit 1 f or n otificati o n of scree ni n g a n d 
f or patie nt n u m ber all ocati o n. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 3 6 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 3 6 
6. 1. 1. 2  R u n-i n p h a s e ( Vi sit 2) 
T he R u n-i n p hase will last 2 wee ks. Patie nts will be treate d i n a si n gl e- bli n d ma n ner wit h place b o 
( 2 ta blets) o nce d ail y d uri n g t he R u n-i n p hase, st arti n g fr o m Visit 2. Patie nts i ncl u de d i n t he 
A B P M s u bst u d y will als o atte n d Visit 3 A f or place me nt of t he A B P M. 
6. 1. 2  D o u bl e- bli n d C or e Tr e at m e nt P eri o d ( W e e k 0 t o W e e k 2 6) 
Eli gi ble patie nts will be r a n d o mize d o n Da y 1 ( V isit 3). I n or d er t o q ualif y f or ra n d o mizati o n, 
patie nts m ust de m o nstrate c o m plia nce d uri n g t h e si n gle- bli n d place b o R u n-i n p hase base d u p o n 
ta blet c o u nt (≥8 0 %).  
Ra n d o mizati o n will be stratifie d b y: 
•  H b A 1c at Scr ee ni n g ( ≤8. 0 %, > 8. 0 %) 
•  S B P at Scree ni n g ( < 1 3 0 m m H g, ≥1 3 0 m m H g)  
F oll o wi n g ra n d o mizati o n, patie nts will be treate d i n a d o u ble- bli n d ma n ner f or 2 6 wee ks. All 
patie nts will ha ve P P G assesse d f oll o wi n g a M M T T at Wee ks 0 a n d 2 6. A t otal of 5 0 0 patie nts 
≥1 8 years of a ge ( or ≥le gal a ge of maj orit y if great er) will be ra n d o ml y assi g ne d 1: 1 t o t he 
f oll o wi n g 2 treat me nt gr o u ps: 
•  S ota glifl ozi n 4 0 0 m g as t w o 2 0 0 m g ta blets, o nce dail y 
•  Place b o as t w o place b o t a blets (i de ntical t o  s ota glifl ozi n i n a p peara nce), o n ce dail y 
Fasti n g gl uc ose ( plas m a or ser u m), H b A 1 c, a n d P P G will be mas ke d t o st u d y sites a n d p atie nts 
after r a n d o mizati o n u ntil st u d y e n d. T o pre ve nt pa rtial u n bli n di n g, U G E a nd G C R res ults will be 
mas ke d t o i n vesti gati o nal sites a n d patie nts, a n d t he ce ntral la b orat or y uri ne di pstic k will n ot 
i ncl u de t he meas ur e me nt of uri ne gl uc ose. 
If a patie nt disc o nti n ues treat ment wit h i n vesti gati o nal me dici nal pr o d uct (I M P) earl y d uri n g t he 
2 6- wee k C or e Treat me nt Peri o d, t h e patie nt will ha ve a Pre m at ure E n d- of- Treat me nt ( E O T) Visit 
a n d a F oll o w- u p Visit 4 wee ks after t he last d ose of I M P. I n a d diti o n, e ver y eff ort will be ma d e t o 
ha ve all patie nts r et ur n t o t he s ite at t he ti me c orres p o n di n g t o t heir sc he d ul e d visits, partic ularl y 
t he Wee k 2 6 Visit. If t h e patie nt d oes n ot a gree t o site visits, t he y will be c o ntacte d b y tele p h o n e 
t o i n q uire a b o ut safet y st at us. 
6. 1. 3  D o u bl e- bli n d E xt e n si o n P eri o d ( W e e k 2 7 t o W e e k 7 9) 
Fr o m Wee k 2 7 t o 7 9, patie nts will be i n a 5 3- wee k d o u ble- bli n d E xte ns i o n Peri o d. Patie nts will 
c o nti n ue t o recei ve t he bli n de d me dicati o n (s ota glifl ozi n or place b o) t o w hi c h t he y were 
ra n d o mize d o n Da y 1. All patie nts will ha ve P P G assesse d f oll o wi n g a M M T T at Wee k 7 9. 
Patie nts w h o recei v e d res c ue me di cati o n d uri n g t h e 2 6- wee k C ore Treat me nt Peri o d will c o nti n ue 
o n t he sa me res c ue me di cati o n d ur i n g t h e d o u ble- bli n d E xte nsi o n Peri o d ( u nless t he I n vesti gat or 
c o nsi ders a c h a n ge n ecessar y f or s afet y reas o ns). 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 3 7 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 3 8 
6. 2. 2  D et er mi n ati o n of e n d of cli ni c al tri al ( all p ati e nt s) 
T he e n d of t he st u d y is d efi ne d as b ei n g t h e “las t patie nt last visit” pla n ne d wit h t he pr ot oc ol, 
i ncl u di n g f oll o w- u p visit. 
T he S p o ns or ca n ter mi nate t he trial pre mat urel y b ase d o n t he a d vice of t he i n de pe n de nt Dat a 
M o nit ori n g C o m mittee ( D M C) or ot her u nf oresee n de vel o p me nts. 
6. 3  
I N T E RI M A N A L Y SI S 
N o i nteri m a nal ysis is pla n ne d. 
6. 4  
S T U D Y C O M MI T T E E S 
6. 4. 1  D at a m o nit ori n g c o m mitt e e 
A D M C wit h me m bers w h o are i n de p e n de nt fr o m t h e S p o ns or a n d t he I n vesti gat ors will meet o n 
a re g ular basis, a n d will be res p o nsi ble f or: 
•  Re vie w of acc u m ulati n g cli nical trial safet y d ata b y treat me nt 
•  Ma ki n g a rec o m me n dati o n t o t he S p o ns or re gar di n g t he st u d y f oll o wi n g eac h meeti n g. 
Safet y d ata t o be re vie w e d will be u n bli n de d a n d i ncl u de e ve n ts a n d o ut c o mes descri be d b el o w 
f or a dj u dicati o n, as w ell as a n y a d diti o nal safet y d ata c o nsi dere d rel e va nt. Details descri bi n g t he 
D M C pr ocesses a n d pr oce d ures are o utli ne d i n a s e parat e D M C C harter. T o mai ntai n c o nti n u o us 
bli n di n g a n d st u d y i nte grit y, t he a n al ysis will be c o n d ucte d b y a n i n de p e n d e nt statisticia n, a n d 
meas ures will be ta k e n t o e ns ure t he v ali dit y of t he data. 
6. 4. 2  Cli ni c al e n d p oi nt c o m mitt e e( s) 
T he Cli nical E n d p oi nt C o m mittees ( C E C) is/are c o m prise d of e x perts i n car di ol o g y a n d 
ne p hr ol o g y (a n d ot her a p pr o priate  me dical s pecialties s uc h as ne ur ol o g y a n d e n d ocri n ol o g y, as 
nee de d) w h o ar e i n de pe n de nt of t he S p o ns or a n d t he c o ntract researc h or ga nizati o n ( C R O). T he 
C E Cs will re vie w a n d a dj u dicate all deat hs, maj or a d verse car di o v asc ular e ve nts 
( M A C E)/selecte d C V e v e nts ( MI, str o ke, u nsta ble a n gi n a lea di n g t o h os pitalizati o n, a n d heart 
fail ure lea di n g t o h os pitalizati o n), selecte d re nal e ve nts, b o ne fract ure, a n d D K A. 
T he details re gar di n g t he C E C pr ocesses a n d pr o ce d ures will be o utli ne d i n t he C E C C harter(s). 
6. 4. 3  S af et y a dj u di c ati o n of e v e nt s r e q uiri n g o n g oi n g m o nit ori n g 
T w o i n de pe n de nt c o m mittees will re vie w safet y e ve nts t hat re q uire o n g oi n g m o nit ori n g t o e ns ure 
ti mi n g pr ot oc ol a me n d m e nts i n case a s afet y si g n al is i de ntifie d. T hese e v e nts are: 1) p ote ntial 
cases of DI LI, a n d 2) cas es of a m p utati o ns. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 3 9 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 3 9 
T he t w o c o m mittees will re vie w t he cases i n a treat me nt- bli n de d ma n ner a n d will prese nt t heir 
assess me nt t o t he D M C. 
T he me m bers, r ol es a n d r es p o nsi bilities of t he t w o c o m mittees will be descri be d i n se parat e 
C harters. 
6. 4. 4  St e eri n g C o m mitt e e 
T he Steeri n g C o m mittee ( S C) is c o m p ose d of e x perts i n dia betes a n d s cie ntists wit h cli nical a n d 
met h o d ol o gical e x pertise. 
T his C o m mittee, le d b y a C hair, i n c olla b orati o n wit h t he S p o ns or, is res p o nsi ble f or pr o d uci n g 
a n d c o n d ucti n g a sci e ntificall y s o u n d st u d y a n d f or e ns uri n g acc urate re p orti n g of t he st u d y. I n 
t hat ca pacit y, t he S C m ust a d dress a n d res ol ve scie ntific iss ues e nc o u ntere d d uri n g t he st u d y. T he 
me m bers will re mai n bli n de d u ntil c o m pleti o n of t he st u d y. 
A m o n g its res p o nsi bilities, t he S C will recei ve bli n de d st u d y stat us re p orts fr o m S p o ns or, a n d will 
re vie w t he rec o m me n d ati o ns fr o m t he D M C t hr o u g h o ut t he st u d y. T he S C me m bers will 
partici pate i n face-t o-face meeti n gs at re g ul a r i nter vals t hr o u g h o ut t he st u d y a n d i n re g ularl y 
sc he d ule d telec o nfere nces. 
Detaile d acti vities a n d res p o nsi bilities of t he S C are pr o vi de d i n t he S C c harter. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 4 0 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 4 0 
7  
S E L E C TI O N O F P A TI E N T S 
N ote: A p atie nt s h o ul d n ot be ra n d o mize d m ore t ha n o n ce. I n cas es w here ori gi nal scree n fail ure 
was d ue t o reas o ns e x pecte d t o c ha n ge at resc ree ni n g a n d b ase d u p o n t he I n vesti gat or’s cli nical 
j u d g me nt, t he patie nt ca n be rescree n e d o nce pri or t o e nteri n g R u n-i n f or t his st u d y.  
7. 1  
I N C L U SI O N C RI T E RI A 
Patie nts meeti n g all of t h e f oll o wi n g i ncl usi o n criteria will be scree n e d: 
I 0 1. Patie nts wit h T 2 D c urre ntl y treat e d wit h diet  a n d e x ercise a n d o n metf or mi n at a sta ble 
d ose ≥1 5 0 0 m g/ da y f or at least 1 2 wee ks  
( Patie nts o n metf or mi n t hera p y at a d ose < 1 5 0 0 m g/ da y at t he ti me of e nr oll me nt ( mai ntai ne d f or 
at least 1 2 wee ks at a sta ble d ose bef ore e nr oll me nt) ma y b e eli gi ble f or s cree ni n g if 
d oc u me ntati o n of lac k of t olera nce of a metf or mi n d ose ≥1 5 0 0 m g/ da y ca n be pr o vi de d). 
I 0 2. Si g ne d writte n i nf or m e d c o nse nt 
7. 2  
E X C L U SI O N C RI T E RI A 
Patie nts w h o ha ve met all t he a b o ve i ncl us i o n crit eria liste d i n Secti o n  7. 1  will be scree n e d f or t h e 
f oll o wi n g e x cl usi o n criteria w hic h are s orte d a n d n u m bere d i n t he f oll o wi n g 4 s u bsecti o ns: 
7. 2. 1  E x cl u si o n crit eri a r el at e d t o st u d y m et h o d ol o g y 
E 0 1.  A ge < 1 8 years at t he ti m e of Scree ni n g or <le gal a ge of maj orit y, w hic h e v er is great er  
E 0 2.  T y pe 1 di a betes 
E 0 3.  B o d y mass i n de x ( B MI) ≤2 0 or > 4 5 k g/ m² at Scree ni n g 
E 0 4.  Pre vi o us use of a n y a nti dia betic dr u g ot her t h a n metf or mi n u nless t he a nti dia betic dr u g has 
bee n disc o nti n ue d f or a p eri o d of at le ast 1 2 wee ks bef ore t h e Scree ni n g Visit 
E 0 5.  Use of s yste mic gl uc oc ortic oi ds (e x cl u di n g t o pical or o p ht hal mic a p plicati o n, nasal s pra y 
or i n hale d f or ms) f or m or e t ha n 1 0 c o nsec uti v e da ys wit hi n 9 0 da ys pri or t o t he Scree ni n g 
Visit 
E 0 6.  Use of wei g ht l oss me dicati o ns wit hi n 1 2 wee ks or wei g ht c ha n ge of 5 k g or m ore d uri n g 
t he 1 2 wee ks b ef or e scr e e ni n g 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 4 1 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 4 1 
E 0 7.  Li keli h o o d of r e q uiri n g treat me nt d uri n g t he st u d y peri o d wit h dr u gs n ot per mitte d b y t he 
st u d y pr ot oc ol ( e g, l o n g-t er m s yste mic gl u c ocortic oi ds) a n d ref usi n g or u n a ble t o ta ke 
alter nati ve treat me nt 
E 0 8.  Patie nts w h o ha ve pre vi o usl y partici p ate d i n a n y cli nical  trial of s ota glifl ozi n/ L X 4 2 1 1 
E 0 9.  Patie nts wit h se vere a n e mia, se vere C V (i ncl u di n g c o n gesti ve heart fail ure Ne w Y or k 
Heart Ass o ciati o n I V), r es pirat or y, he patic, n e ur ol o gical, ps yc hiatric, or acti ve mali g na nt 
t u m or or ot her maj or s yst e mic disease or p atie nts wit h s h ort life e x pecta nc y ma ki n g 
i m ple me ntati o n of t he pr ot ocol or i nter pretati o n of t he st u d y res ults diffic ult 
E 1 0.  C urre nt dia g n osis of c hr o nic he patitis, He patitis B s urface a nti ge n p ositi ve, He patitis C 
a nti b o d y p ositi ve, a n d/ or ot her cli nicall y acti ve li v er disease re q uiri n g treat me nt 
E 1 1.  K n o w n prese n ce of fact ors t hat i nterfere wit h t he Ce ntral La b H b A 1 c meas ure me nt (e g, 
ge n etic H b varia nts) c o m pr o misi n g t he relia bilit y of H b A 1c assess me nt, or me dical 
c o n diti o ns t hat affect i nter pretati o n of H b A 1c res ults (e g, bl o o d tra nsf usi o n or se vere bl o o d 
l oss i n t he last 3 m o nt hs pri or t o ra n d o mizati o n, a n y c o n diti o n t hat s h orte ns er yt hr oc yte 
s ur vi val) 
E 1 2.  Hist or y of dr u g or al c o h ol a b use wit hi n 6 m o nt hs pri or t o scree ni n g 
E 1 3.  Patie nt is a n e m pl o yee of t he S p o ns or, or is  t he I n vesti gat or or a n y S u b-i n v esti gat or, 
researc h assista nt, p har macist, st u d y c o or di nat or, ot her staff or relati ve t h ere of directl y 
i n v ol ve d i n c o n d ucti n g t he st u d y 
E 1 4.  Patie nt w h o has ta ke n ot her i n vesti gati o nal dr u gs or pr o hi bite d t hera p y f or t his st u d y 
wit hi n 1 2 wee ks or 5 half-li ves, w hic he ver is l o n ger, pri or t o t he scree ni n g 
E 1 5.  Patie nts u n willi n g or u na ble t o perf or m se lf- m o nit ori n g of bl o o d gl uc os e ( S M B G), 
c o m plete t he patie nt diar y, or c o m pl y wit h st u d y visits a n d ot her st u d y pr o ce d ures as 
re q uire d p er pr ot oc ol 
E 1 6.  C o ntrai n dicati o n t o metf or mi n as per l ocal la b eli n g 
7. 2. 2  E x cl u si o n crit eri a r el at e d t o di a b et e s hi st or y a n d tr e at m e nt  
E 1 7.  He m o gl o bi n A 1 c < 7 % or > 1 0 % meas ure d b y  t he ce ntral la b orat or y at Scree ni n g 
E 1 8.  Fasti n g plas ma gl uc ose > 1 5 m m ol/ L ( > 2 7 0 m g/ d L)  meas ure d b y t h e ce ntral la b orat or y at 
Scree ni n g ( Visit 1), a n d c o nf ir me d b y a re peat test ( > 1 5 m m ol/ L [ > 2 7 0 m g/ d L]) bef ore 
ra n d o mizati o n 
E 1 9.  Pre vi o us use of a n y t y pes of i ns uli n f or > 1 m o nt h (at a n y ti me, e x ce pt f or treat me nt of 
gestati o nal dia b etes) 
E 2 0.  Hist or y of di a betic ket oaci d os is or n o n ket otic h y p er os m olar c oma wit hi n 1 2 wee ks pri or t o 
t he Scree ni n g Visit 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 4 2 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 4 2 
7. 2. 3  E x cl u si o n crit eri a r el at e d t o t h e c urr e nt k n o wl e d g e of s ot a glifl o zi n 
E 2 1.  Pre g n a nt (c o nfir me d b y s er u m pre g n a nc y te st at S cree ni n g) or breast-fee di n g w o me n 
E 2 2.  W o me n of c hil d beari n g p ote ntial n ot willi n g t o use hi g hl y effecti ve met h o d(s) of birt h 
c o ntr ol or w h o are u n willi n g or u n a ble t o be teste d f or pre g n a nc y (s ee A p p e n di x A ), d uri n g 
t he st u d y. 
E 2 3.  Mea n of 3 se p arat e bl o o d press ure me as ure m e nts > 1 8 0 m m H g ( S B P) or > 1 0 0 m m H g 
( D B P) 
E 2 4.  Hist or y of h y p erte nsi ve e mer ge nc y w it hi n 1 2 wee ks pri or t o Scree ni n g (1 ) 
E 2 5.  Hist or y of gastric s ur ger y, i n cl u di n g gastric b a n di n g, wit hi n 3 years or i nfl a m mat or y b o wel 
disease 
E 2 6.  Diffic ult y s wall o wi n g s u c h t hat t he patie nt ca n n ot ta ke t he I M P 
E 2 7.  K n o w n aller gies, h y p erse nsiti vit y, or i nt o lera nce t o S G L T 2 i n hi bit or or a n y i nacti ve 
c o m p o ne nt of s ota glifl ozi n or place b o (i e,  micr ocr ystalli ne cell ul ose, cr oscar mell ose 
s o di u m [ disi nte gra nt], talc, silic o ne di o xi de, a n d ma g n esi um stearate [ n o n b o vi ne]), u nless 
t he reacti o n is dee me d irrele va nt t o t he st u d y b y t h e I n vesti gat or 
E 2 8.  La b orat or y fi n di n gs wit h t he ce ntral la b orat or y tests at Visit 1 
- 
Ala ni ne a mi n otra nsf eras e ( A L T) or as partate a mi n otra nsferase ( A S T)  > 3 × t he u p per 
li mit of t he n or mal la b orat or y ra n ge ( U L N) 
- 
T otal bilir u bi n > 1. 5 × U L N (e x ce pt i n case of Gil bert’s s y n dr o me) 
- 
Ne utr o p hils < 1, 5 0 0/ m m 3 ( or acc or di n g t o et h nic gr o u p; see A p pe n di x F  f or details) 
a n d/ or platelets < 1 0 0, 0 0 0/ m m 3 
- 
A m ylase a n d/ or li pase > 3 × U L N 
E 2 9.  Se vere r e nal diseas e as d efi ne d b y e G F R  of < 3 0 m L/ mi n/ 1. 7 3 m² at scree ni n g b y t he 
4 varia ble M o dificati o n of Diet i n  Re nal Diseas e ( M D R D) e q uati o n  
E 3 0.  A n y c o u ntr y-r elate d s pe cific re g ulati o n t hat w o ul d pre ve nt t he patie nt fr o m e nteri n g t he 
st u d y 
7. 2. 4  A d diti o n al e x cl u si o n crit eri a d uri n g or at t h e e n d of t h e R u n-i n p h a s e b ef or e 
R a n d o mi z ati o n 
E 3 1.  I nf or me d c o ns e nt wit h dra wal bef ore ra n d o mizati o n ( patie nt w h o is n ot willi n g t o c o nti n ue) 
or patie nt fails t o ret ur n. 
E 3 2.  A n y cli nicall y si g nifica nt a b n or malit y i de ntifie d o n p h ysical e x a mi nati o n, la b orat or y tests, 
E C G or vital si g ns at t he ti me of scree ni n g or a n y A E d uri n g Scree ni n g p eri o d w hic h, i n 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 4 3 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 4 3 
t he j u d g me nt of t he I n vesti gat or or a n y S u b-i n vesti gat or, w o ul d precl u de safe c o m pleti o n 
of t he st u d y or c o nstrai ns efficac y ass ess me nt. 
E 3 3.  Patie nt i ns ufficie ntl y c o m plia nt d uri n g R u n-i n  p hase base d o n t a blet c o u nt ( < 8 0 %) or i n 
t he o pi ni o n of t he I n vesti gat or. 
 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 4 4 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 4 4 
8  
S T U D Y T R E A T M E N T S 
8. 1  
I N V E S TI G A TI O N A L M E DI CI N A L P R O D U C T S 
T he I M Ps are s ota glifl ozi n 2 0 0 m g a n d mat c hi n g place b o. Patie nts will be pr o vi de d wit h 7 0 ta blet 
b ottle(s) of s ota glifl ozi n 2 0 0 m g or matc hi n g place b o. Ta ble 1  pr o vi d es a s u m mar y of eac h I M P. 
T a bl e 1 - S u m m ar y of i n v e sti g ati o n al m e di ci n al pr o d u ct s 
I M P: 
S ot a glifl ozi n 
Pl a c e b o 
N a m e of t h e I M P s 
S ot a glifl ozi n ( S A R 4 3 9 9 5 4)  
Pl ac e b o 
P h ar m a c e uti c al f or m 
S ot a glifl ozi n ( S A R 4 3 9 9 5 4) will b e s u p pli e d as 
2 0 0 m g t a bl ets 
Pl ac e b o will b e s u p pli e d as t a bl ets (i d e ntic al t o 
s ot a glifl ozi n i n a p p e ar a nc e) 
D o s e, ti mi n g a n d r o ut e of 
a d mi ni strati o n 
T w o 2 0 0 m g t a bl ets, t ak e n or ally o nc e d aily, 
b ef or e first m e al of t h e d ay a 
T w o 2 0 0 m g t a bl ets, t ak e n or ally o nc e d aily, 
b ef or e first m e al of t h e d ay a 
D ur ati o n of tr e at m e nt 
7 9 w e eks f oll o wi n g r a n d o miz ati o n i ncl u di n g a 
2 6- w e ek d o u bl e- bli n d C or e Tr e at m e nt P eri o d 
a n d a 5 3- w e ek d o u bl e- bli n d Ext e nsi o n 
7 9 w e eks f oll o wi n g r a n d o miz ati o n i ncl u di n g a 
2 6- w e ek d o u bl e- bli n d C or e Tr e at m e nt P eri o d 
a n d a 5 3- w e ek d o u bl e- bli n d Ext e nsi o n 
St ora g e c o n diti o n s  
St or e b et w e e n + 1 5° C a n d + 3 0° C  
( 5 9° F a n d 8 6° F) 
 St or e b et w e e n + 1 5° C a n d + 3 0° C  
( 5 9° F a n d 8 6° F) 
I M P: I nv esti g ati o n al m e dici n al pr o d uct 
a  O n st u dy visit d ays occ urri n g o n D ay 1 ( Visit 3), W e ek 2 6 ( Visit 9), a n d W e ek 7 9 ( Visit 1 3), I M P a n d m etf or mi n s h o ul d b e a d mi ni st er e d 
acc or di n g t o t h e sc h e d ul e o utli n e d i n A p p e n dix C . 
8. 2  
N O NI N V E S TI G A TI O N A L M E DI CI N A L P R O D U C T 
8. 2. 1  M etf or mi n 
Patie nts are e nr olle d wit h a bac k gr o u n d t hera p y c o nsisti n g of metf or mi n. Bac k gr o u n d metf or mi n 
is c o nsi dere d as a n o ni n vesti gati o nal me dici n al pr o d uct ( NI M P). Metf or mi n (c o m merci al 
f or m ulati o ns) will be a d mi nistere d orall y acc or di n g t o t he l ocall y a p pr o ve d la bel. O n st u d y visit 
da ys, metf or mi n s h o ul d be ta ke n wit h t he first m eal after t he st u d y visit has c o ncl u de d, e x ce pt at 
Visits 3, 9, a n d 1 3 ( Da y 1, W ee ks 2 6 a n d 7 9), w h ere metf or mi n treat me nt s h o ul d be ta ke n 
acc or di n g t o t he i nstr ucti o ns i n A p pe n di x C . 
T he d ose of metf or mi n m ust be ≥1 5 0 0 m g/ da y a n d m ust be sta ble f or at least 1 2 wee ks bef ore 
e nr oll me nt, e x ce pt w her e d oc u me ntati o n of lac k of t olera nce of a m etf or mi n d ose ≥1 5 0 0 m g/ da y 
ca n be pr o vi d e d (see Secti o n  7. 1 ).  
T he d ose of metf or mi n s h o ul d be sta ble t hr o u g h o ut t he st u d y u nless d o w n-titrati o n is re q uire d f or 
safet y reas o ns. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 4 5 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 4 5 
Metf or mi n treat me nt is t o be re p ort e d i n t he elec tr o nic cas e re p ort f or m (e- C R F). T his i nf or mati o n 
s h o ul d i ncl u de s pecific dr u g n a me, d ose, r o ute of a d mi nistrati o n, a n d fre q u e nc y. 
T he c ost of t he bac k gr o u n d treat me nt metf or mi n  or resc u e t hera p y n ot c o v ere d b y healt h 
i ns ura nce will be rei m b urse d w here per mitte d b y l ocal re g ulati o ns. 
8. 2. 2  R e s c u e t h er a p y 
T he t hres h ol d val ues are defi ne d as  f oll o ws, d e pe n di n g o n st u d y peri o d: 
•  F P G > 2 7 0 m g/ d L ( 1 5. 0 m m ol/ L) fr o m Ra n d o mizati o n u p t hr o u g h t he s c he d ule d Wee k 8 
Visit 
•  F P G > 2 4 0 m g/ d L ( 1 3. 3 m m ol/ L) after t he Wee k 8 visit u p t hr o u g h t he sc h e d ule d Wee k 1 2 
Visit 
•  F P G > 2 0 0 m g/ d L ( 1 1. 1 m m ol/ L) after t he Wee k 1 2 Visit t hr o u g h t he e n d of t he 2 6- wee k 
C ore Treat me nt Peri o d 
•  F P G > 1 7 0 m g/ d L ( 9. 4 m m ol/ L) or H b A 1c ≥8. 0 % after t he Wee k 2 6 Visit t hr o u g h t h e e n d 
of t he treat me nt p eri o d 
R o uti ne fasti n g S M B G (s ee Secti o n  9. 2. 1. 6 ) a n d ce ntral la b orat or y alerts o n F P G (a n d H b A 1c at 
Wee k 2 6 a n d o n war d) ar e set u p t o e ns ure t h at gl yce mic para mete r res ults re mai n u n der 
pre defi n e d t hres h ol ds.  
•  If o ne f asti n g S M B G val ue e x cee ds t he s pecific gl yce mic li mit o n o ne da y, t he patie nt 
c hec ks it a gai n d uri n g t h e t w o f oll o wi n g d a ys. If all t he val ues i n t hree c o nsec uti ve da ys 
e x cee d t he s pecific li mit, t he patie nt s h o ul d c o ntact t he I n v esti gat or a n d a ce ntral 
la b orat or y F P G meas ur e me nt (a n d H b A 1 c at Wee k 2 6 a n d o n war d) be perf or me d as s o o n 
as p ossi ble, prefera bl y wit hi n 7 da ys, t o c o nfir m t h e h y p er gl yce mia.  
•  U p o n recei pt of a ce ntral la b orat or y resc ue al ert, a ce ntral la b orat or y re-test m ust be 
c o m plete d a n d c o nfir me d as e x cee di n g t he t hres h ol d f or resc u e bef ore resc u e t hera p y is 
i nitiate d. T he re-test c o nfir matio n s h o ul d be perf or me d as s o o n as p ossi ble, b ut wit hi n 
7 da ys of recei pt, b y u nsc he d ule d visit.  
I n t he e ve nt t hat a c o nfir mat or y F P G a n d/ or H bA 1c e x cee ds t he t hres h ol d, t he I n v esti gat or s h o ul d 
e ns ure t hat n o r eas o na bl e e x pla nati o n e xists f or i n s ufficie nt gl uc ose c o ntr ol a n d i n partic ular t h at: 
•  T he i ncrease d F P G has b ee n teste d at a fasti n g stat us (ie, n o f o o d i nta ke f or ≥8 h o urs) 
•  I n v esti gati o nal me dicinal pr o d uct is gi ve n at t he pl a n ne d d ose 
•  T here is n o i nterc urre nt disease, w hic h ma y j e o par dize gl yce mic c o ntr ol (e g, i nfecti o us 
disease) 
•  C o m plia nce t o treat me nt is a p pr o priate 
•  C o m plia nce t o diet a n d lif est yl e is a p pr o priat e 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 4 6 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 4 6 
If a n y of t he a b o ve ca n r eas o na bl y e x plai n t he i ns ufficie nt gl yce mic c o ntr ol, t he I n v esti gat or 
s h o ul d c o nsi der n ot i nitiati n g res c ue me dicati o n a n d s h o ul d u n derta ke a p pr o priate acti o n, ie: 
•  Assess plas ma gl uc ose i n fasti n g c o n d iti o n (ie, aft er at least 8 h o urs fast) 
•  I nitiate a n e val u ati o n a n d treat me nt of i nterc urre nt disease (t o be re p orte d i n 
A E/c o nc o mita nt me dicati o n parts of t he e- C R F a n d t he me dical rec or d) 
•  Stress t he a bs ol ute nee d t o be c o m plia nt wit h treat me nt 
•  Or ga nize a s pecific i nter vie w wit h t he patie nt a n d a Re gistere d Dietici a n or ot her q ualifie d 
n utriti o n pr ofessi o nal t o rei nf orce t he a bs ol ute nee d t o be c o m plia nt wit h diet a n d lifest yl e 
rec o m me n dati o ns, a n d s c he d ule a F P G/ H b A 1c ass ess me nt at t he ne xt visit. 
If n o ne of t he a b o ve me nti o ne d reas o ns ca n be f o u n d, or if a p pr o pri ate acti o n fails t o decrease 
F P G/ H b A 1c u n der t he t hres h ol d val ues, resc ue m e dicati o n ma y be i ntr o d u ce d. 
I nitiati o n of o pe n-la bel resc ue me dicati o n(s) t o treat h y per gl yce mia will be at t he discreti o n of t he 
I n v esti gat or a n d i n acc or da nce wit h l ocal sta n dar d of care a n d prescri bi n g practice. E x ce pt f or 
S G L T 2 i n hi bit ors, a n y a p pr o ve d me dicati o n(s) i ncl u di n g oral a nti dia b etic dr u gs or i ns uli n ca n be 
prescri be d t o treat t he h y per gl yce mia. T h e patie nt c o nti n ues t he st u d y treat me nt ( bli n de d) a n d 
sta ys i n t he st u d y i n or der t o c ollect efficac y a n d s afet y i nf or mati o n. T h e pla n ne d visits a n d 
assess me nts s h o ul d occ ur u ntil t he last sc he d ule d  visit. F or patie nts wit h re n al i m pair me nt, 
c o ntrai n dicati o ns t o a nti h y p er gl yce mic dr u gs s h o ul d be ta ke n i nt o c o ns i derati o n. If a patie nt 
re q uires gl yc e mic res c ue, t he I M P r ecei v e d d uri n g t he ra n d o mize d, d o u ble- bli n d Treat me nt 
Peri o d s h o ul d c o nti n ue a n d m ust re mai n  bli n de d u ntil t he e n d of t he st u d y. 
Resc ue t her a p y is c o nsi dere d a NI M P. Resc ue t h era p y is t o be  re p orte d i n t he e- C R F. T his 
i nf or mati o n s h o ul d i ncl u de s pecific dr u g na me, d ose, r o ute of a d mi nistrati o n, a n d fre q u e nc y. 
If n ot c o vere d b y healt h i ns ura nce, t h e c ost of t he resc ue t h era p y will be rei m b urse d w here 
per mitte d b y l ocal re g ulati o ns. 
8. 3  
B LI N DI N G P R O C E D U R E S 
8. 3. 1  M et h o d s of bli n di n g 
T o mai ntai n bli n di n g, s ota glifl ozi n a n d place b o ta blets a n d pac ka gi n g will be bli n de d a n d 
i n disti n g uis ha ble. 
D uri n g t h e d o u ble- bli n d treat me nt peri o d eac h trea t me nt pac ka ge will be labele d wit h a n u m ber, 
w hic h is ge nerate d b y a c o m p uter pr o gra m fr o m Sa n ofi. I n vesti gat ors will n ot ha ve access t o t he 
ra n d o mizati o n (treat me nt) c o de e x ce pt u n der circ u msta nces descri be d i n Secti o n  8. 3. 2 . 
T he ra n d o mizati o n a n d t he treat me nt all ocati o n will be perf or me d ce ntrall y b y a n I R T. T he st u d y 
bi ostatisticia n pr o vi des t he ra n d o mizati o n sc he me t o t he I R T. T h e n, t he I R T ge n erates t he patie nt 
ra n d o mizati o n list fr o m w hic h it all ocates treat me nt ar ms t o t he patie nts. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 4 7 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 4 8 
 At Visit 3 ( Bas eli ne), ass ess me nt res ults are re vie we d a n d baseli ne assess me nts 
are c o m plet e d, t he I R T is c o ntacte d f or ra n d o mi zati o n a n d all ocati o n of treat me nt pac ka ge.  
F or eac h ra n d o mize d patie nt, t he I R T will all ocat e a treat me nt pac ka ge n u m ber c orres p o n di n g t o 
t he treat me nt gr o u p assi g ne d. After Visit 3 ( Bas eli ne) t he I R T is c o ntacte d a gai n eac h ti me ne w 
treat me nt pac k a ge(s) all o cati o n is re q uire d b y t he pr ot oc ol. Treat ment p ac k a ges are all ocate d b y 
t he I R T usi n g t heir treat me nt kit n u m ber. 
A ra n d o mize d patie nt is defi ne d as  a patie nt w h o is re gistere d an d assi g n e d wit h a treat me nt kit 
n u m ber fr o m t he I R T, as d oc u me nte d i n I R T. 
A patie nt ma y n ot be e nr olle d i n t his st u d y m ore t ha n o nce (i e, bei n g ra n d o mize d t wice). I n cas es 
w here ori gi n al scree n fail ure was d u e t o reas o ns e x pecte d t o c ha n ge at rescree ni n g a n d b ase d u p o n 
t he I n v esti gat or’s cli nical j u d g me nt, t he patie nt ca n be rescree n e d pri or t o e nteri n g R u n-i n o nce 
f or t his st u d y. I n t hes e cases, a patie nt will nee d t o si g n a ne w I C F, b e re gistere d as a re-scree ne d 
patie nt i n I R T a n d assi g n e d a ne w p atie nt n u m ber i n I R T (first Scree ni n g Visit is t o be re gistere d 
as scree n fail ur e i n I R T), a n d a gai n c o m p let e Scree ni n g Visit pr oce d ures/ assess me nts. 
8. 5  
P A C K A GI N G A N D L A B E LI N G 
Pac ka gi n g will be u n dert a ke n i n acc or da n ce wit h t he a d mi nistrati o n sc he d ule. T he c o nte nt of t h e 
la beli n g is i n acc or d a nce wit h t he l ocal re g ulat or y s pecificati o ns a n d re q uire me nts. 
T he a p pr o pri ate n u m ber of pac ka ges will be dis pe nse d t o c o ver u p t o t he n e xt dis pe nsi n g visit 
( please r ef er t o Secti o n  1. 2 ). St ora ge c o n diti o ns a n d use- b y-e n d d ate are p art of t he la b el te xt. 
Treat me nt la bels will i n dicate t he treat me nt n u m ber ( use d f or treat me nt all ocati o n a n d re p orte d i n 
t he e- C R F). 
8. 6  
S T O R A G E C O N DI TI O N S A N D S H E L F LI F E 
I n v esti gat ors or ot her a ut h orize d pers o ns (e g, p h armacists) are res p o nsi ble f or st ori n g t he I M P i n a 
sec ure a n d saf e place i n acc or da n ce wit h l ocal re g ulati o ns, la beli n g s pecificati o ns, p olicies, a n d 
pr oce d ur es. 
C o ntr ol of I M P st ora ge c o n diti o ns, es peciall y c o nt r ol of te m perat ure a n d i nstr ucti o ns f or ha n dli n g 
t he Sa n ofi c o m p o u n d s h o ul d be ma na ge d acc or di n g t o t he r ules pr o vi de d b y t he S p o ns or. 
T he e x pir y dat e a n d st ora ge c o n diti o ns are writte n o n t he I M P la b els. T he I M P s h o ul d be st ore d 
bet wee n + 1 5° C a n d + 3 0° C ( 5 9° F a n d 8 6° F). 
8. 7  
R E S P O N SI BI LI TI E S 
T he I n vesti gat or, t he h os pital p har macist, or ot he r pers o n nel all o we d t o st ore a n d dis pe ns e t he 
I M P will be r es p o nsi ble f or e ns uri n g t hat t he I M P use d i n t he cli nical trial is sec urel y mai ntai ne d 
as s pecifie d b y t he S p o ns or a n d i n acc or da n ce wit h a p plica ble re g ulat or y re q uire me nts. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 4 9 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 4 9 
All I M Ps will be dis pe ns e d i n acc or da nce wit h t he I n v esti gat or's pres cri pti o n a n d it is t he 
I n v esti gat or's res p o nsi bilit y t o e ns ure t h at a n acc urate rec or d of I M P iss ue d a n d ret ur n e d is 
mai ntai ne d. 
A n y q u alit y iss ue n otice d wit h t he recei pt or us e of a n I M P ( defici e nc y i n c o n diti o n, a p peara n ce, 
pertai ni n g d o c u me ntati o n, la beli n g, e x pirati o n date, etc) s h o ul d be pr o m ptl y n otifie d t o t he 
S p o ns or or Dele gat e. S o me deficie n cies ma y be rec or de d t hr o u g h a c o m pl ai nt pr oce d ure. 
A p ote ntial defect i n t he q ualit y of I M P ma y be s u bject t o i nitiati o n of a recall pr oce d ure b y t he 
S p o ns or. I n t his cas e, t he I n v esti gat or will be res p o nsi ble f or pr o m ptl y a d dressi n g a n y re q u est 
ma de b y t he S p o ns or or Dele ga te, i n or d er t o recall t he I M P a n d eli mi nate p ote ntial hazar ds. 
U n der n o circ u msta nces will t he I n vesti gat or s u p pl y I M P t o a t hir d part y (e x ce pt f or 
direct-t o- patie nt s hi p me nt, f or w h ic h a c o urier c o m pa n y h as bee n a p pr o ve d b y t he S p o ns or), all o w 
t he I M P t o be us e d ot her t ha n as direct e d b y t his cli nical trial pr ot oc ol, or dis p ose of I M P i n a n y 
ot her ma n ner. 
8. 7. 1  Tr e at m e nt a c c o u nt a bilit y a n d c o m pli a n c e 
Acc o u nti n g a n d c o m plia nce f or I M Ps will be perf or me d at Visit 3 a n d all s u bse q ue nt visits 
(e x cl u di n g A B P M place me nt Visits).  
T he I n vesti gat or will c h ec k t he c o m plia nce t o t he I M P d ose sc h e d ule bas e d o n t he patie nt diar y 
a n d will t he n c o m plete t he a p pr o pri ate Site treat m e nt a n d patie nt treat me nt l o g f or ms. Ret ur n e d 
I M P s h o ul d be c o u nt e d b y site staff. I n a d ditio n t he d osi n g i nf or mati o n will be rec or de d o n t he 
a p pr o priate p a ges of t h e e- C R F. 
F or NI M P metf or mi n, na me, start a n d e n d d ate of treat me nt, t otal dail y d os e, etc, will be 
d oc u me nte d i n t he s o urce d oc u me nts. C o m plia nce t o metf or mi n will be c h ec ke d b y i nter vi e wi n g 
t he patie nt a n d re vi e wi n g diar y at eac h visit an d be d oc u me nte d i n t he s o urce d oc u me nts a n d i n 
t he e- C R F. 
If c o m plia nce is i na de q u ate as deter mi ne d b y t he Pri nci pal I n v esti gat or ( PI), patie nts will be 
trai ne d a gai n a n d me nt ore d. If s u b o pti mal c o m plia nce c o nti n ues after trai ni n g a n d me nt ori n g, 
patie nts ma y b e disc o nti n ue d at t he discreti o n of  t he PI after dis c ussi o n wit h t he S p o ns or’s 
me dical m o nit or. 
8. 7. 2  R et ur n a n d/ or d e str u cti o n of tr e at m e nt s 
Patie nts are t o ret ur n all I M P ( u n use d, i n use or e m pt y b ottle[s]) at eac h o n-site visit (e x ce pt 
A B P M visits f or w hic h I M P acc o u nti n g is n ot re q uire d, as descri be d i n Secti o n 1. 2 ).  
At Visit 4 ( Wee k 1), beca use n o I M P re-s u p pl y is pl a n ne d d uri n g t his visit, patie nts will be se nt 
h o me after t his visit wit h t he i n- use b ottle(s) dis pe nse d at ra n d o mizati o n. 
Patie nts are t o ret ur n all t he use d, i n- use a n d u n use d I M P at Visit 1 3 ( or fi n al assess me nt 
o n-treat me nt visit i n case of per m a n e nt pre mat ure disc o nti n uati o n).  
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 5 0 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 5 0 
All use d, partiall y- use d or u n use d I M Ps will be retrie ve d b y t he S p o ns or or Dele gate. A detaile d 
site a n d patie nt treat me nt l o g of t he ret ur ne d I M P will be esta blis he d wit h t he I n vesti gat or ( or t he 
p har macist) a n d c o u ntersi g ne d b y t he I n vesti gat or a n d t he m o nit ori n g tea m. 
8. 8  
C O N C O MI T A N T M E DI C A TI O N 
A c o nc o mita nt me dicati o n is a n y treat me nt recei v e d b y t h e patie nt c o n c o mita ntl y t o a n y I M P(s). 
T he I M P i ncl u des place b o a n d s ota glifl ozi n 4 0 0 m g. 
All c o nc o mita nt me di cati o ns s h o ul d be d oc u me nte d o n t he Me dicati o ns pa ge of t he e- C R F. T his 
i ncl u des all NI M P treat m e nts t hat are ta k e n b y t he patie nts at a n y ti me d uri n g t he cli nical trial, 
be gi n ni n g at Visit 1.  
A d diti o nall y, all me dicati o ns ta ke n i n t he 3 m o nt hs pri or t o Visit 1 a n d pri or use of S G L T 2 
i n hi bit ors s h o ul d be re p orte d. 
8. 8. 1  Pr o hi bit e d pri or a n d c o n c o mit a nt m e di c ati o n s 
D uri n g t h e st u d y tr eat me nt peri o d, t he f oll o wi n g me dicati o ns are pr o hi bite d: 
•  I nitiati o n of a n y a nti dia betic a ge nts, i ncl u di n g oral or i njecta ble a nti h y per gl yce mic a ge nts 
ot her t ha n t he I M P is n ot all o we d bef ore t he resc u e t hera p y 
•  S yste mic use of gl uc o c ortic oi ds is n ot all o we d f or m ore t ha n 1 0 c o nsec uti ve da ys (t o pical, 
o p ht hal mic, nasal s pra y or i n hale d a p plicati o ns are all o we d) 
•  I nitiati o n of a n y wei g ht l oss dr u gs (e g, p he nter mi ne, orlistat)  
•  I n v esti gati o nal me dicinal pr o d ucts i n a n y ot her cli nical st u d y 
•  S G L T 2 i n hi bit ors (e g, ca na glifl ozi n, da pa glifl o zi n, or e m pa glifl ozi n) are n ot all o we d f or 
resc ue 
Re d ucti o n of di g o xi n d ose s h o ul d be c o nsi dere d b eca use s ot a glifl ozi n acts as a wea k P- g p 
i n hi bit or a n d i ncreases s yste mic e x p os ure t o di g o xi n. Patie nts ta ki n g s ota glifl ozi n wit h 
c o nc o mita nt di g o xi n s h o ul d ha ve di g o xi n c o nce ntrati o ns m o nit ore d a n d d oses re d uce d as nee de d. 
I n a d diti o n, ot her P- g p s u bstrates ma y be affecte d a n d t he la bels of P- g p s u bstrate dr u gs s h o ul d be 
c o ns ulte d wit h re gar ds t o m o nit ori n g a n d d ose a dj ust me nts. 
Ot her me dicati o ns w hic h are u nli kel y t o i nterfer e wit h t he P K or P D of t he I M P or c o nf o u n d 
i nter pretati o n of t he st u d y e n d p oi nts are all o w ed as nee de d f oll o wi n g disc ussi o n bet wee n t he 
I n v esti gat or a n d t he S p o ns or. H o we ver, d oses of c hr o nicall y a d mi niste re d me dici nes s h o ul d be 
ke pt fi x e d d uri n g t he trial if at all p ossi ble. 
After pr e mat ure p er ma n e nt disc o nti n uati o n of t he I M Ps, a n y treat me nts ( ot her t ha n S G L T 2 
i n hi bit ors) are per mitte d, as dee me d n ecess ar y b y t he I n vesti gat or. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 5 1 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 5 1 
T he d ose of all a nti h y perte nsi ve a ge nts s h o ul d be ke pt c o nsta nt d uri n g t he 1 2 wee ks f oll o wi n g 
ra n d o mizati o n a n d n o a nti h y pert e nsi ve a ge nts sh o ul d be a d de d or wit h dra w n f or t he 1 2 wee ks 
f oll o wi n g r a n d o mizati o n u nless it is c o nsi dere d necessar y f or safet y reas o ns. 
8. 8. 2  C o n c o mit a nt di a b et e s t h er a p y 
F or patie nts i n b ot h gr o u ps, bac k gr o u n d metf or mi n  s h o ul d be sta ble t hr o u g h o ut t he st u d y u nless 
d o w n-titrati o n is re q uire d f or safet y reas o ns. 
N o n-I M P treat me nt is defi ne d as t he resc ue m e dicati o n(s) t hat will be use d t o treat h y p er gl yce mia 
w he n a patie nt’s h y p er gl yce mia reac h es t he res c u e t hres h ol d. E x ce pt f or S G L T 2 i n hi bit ors, a n y 
a p pr o ve d me dicati o n(s) i ncl u di n g or al a nti dia betic dr u gs or i ns uli n ca n be prescri be d at t he 
I n v esti gat or’s discreti o n t o treat t he h y per gl yce mia. T he re gi me n of t h e res c ue me dicati o ns will be 
i n acc or d a nce wit h l ocal sta n dar d of care a n d pres cri bi n g practice. 
8. 9  
P O S T S T U D Y T R E A T M E N T 
Beca use s ota glifl ozi n ma y re d uce B P, a dj ust me nt of a nti h y p erte nsi ve me di cati o n ma y be nee de d 
d uri n g t he st u d y i n patie nts wit h h y perte nsi o n. C o n versel y, m o nit ori n g f or a n i ncrease i n B P 
s h o ul d be perf or m e d after wit h dra wal of st u d y me dicati o n. If t he B P is ele v ate d after wit h dra w al 
of st u d y tr eat me nt, t he I n vesti gat or s h o ul d c o nsi d er a d di n g or a dj usti n g a nti h y perte nsi ve 
me dicati o n. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 5 2 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 5 2 
9  
A S S E S S M E N T O F I N V E S TI G A TI O N A L M E DI CI N A L P R O D U C T 
9. 1  
E F FI C A C Y E N D P OI N T S 
9. 1. 1  Pri m ar y effi c a c y e n d p oi nt 
•  C ha n ge fr o m Baseli ne t o Wee k 2 6 i n H b A 1c ( %). 
9. 1. 2  S e c o n d ar y effi c a c y e n d p oi nt s 
T he c o nti n u o us sec o n dar y efficac y e n d p oi nts are: 
•  C ha n ge fr o m Baseli ne t o Wee k 2 6 i n 2- h o ur P P G f oll o wi n g a M M 
•  C ha n ge fr o m Baseli ne t o Wee k 2 6 i n F P G 
•  C ha n ge fr o m Baseli ne t o Wee k 2 6 i n b o d y w ei g ht 
•  C ha n ge fr o m Baseli ne t o Wee k 1 2 i n S B P f or patie nts wit h baseli ne S B P ≥1 3 0 m m H g 
•  C ha n ge fr o m Baseli ne t o Wee k 1 2 i n S B P f or all patie nts 
•  Pr o p orti o n of patie nts wit h H b A 1c < 6. 5 %, < 7. 0 % at Wee k 2 6. 
9. 1. 3  Ot h er effi c a c y e n d p oi nt s 
•  C ha n ge fr o m Baseli ne t o Wee k 1 2 i n S B P f or patie nts wit h baseli ne S B P < 1 3 0 m m H g 
•  Pr o p orti o n of patie nts wit h re d ucti o n i n b o d y w ei g ht b y ≥2 %, ≥5 %, a n d ≥1 0 % fr o m 
Baseli ne  
•  C ha n ges fr o m Baseli ne t o Wee k 1 2 i n D B P 
•  Pr o p orti o n of patie nts ac hie vi n g S B P < 1 3 0 m m H g f or t h ose wit h Baseli ne 
S B P ≥1 3 0 m m H g 
•  Pr o p orti o n of patie nts ac hie vi n g D B P < 8 0 m m H g f or t h ose wit h Baseli ne D B P ≥8 0 m m H g 
•  Pr o p orti o n of patie nts re q uiri n g  resc ue f or h y per gl yce mia 
•  C ha n ge fr o m Baseli ne i n: 
- 
Uri ne A C R, U G E, a n d uri ne G C R 
- 
Ser u m creati ni ne 
- 
e G F R 
•  
C ha n ge fr o m Baseli ne t o Wee k 7 9 i n H b A 1c 
•  
C ha n ge fr o m Baseli ne t o Wee k 7 9 i n F P G 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 5 3 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 5 3 
•  
C ha n ge fr o m Baseli ne t o Wee k 2 6 i n S B P f or all patie nts a n d f or patie nts wit h Baseli ne 
S B P ≥1 3 0 m m H g 
•  
C ha n ge fr o m Baseli ne t o Wee k 7 9 i n S B P f or all patie nts a n d f or patie nts wit h Baseli ne 
S B P ≥1 3 0 m m H g 
•  
C ha n ge fr o m Baseli ne t o Wee k 7 9 i n b o d y w ei g ht. 
9. 1. 4  A s s e s s m e nt m et h o d s of effi c a c y e n d p oi nt s 
9. 1. 4. 1  H e m o gl o bi n A 1 c 
He m o gl o bi n A 1 c will be assesse d at Scree ni n g ( Visit 1) a n d all o n-site visits d uri n g t he 
d o u ble- bli n d treat me nt p eri o d wit h t he e x ce pti o n of  Wee k 1 ( Visit 4) a n d t he A B P M place me nt 
Visits 3 A, 7 A, a n d 9 A. 
F or t he eli gi bilit y a n d efficac y ass ess me nts of t he st u d y, H b A 1 c is meas ure d b y a certifi e d le vel I 
“ Nati o nal Gl yc o h e m o gl o bi n Sta n dar dizati o n Pr o gra m” ce ntral la b orat or y t o all o w esti mati o n of 
t he c ha n ge fr o m Baseli ne t o Wee k 2 6 i n H b A 1c a n d t he pr o p orti o n of patie nts wit h H b A 1c 
< 6. 5 %, < 7. 0 % at Wee k 2 6. 
If a patie nt n ee ds t o recei ve resc u e a nti diabetic me dicati o n, assess me n t of H b A 1c s h o ul d be 
perf or me d b ef or e t he i ntr o d ucti o n of t he resc u e m e dicati o n. 
9. 1. 4. 2  P o st pr a n di al gl u c o s e a n d mi x e d m e al t ol er a n c e t e st 
Patie nts will u n der g o ass ess me nt of P P G at Bas eli ne ( Visit 3) a n d Wee k 2 6 ( Visit 9) via a mi x e d 
meal t olera nc e test ( M M T T) t o all o w esti mati o n of c ha n ge fr o m Baseli ne t o Wee k 2 6 i n 2- h o ur 
P P G f oll o wi n g a M M. A n M M T T will als o be perf or me d at Wee k 7 9 ( Visit 1 3). F ull details of t he 
M M T T pr oce d ur e at Bas eli ne, Wee k 2 6, a n d Wee k 7 9 are prese nte d i n A p pe n di x C . 
At Baseli ne ( Visit 3), Wee k 2 6 ( Visit 9), a n d We e k 7 9 ( Visit 1 3), P P G will  be assesse d b y M M T T 
at baseli ne (f asti n g) a n d 2 h o ur s after c o ns u mi n g a sta n dar d mi x e d li q ui d brea kfast meal. 
T he first d ose of d o u ble- bli n d I M P a n d metf or mi n o n Da y 1 ( Baseli ne; Visit 3) will be gi ve n after  
c o m pleti o n of t he 2- h o ur P P G c ollecti o n. 
F or t he Wee k 2 6 ( Visit 9) a n d Wee k 7 9 ( Visit 1 3) sta n dar dize d M M, t he patie nt s h o ul d ta ke t he 
d ose of d o u ble- bli n d I M P i m me diatel y after t he fasti n g bl o o d sa m ples are o btai ne d, a n d 
a p pr o xi matel y 3 0 mi n utes bef ore  i n gesti o n of t he sta n dar dize d M M be gi ns. At Wee k 2 6 a n d 
Wee k 7 9, metf or mi n is gi ve n after  c o m pleti o n of t he 2- h o ur P P G c ollecti o n. 
Plas ma c o nce ntr ati o n sa m ples at  Wee k 2 6 a n d Wee k 7 9 s h o ul d be ta ke n at t he sa me ti mes as t he 
fasti n g bl o o d sa m ple a n d t he 2- h o ur ce ntral la b orat or y plas ma P P G c ollecti o n (see 
Secti o n  9. 3. 1. 1 ). 
T he c o m p ositi o n a n d t he q ua ntit y of t he sta n d ar d mi x e d li q ui d brea kfast m eal m ust be i de ntical 
t hr o u g h o ut t he st u d y; see A p pe n di x C  f or f urt her details. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 5 4 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 5 4 
A n y p atie nt w h o re q uir es t he a d diti o n of resc u e me dicati o n pri or t o Wee k 2 6 or Wee k 7 9 s h o ul d 
still ha ve t he sta n dar dize d M M perf or me d as sc he d ule d. 
I n case of per m a ne nt disc o nti n uati o n of t he treat me nt wit h I M P bef ore Wee k 2 6 a n d/ or Wee k 7 9, 
e ver y eff ort will be ma d e t o ha ve t he patie nt ret ur n t o t he site at t he ti me of t heir Wee k 2 6 a n d 
Wee k 7 9 visits; h o we ver t he M M T T s h o ul d n ot be pe rf or me d at t hese or a ny ot her visit f oll o wi n g 
a Pre mat ure E O T visit. 
O n t he da ys of t he M M T T, patie nts will c o me t o t he i n vesti gati o nal site i n t he m or ni n g, i n fasti n g 
c o n diti o ns f or at least 8 h o urs a n d m ust n ot eat  a n y f o o d or dri n k, e x ce pt w ater, bef ore t he 
sc he d ule d sta n dar diz e d meal test. 
T he e x act ti mes of t he I M P a d mi nistrati o n, sta n dar d  mi x e d li q ui d brea kfast meal i nta ke, a n d t he 
bl o o d dra ws ar e t o be d o c u me nte d. 
9. 1. 4. 3  F a sti n g pl a s m a gl u c o s e m e a s ur e m e nt 
Plas ma gl uc ose is meas ure d i n t he fasti n g state at Scree ni n g ( Visit 1) a n d all o n-site visits d uri n g 
t he treat me nt peri o d wit h t he e x ce pti o n of t he A B P M place me nt Visits 3 A, 7 A, a n d 9 A. F or t he 
eli gi bilit y a n d efficac y assess me nts of t he st u d y, F P G is meas ure d at a ce ntral la b orat or y t o all o w 
esti mati o n of c ha n ge fr o m Baseli ne t o Wee k 2 6 i n F P G. 
9. 1. 4. 4  B o d y w ei g ht m e a s ur e m e nt 
B o d y wei g ht is meas ur e d at all o n-site Visits, wit h t he e x ce pti o n of t he A B P M place me nt 
Visits 3 A, 7 A, a n d 9 A. B o d y w ei g ht will be meas ure d t o all o w t he esti mati o n of c ha n ge fr o m 
Baseli ne t o Wee k 2 6 i n b o d y w ei g ht a n d re d u cti o n i n b o d y wei g ht b y ≥2 %, ≥5 %, a n d ≥1 0 % fr o m 
Baseli ne. 
B o d y wei g ht s h o ul d be o btai ne d wit h t he patie nt  weari n g u n der gar m e nts or ver y li g ht cl ot hi n g 
a n d n o s h oes, a n d wit h a n e m pt y bla d d er. 
T he sa me scale s h o ul d be use d t hr o u g h o ut t he st u d y, a n d cali brat e d o n a re g ular basis as 
rec o m me n de d b y t h e ma n ufact ur er. Cali brati o n sh o ul d be d oc u me nte d i n s o urce d oc u m e nts. T he 
use of bala n ce scales is r ec o m me n de d. T h e fl o or s u rface o n w hic h t he s cale rests m ust be har d a n d 
s h o ul d n ot be car pet e d or c o vere d wit h ot her s oft material. T he sc ale s h o ul d be bala nce d wit h b ot h 
wei g hts at zer o a n d t he b ala nce b ar ali g ne d. T h e p a tie nt s h o ul d sta n d i n t he ce nter of t he platf or m 
as sta n di n g off- ce nter m a y affe ct meas ure me nt.  T h e wei g hts are m o ve d u ntil t he bea m bala nces 
(t he arr o ws ar e ali g ne d). T he wei g ht is rea d a n d rec or de d i n t he e- C R F a n d S o urce Data. S elf-
re p orte d w ei g hts are n ot acce pta ble; patie nts m ust n ot rea d t he scales t he msel ves. 
9. 1. 4. 5  Bl o o d pr e s s ur e e n d p oi nt m e a s ur e m e nt s 
S yst olic B P a n d D B P will be assesse d at all o n-site visits, wit h t he e x ce pti o n of t he A B P M 
place me nt Visits 3 A, 7 A, a n d 9 A.  Bl o o d press ure meas ure me nts m ust  be ta ke n as descri be d i n 
Secti o n  9. 2. 1. 4  wit h details pr o vi de d i n A p pe n di x E.  
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 5 5 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 5 5 
9. 1. 4. 6  Ki d n e y f u n cti o n p ar a m et er m e a s ur e m e nt 
Ser u m creati ni ne a n d uri ne al b u mi n, creati ni ne, a n d gl uc os e are assesse d at Baseli ne ( Visit 3) a n d 
all s u bse q ue nt o n-site Visits wit h t he e x ce ptio n of A B P M place m e nts Visits 3 A, 7 A, a n d 9 A. A 
ce ntral la b orat or y will a n al yze sa m ples a n d esti mate c ha n ge fr o m Baseli ne i n uri ne A C R, U G E, 
uri ne G C R, ser u m creati ni ne, a n d e G F R ( b y t he 4 varia ble M D R D e q uati o n). T o pre ve nt p artial 
u n bli n di n g, U G E, a n d G C R res ults will be mas ke d t o i n vesti gati o nal sites a n d patie nts. 
9. 1. 4. 7  Pr o p orti o n of p ati e nt s r e q uiri n g r e s c u e f or h y p er gl y c e mi a 
T he use of r esc ue m e dicati o ns f or h y p er gl yce mia  will be assesse d a n d rep orte d t hr o u g h o ut t he 
treat me nt peri o d. R o uti ne alerts o n F P G a n d/ or H bA 1c will be se nt t o t he I n vesti gat or fr o m t he 
ce ntral la b orat or y t o e ns ure t hat gl yce mic p ara met er res ults re m ai n wit hi n pre defi n e d t hres h ol ds. 
F or details a n d f urt her acti o ns s h o ul d F P G a n d/ or  H b A 1c val ues fall a b o ve t hres h ol ds, ref er t o 
Secti o n  8. 2. 2 . 
9. 2  
S A F E T Y E N D P OI N T S 
Assess me nts f or saf et y i ncl u de A Es, S M B G, cli nical la b orat or y assess me nts, p h ysical 
e x a mi nati o n, electr ocar di o gr a m ( E C G), w ei g ht, a n d vital si g ns. A n i n de pe n de nt D M C will meet 
o n a re g ular basis t o re vi e w acc u m ulati n g cli nical trial safet y data. 
A dj u dicati o n of all deat hs, M A C E/ ot her selecte d C V  e ve nts ( MI, str o ke, u nsta ble a n gi na lea di n g 
t o h os pitalizati o n, a n d heart fail ure l ea di n g t o h os pitalizati o n), selecte d re n al e ve nts, b o ne 
fract ure, a n d D K A will b e perf or me d i n a bli n de d ma n ner b y a C E C(s) c o m prise d of e x perts. 
Details will be pr o vi de d i n t he c harter of t h e C E C(s). F urt her details are a v aila ble i n Secti o n  6. 4 . 
T w o e x pert c o m mittees will re vie w all p ote ntial cases of DI LIs a n d cases of a m p utati o n i n a 
treat me nt- bli n de d ma n ner t o e val uate ca usalit y. 
T he f oll o wi n g s afet y e n d p oi nts will be assesse d: 
•  A d verse e ve nts, A Es lea di n g t o disc o nti n uati o n fr o m t he I M P, a d v erse e ve nts of s pecial 
i nterest ( A E SIs), e ve nts of s pecial i nterest ( E O SIs), S A Es a n d deat hs 
•  H y p o gl yce mia (all, se v er e, a n d/ or d oc u me nt e d s y m pt o matic h y p o gl yce mia) 
•  Cli nical la b orat or y res ults (i ncl u di n g fasti n g li pi ds; see Secti o n  9. 2. 1. 3 ), vital si g ns, a n d 
E C G res ults 
•  Mar kers of b o ne a n d calci u m meta b olis m  
•  Mar kers of i ntesti nal tra nsit a n d a bs or pti o n 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 5 6 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 5 6 
O bser v ati o n peri o d of s afet y e n d p oi nts  
T he o bser vati o n peri o d of safet y dat a will be di vi de d i nt o 3 se g me nts: 
•  T he pre-treat me nt peri o d is defi ne d as t he ti me bet wee n t he d ate of t he i nf or me d c o nse nt 
a n d t he first d ose of d o u ble- bli n d I M P.  
•  T he o n-treat me nt peri o d ( T E A E peri o d) is defi ne d as t he ti me fr o m t he first d ose of 
d o u ble- bli n d I M P u p t o 1 0 da ys ( 1 da y f or h y p o gl yce mia) after t he l ast d ose of d o u ble-
bli n d I M P, re gar dless of t he i n tr o d ucti o n of resc u e t hera p y. T he 1 0- da y i nt er val is c h ose n 
base d o n t he half-life of t he I M P (a p pr o xi matel y 5 ti mes t he half-life of s ot a glifl ozi n) i n 
patie nts wit h m o derate r e nal d ysf u n cti o n. 
•  T he p ost-treat me nt p eri o d is defi ne d as t he ti me st arti n g 1 1 d a ys after t he last d ose of 
d o u ble- bli n d I M P ( after t he o n-treat me nt peri o d).  
T he baseli ne v al ue f or s afet y e n d p oi nts i n t he safe t y p o p ulati o n is t he last a vaila ble val ue ( or t he 
a vera ge of all val ues f or creati ni ne or e G F R) pri o r t o t he first a d mi nistrati o n of d o u ble- bli n d I M P. 
9. 2. 1  A s s e s s m e nt m et h o d s of s af et y e n d p oi nt s 
9. 2. 1. 1  A d v er s e e v e nt s 
A d verse e ve nts i ncl u di n g S A E, A E SI, a n d E O SI will be assesse d. Refer t o Secti o n  1 0. 4  t o 
Secti o n  1 0. 7  f or details. 
9. 2. 1. 1. 1  A d v er s e e v e nt s of s p e ci al i nt er e st 
A d verse e ve nts of s pecial i nterest are liste d i n Secti o n  1 0. 4. 1. 3 , re p orti n g re q uire me nts f or A E SI 
are pr ese nte d i n Secti o n  1 0. 4. 4 . 
9. 2. 1. 1. 2  E v e nt s of s p e ci al i nt er e st 
E ve nts of s pecial i nter est are se p arat e fr o m A E SIs.  F or a list of e v e nts defi ne d as E O SIs a n d t heir 
re p orti n g re q uire me nts see Secti o n  1 0. 4. 1. 4  a n d Secti o n  1 0. 4. 5, res pecti vel y. 
9. 2. 1. 2  H y p o gl y c e mi a 
H y p o gl yce mia will be assesse d fr o m Visit 2 o n war ds a n d c o nti n ue u ntil 4 wee ks after t he last 
d ose of I M P ( n ote: f or p atie nts w h o disc o nti n ue treat me nt bef ore Wee k 7 9, safet y data will be 
c ollecte d u ntil sc he d ule d st u d y e n d). Patie nts will als o c o m plete t he h y p o gl yce mia l o g (as p art of 
t he patie nt diar y) fr o m Visit 2 o n war ds, w hic h will be re g ularl y re vie w e d b y I n v esti gat ors. See 
Secti o n  1 0. 6. 1  f or f urt her details. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 5 7 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 5 7 
9. 2. 1. 3  L a b or at or y s af et y v ari a bl e s 
T he cli nical la b orat or y d ata c o nsist of bl o o d a nal ys is (i ncl u di n g he mat ol o g y, cli nical c he mistr y, 
a m ylas e, li pase, li pi d pr ofile) a n d uri nal ysis, acc or di n g t o t he sc he d ul e pres e nte d i n Secti o n  1. 2 . 
Cli nical la b orat or y val ues will be a nal yze d after c o n versi o n i nt o sta n da r d i nter nati o nal u nits. 
I nter nati o nal u nits will be use d i n all listi n gs a n d t a bles. Ta ble 2  lists t he he mat ol o g y, cli nical 
c he mistr y, a n d ot her bl o o d safe t y para meters t o be assessed b y t he ce ntral l a b orat or y. 
Alerts t o t he I n vesti gat or are set u p f or s peci fic la b orat or y a b n or m alities. I n vesti gat ors s h o ul d 
re vie w t hes e alerts a n d f oll o w- u p if nee de d as per his/ her me dical j u d ge me nt. Re-tests at ce ntral 
la b orat or y are acce pta ble if nee de d. 
I n a d diti o n, f or W O C B P a ser u m pre g n a nc y test is perf or me d at Scree ni n g, a n d uri ne pre g na nc y 
tests are ta ke n at all o n-site visits d uri n g t he d o u ble- bli n d treat me nt peri o d e x cl u di n g Visit 4 
( W ee k 1) a n d A B P M place me nt Visits 3 A, 7 A, a n d 9 A. A n y p ositi ve uri n e test res ults m ust be 
c o nfir me d b y a s er u m pr e g n a nc y test. T h e I n vest i gat or m a y perf or m a d diti o nal tests at t heir 
discreti o n or as r e q uire d b y l ocal re g ulati o ns. 
Ser u m f ollicle sti m ulati n g h or m o n e ( F S H) a n d estra di ol will be  meas ure d i n me n o pa usal w o me n 
at scree ni n g ( Visit 1, Wee k - 4) (s ee A p p e n di x A  f or defi niti o n of me n o pa usal w o me n). 
T a bl e 2 - S er u m c h e mi str y p ar a m et er s 
Cli ni c al c h e mi str y 
H e m at ol o g y 
Ot h er bl o o d p ar a m et er s 
S o di u m 
C o m pl et e bl o o d c o u nt ( C B C) 
Li pi d pr ofil e 
P ot assi u m 
Diff er e nti al 
T ot al c h ol est er ol ( T C) 
C hl ori d e 
Pl at el et c o u nt 
Hi g h- d e nsity li p o pr ot ei n c h ol est er ol ( H D L- C) 
C ar b o n di oxi d e ( bic ar b o n at e) 
H e m o gl o bi n 
L o w- d e nsity li p o pr ot ei n c h ol est er ol ( L D L- C) will b e 
c alc ul at e d by Fri e d w al d e q u ati o n 
Bl o o d ur e a nitr o g e n ( B U N) 
H e m at ocrit 
N o n- H D L C will b e c alc ul at e d as t h e diff er e nc e 
b et w e e n T C a n d H D L C 
Cr e ati ni n e ( e G F R will b e 
c alc ul at e d) 
 Tri glyc eri d es
 ( T G)
Gl uc os e (s er u m) 
 
Bl o o d M ark ers of I nt e sti n al Tra n sit a n d 
A b s or pti o n a 
Al a ni n e a mi n otr a nsf er as e ( A L T) 
 
Vit a mi ns: B 6, B 1 2, K, E, A 
As p art at e a mi n otr a nsf er as e ( A S T) 
 
Ser u m f ol at e 
T ot al bilir u bi n ( T B) 
 
F erriti n 
Alk ali n e p h os p h at as e ( A L P) 
 
M ark ers of b o n e a n d c al ci u m met a b oli s m b 
Uric aci d  
  
C alci u m 
C alci u m
 
  
2 5- hy dr oxyvit a mi n
 
D
P h os p h or us
 
  
1, 2 5- di hy dr oxyvit a mi n
 
D
 
T ot al pr ot ei n 
 
Ph os p h or us 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 5 8 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 5 8 
Cli ni c al c h e mi str y 
H e m at ol o g y 
Ot h er bl o o d p ar a m et er s 
Al b u mi n 
 
Par at hyr oi d h or m o n e ( P T H) 
M a g n esi u m 
 
M ark ers of b o n e r es or p ti o n: N-t er mi n al t el o p e pti d e 
( N T X), b et a- C-t er mi n al t el o p e pti d e (β - C T X- 1) 
Cr e ati n e p h os p h oki n as e ( C P K) 
 
M ark er of b o n e f or m ati o n: ty p e 1 pr oc oll a g e n 
N-t er mi n al ( P 1 N P) 
L actic aci d d e hy dr o g e n as e ( L D H)  
 
 
A myl as e
 
 
 
Li p as e
 
 
 
All ass ess m e nts t o b e p erf or m e d by c e ntr al l a b or at ory. All ass ess m e nt m e as ur e d i n s er u m. 
a  T o b e c oll ect e d at B as eli n e ( Visit 3), W e ek 2 6 ( Visit 9), W e ek 7 9 ( Visit 1 3), a n d F oll o w- u p Visit ( Visit 1 4). 
b  T o b e c oll ect e d at B as eli n e ( Visit 3), W e ek 2 6 ( Visit 9), a n d W e ek 7 9 ( Visit 1 3). Uri n e m ark ers of b o n e a n d c alci u m m et a b olis m ar e list e d 
i n S ecti o n  9. 2. 1. 3 . 
9. 2. 1. 3. 1  Uri n al y si s 
Uri nal ysis ( uri ne di pstic k wit h micr osc o p y) will be perf or me d b y ce ntral la b orat or y at Scree ni n g 
( Visit 1), Bas eli ne ( Visit 3), Wee k 2 6 ( Visit 9), a n d Wee k 7 9 ( Visit 1 3). T o pre ve nt partial 
u n bli n di n g, U G E res ults will be bli n de d t o i n vesti gati o nal sites a n d p atie nts, a n d t he ce ntral 
la b orat or y U A di pstic k will n ot i ncl u de t he meas ure me nt of uri ne gl uc os e. Ce ntral uri nal ysis 
i ncl u des: 
•  Uri ne di pstic k i ncl u des: s pecific gra vit y, p H, pr otei n, bl o o d, ket o nes, bilir u bi n, 
ur o bili n o ge n, nitrite, a n d le u k oc yt e esterase 
•  Uri ne micr osc o p y i ncl u d es, b ut is n ot li mite d t o: detecti o n of f or m e d cell ul ar ele me nts, 
casts, bacteria, yeast, par asites, a n d cr ystals i n ce ntrif u ge d uri ne se di me nt. 
I n t he e ve nt of a b n or mal uri nal ysis fi n di n gs s us pici o us of uri nar y tract i nfecti o n, uri ne c ult ure 
s h o ul d be perf or m e d. P ositi ve uri ne c ult ure deter mi nati o n will be base d u p o n t he criteria of t he 
re p orti n g la b orat or y. 
If t he uri ne di pstic k is p ositi ve f or bl o o d, t he ce ntr al la b orat or y will perf or m refle xi ve testi n g t o 
i ncl u de micr osc o p y. A d diti o nal testi n g will be perf or me d acc or di n g t o t he j u d g me nt of t he 
I n v esti gat or. Referral t o ur ol o g y/ ur ol o gic e val uati o n is rec o m me n de d f or n e w or u ne x plai ne d 
cases of c o nfir me d h e mat uria ( ur ol o g y/ ur ol o gic e val uati o n is n ot re q uire d w here h e mat uria is 
c o nsi dere d t o be relate d t o dia betic ne p hr o p at h y). 
I n a d diti o n, uri ne al b u mi n, calci u m, gl uc ose, a n d creati ni ne will be assesse d as Bas eli ne ( Visit 3) 
a n d all s u bse q ue nt o n-sit e visits.  
Uri ne mar k ers of b o n e a n d calci u m meta b olis m will be assesse d at Baseli ne ( Visit 3), Wee k 2 6 
( Visit 9), a n d Wee k 7 9 ( Visit 1 3), a n d i ncl u de: calci u m a n d p h os p h or us. Se r u m mar kers of b o ne 
a n d calci u m meta b olis m are liste d i n Ta ble 2 . 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 5 9 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 5 9 
9. 2. 1. 4  Vit al si g n s a n d p h y si c al e x a m 
A c o m plete p h ysical e x a m (i ncl u di n g sitti n g bl o o d press ure a n d heart rate, te m perat ure a n d 
res pirat or y rate) will be perf or me d at Visit 1 ( Scree ni n g), Visit 9 ( Wee k 2 6), a n d Visit 1 3 
( Wee k 7 9). A b br e viate d p h ysical e x a ms (i ncl u di n g sitti n g bl o o d press ure an d heart rate) will be 
perf or me d at all ot her o n-site visits. T he a b bre viat e d p h ysical e x a m s h o ul d f oc us o n car diac a n d 
res pirat or y s yste ms, as w ell as a n y areas i m p orta nt f or assess me nt of A Es if necessar y. T hree 
se parat e seate d B Ps a n d heart r ate meas ure me nts s h o ul d be ta ke n wit h at least 1 mi n ute bet wee n 
meas ure me nts f oll o wi n g a 5- mi n ute rest peri o d, a n d pri or t o p hle b ot o m y. F ull details a n d 
directi o ns f or t he meas ure me nt of  bl o o d press ure are prese nte d i n A p p e n di x E . 
9. 2. 1. 5  El e ctr o c ar di o gr a m v ari a bl e s 
T he E C G assess me nt of “ n or mal” or “a b n or m al” will be a nal yze d. 
A 1 2-lea d E C G r ec or d is perf or me d l o call y at Scree ni n g ( Visit 1), Bas eli ne ( Visit 3), Wee k 2 6 
( Visit 9), a n d Wee k 7 9 ( Visit 1 3). 
T he 1 2-lea d E C G s h o ul d be perf or me d  after at least 1 0 mi n utes i n s u pi ne p ositi o n a n d pri or t o t he 
m or ni n g I M P a d mi nistrati o n. T he I n vesti gat or  s h o ul d re vie w t he E C G a n d d oc u me nt t he 
i nter pretati o n, si g n a n d d ate it o n t he E C G pri nt o ut a n d re p ort it i n t he e- C R F. Eac h E C G trace is 
a nal yz e d i n c o m paris o n wit h t he scree ni n g rec or d e d  trace. All ori gi nal traces are k e pt as s o urce 
data. 
N ote: A n y n e w E C G a b n or malit y s h o ul d be r ec hec ke d f or c o nfir mati o n a n d re p orte d as 
a p pr o priate f or t hat fi n di n g. 
9. 2. 1. 6  S elf- m o nit ori n g of bl o o d gl u c o s e 
A meter f or s elf- assess me nt of bl o o d gl uc os e will be  dis pe nse d at t he R u n-i n visit ( Visit 2). I n 
a d diti o n t o h o me meas ur e me nts of self- m o nit ore d bl o o d gl uc ose, s elf- m o nit ori n g of bl o o d gl uc ose 
will be perf or me d at Bas eli ne ( Visit 3) a n d all s u bse q ue nt o n-site visits. Gl uc ose meters us e d f or 
S M B G dis pla y res ults as plas ma gl uc os e c o n ce ntrati o n. 
Patie nts will als o recei ve a patie nt diar y at a ll o n-site visits wit h t he e x ce pti o n of F oll o w- u p 
Visit 1 4. T he diar y will be re vie w e d at all o n-site visits fr o m Visit 2 t o Visit 1 4 wit h t he e x ce pti o n 
of t he A B P M place me nts visits ( 3 A, 7 A, a n d 9 A). Self-assesse d bl o o d gl uc ose le vels will be 
e ntere d i n t he p atie nt diar y.  
Patie nts will be as ke d t o self-assess bl o o d gl uc ose levels at least 3 ti mes a wee k fr o m t he r u n-i n 
Visit ( Visit 2) t o t he e n d of t he Treat me nt Peri o d i ncl u di n g o n da y of eac h o n-site st u d y visit. 
After Visit 9 ( Wee k 2 6), if S M B G val ues are < 1 2 0 m g/ d L o ver a 2- w ee k p eri o d, t he I n vesti gat or 
ca n (at t heir o w n discreti o n) i nstr uct patie nts t o self- m o nit or bl o o d gl uc ose o nce a w ee k ( o n d a y 
of o n-site st u d y visit f or wee k s wit h o n-site st u d y visits). 
Patie nts will be re q ueste d t o self-assess bl o o d gl u c ose le vels i n t he faste d state a n d w he n e ver t h e y 
e x perie nce a n y ill nesses (e g, c ol d, fl u), or s y m pt o ms of h y per gl yce mia or h y p o gl yce mia. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 6 0 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 6 0 
S y m pt o ms of h y p o gl yce mia ma y i ncl u d e s ha ki ness,  dizzi ness, s weati n g, h u n ger, hea d ac h e, pale 
s ki n c ol or, s u d de n m o o di ness or beha vi or c ha n ges (s uc h as cr yi n g f or n o a p pare nt reas o n), cl u ms y 
or jer k y m o ve me nts, seiz ure, diffic ult y pa yi n g atte nti o n or c o nf usi o n, or ti n gli n g se nsati o ns 
ar o u n d t he m o ut h. Patie nts will be i nstr ucte d t o rec o r d t he prese nce or a bs e nce of h y p o gl yce mic 
e pis o des or h y p o gl yce mi c s y m pt o ms i n t he patie nt diar y pr o vi de d. 
Patie nts will als o be i nstr ucte d t o rec or d S M B G v al ues t hat are ≤7 0 m g/ d L ( ≤3. 9 m m ol/ L) i n t he 
patie nt diar y. Patie nts s h o ul d be i nstr ucte d t o c o nt act t he site if fasti n g S M B G val ues o v er 
3 c o nsec uti ve da ys are:  
•  > 2 7 0 m g/ d L ( 1 5. 0 m m ol/ L) fr o m Ra n d o mizati o n u p t hr o u g h t he s c he d ule d Wee k 8 Visit 
•  > 2 4 0 m g/ d L ( 1 3. 3 m m ol/ L) after t he Wee k 8 visit u p t hr o u g h t he s c he d ule d Wee k 1 2 Visit 
•  > 2 0 0 m g/ d L ( 1 1. 1 m m ol/ L) after t he Wee k 1 2 Vi sit a n d t hr o u g h t he e n d of t he 2 6- wee k 
d o u ble- bli n d Treat me nt Peri o d 
•  > 1 7 0 m g/ d L ( 9. 4 m m ol/ L) after t he Wee k 2 6 Visit t hr o u g h t he e n d of t he E xte nsi o n 
treat me nt peri o d 
9. 2. 1. 7  Di a b eti c k et o a ci d o si s 
Patie nts will be pr o vi de d wit h i nstr ucti o ns o n h o w t o rec o g nize t he s y m pt o ms of D K A a n d 
i nstr ucte d t o c o ntact t he site ( or see k e mer ge nc y m e dical ser vi ces if after b usi ness h o urs) if t hese 
s y m pt o ms de vel o p.  Patie nts s h o uld ha ve a f ull cli nical e val uati o n wit h la b orat or y testi n g f or 
p ossi ble D K A b y t h e i n vesti gat or or e mer ge nc y m e di cal ser vi ces p h ysicia n If s uc h e v al uati o n a n d 
la b orat or y testi n g c o nfir m t he prese nce of meta b olic aci d osis, t he n a p pr o priate treat me nt s h o ul d 
be i m ple me nte d a n d t he “ P ossi ble D K A” e- C R F s h o ul d be c o m plete d. See A p pe n di x D  f or f urt her 
details. 
9. 3  
O T H E R E N D P OI N T S 
9. 3. 1  P h ar m a c o ki n eti c s 
T he P K e n d p oi nt is: 
•  Plas ma c o nce ntr ati o ns of s ota glifl ozi n a n d its meta b olite pre- d ose at Wee k 4, 1 8, 2 6, 5 2, 
7 9 a n d 2 h o urs 3 0 mi n utes p ost- d ose at Wee k 2 6 a n d 7 9 
9. 3. 1. 1  S a m pli n g ti m e 
At Wee ks 4, 1 8, a n d 5 2 ( Visits 5, 8, a n d 1 1 res pecti v el y), P K sa m ples are t o be dra w n wit h t he 
ot her la b orat or y assess m e nts i m me diatel y bef ore  I M P a d mi nistrati o n. At Wee k 2 6 a n d Wee k 7 9 
( Visits 9 a n d 1 3, res pecti vel y), P K s a m ples sh o ul d be dra w n pre- d os e a n d 2 h o urs 3 0 mi n utes 
p ost- d ose, i m me diatel y after t he res pecti ve gl uc ose assess me nts d uri n g t he M M T T. 
P har mac o ki netic sa m ples ( wit h t he e x ce pti o n of t he 2 h o urs 3 0 mi n ute sa m ple d uri n g t he 
Wee k 2 6 a n d Wee k 7 9 M M T T) m ust  be c ollecte d bef ore a d mi nistrati o n of I M P. See Ta ble 3 f or 
t he i de ntificati o n of sa m ples. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 6 1 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 6 4 
patie nts wit h D B P > 8 0 m m H g.  Alt h o u g h effects o n B P i n P hase 2 data were o bser ve d wit h t he 
4 0 0 m g d ose at 1 2 wee ks, t he eff ects will be e x a mi ne d at Wee ks 1 2, 2 6, a n d 7 9. 
E vi de nce t hat s ota glifl ozi n re d uces ele vat e d S B P a n d D B P is descri be d i n S ecti o n  4. 5 . T o f urt her 
assess t hese effects, A B P M will be meas ure d i n a s u bset of patie nts wit h mea n S B P ≥1 3 0 m m H g 
at Scree ni n g, i n a d diti o n t o sitti n g B P meas ure d i n all patie nts. A B P M ma y re d uce t h e “ w hite 
c oat” effect see n wit h sitti n g bl o o d press ure m eas ure me nts, is m ore cl osel y c orrel ate d wit h 
mar kers of or ga n d a ma ge, a n d is a m ore se nsiti ve pre dict or of C V o utc o m es ( 1 2 ). It als o per mits 
assess me nt of ni g htti me a n d da yti me bl o o d press ure ( 1 2 ). 
E n d p oi nts f or e val uati n g re nal f u n cti o n i ncl u de e G F R, base d o n ser u m creati ni ne, a n d uri ne 
al b u mi n t o creati ni ne rati o as well as r o uti ne m o nit ori n g of uri ne via di pstic k a n d micr osc o p y.  
U G E, uri ne G C R ar e ot h er vali d mar k ers of re na l f u ncti o n, a n d will be assesse d at a p pr o pri ate 
ti me p oi nts i n t his st u d y. 
Bec a use of p ot e ntial eff e cts o n b o ne a n d calci u m meta b olis m, s pecific bi o mar kers f or b o ne a n d 
calci u m meta b olis m will be assesse d at re g ular ti me p oi nts. I n vie w of t he S G L T 1 i n hi bit or y 
effects i n t he GI tract, s p ecific mar kers of i ntesti n al tra nsit a n d a bs or pti o n will als o be meas ure d. 
T he ot her efficac y a n d s afet y assess me nts i n  t his st u d y are sta n dar d, well-esta blis he d 
meas ure me nts f or a P has e 3 st u d y e val uati n g t he treat me nt of T 2 D i n a d ult patie nts.  
T he le n gt h of t he st u d y is c o ns i dere d a p pr o priat e f or detecti o n of t he pri mar y e n d p oi nt gi ve n t he 
p o wer esti mates (s ee Secti o n  1 1 ). 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 6 5 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 6 5 
1 0  
S T U D Y P R O C E D U R E S 
1 0. 1  VI SI T S C H E D U L E 
T he visit sc he d ule a n d pr oce d ures/ assess me nts are liste d i n t he “ St u d y Fl o w C hart” (Secti o n  1. 2 ). 
T he ai m of t his secti o n is t o pr o vi de details o n h o w s o me of t he pr o ce d ures /assess me nts s h o ul d be 
perf or me d. 
T his is a n o ut- patie nt st u d y a n d c o nsists of 1 4 o n- site visits ( 1 7 o n-site visits f or patie nts e nr olle d 
i n t he A B P M s u bst u d y), alt h o u g h o pti o nal o n-site a n d/ or tele p h o ne visits ca n be sc he d ul e d at a n y 
ti me f or a n y reas o n d uri n g t he st u d y w h e ne ver c o nsi dere d necessar y b y t he I n v esti gat or. 
T he patie nts nee d t o b e f asti n g f or o n-site visits Visit 1 t hr o u g h Visit 1 3 ( Wee k - 4 t hr o u g h 
Wee k 7 9), u nless i nstr ucte d ot her wise b y t he I n vesti gat or. T hr o u g h o ut t he st u d y, “fasti n g” is 
defi ne d as 8 h o urs wit h o ut f o o d. N ote:  If t he p atie nt is n ot fasti n g at t he visits s pecifie d a b o ve, t he 
bl o o d sa m ple will n ot be c ollecte d  a n d a ne w a p p oi nt me nt s h o ul d be gi ve n t o t he patie nt f or t he 
f oll o wi n g da y if p ossi ble, wit h i nstr ucti o n t o be faste d. Patie nts i n t he A B P M s u bst u d y d o n ot 
nee d t o be f asti n g f or visits Visit 3 A, Visit 7 A, a n d Visit 9 A, d uri n g w hic h A B P M de vice 
place me nt will occ ur. 
T he R u n-i n visit ( Visit 2) ca n be p erf or m e d as s o o n as t he res ults of all scree ni n g tests are 
a vaila ble a n d t he patie nt is c o nfir me d t o be eli gi ble f or partici pati o n i n t he st u d y. T he visit 
wi n d o w f or Visit 4 t hr o u g h Visit 9, a n d Visit 1 4 s h o ul d occ ur wit hi n ± 3 da ys. Visits 1 0, 1 1 a n d 
1 2 s h o ul d occ ur wit hi n ± 7 da ys. Visit 1 3 ( E O T) s h o ul d occ ur d uri n g D a y 5 4 8 t o 5 5 5. F or F oll o w-
u p Visit V 1 4, t he visit wi n d o w s h o ul d occ ur wit hi n +  3 da ys, 4 wee ks aft er Visit 1 3. F or patie nts 
i n t he A B P M s u bst u d y, t he Visits 3 A, 7 A, a n d 9 A s h o ul d occ ur wit hi n ± 2 da ys. 
If o ne visit date is c ha n ge d, t he ne xt visit s h o uld occ ur acc or di n g t o t he ori gi nal sc he d ul e, ie 
calc ulate d fr o m t he date of Bas eli ne visit ( Visit 3, Wee k 0). 
F or a c o m plete list of pr o ce d ures s c he d ule d f or eac h st u d y visit please refer t o t he St u d y Fl o w 
C hart ( Secti o n  1. 2 ), w hic h details t he pr oce d ures t o be perf or me d. 
All data o btai ne d d uri n g t he trial visits are re vie w e d b y t h e I n vesti gat or a n d s u b-i n vesti gat ors w h o 
are q ualifi e d i n treat me nt of T 2 D a n d are trai ne d o n t he st u d y. 
1 0. 1. 1 S cr e e ni n g P eri o d 
T he Scree ni n g p eri o d is u p t o 4 wee ks a n d i ncl u d es t he Scree ni n g p h ase a n d t he R u n-i n p hase. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 6 6 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 6 7 
•  Meas ure me nt of b o d y hei g ht a n d w ei g ht 
•  C o m plete p h ysical e x a mi nati o n i ncl u di n g vita l si g ns ( S B P a n d D B P, te m perat ure, h eart 
rate, a n d res pirat or y rate). T hree se p arate seat e d B Ps a n d heart rate meas ure me nts s h o ul d 
be ta ke n wit h at least 1 mi n ute bet wee n me as ure m e nts f oll o wi n g a 5- mi n ute rest peri o d, 
a n d pri or t o p hle b ot o m y (see A p p e n di x E  f or details of B P pr oce d ure) 
•  1 2-lea d E C G 
•  T he f oll o wi n g l a b orat or y testi n g ( b y t he ce ntral la b orat or y): 
- 
Fasti n g plas ma gl uc ose 
- 
H b A 1c 
- 
He patitis ser ol o g y 
- 
Ser u m pre g na n c y testi n g f or W O C B P 
- 
ser u m F S H a n d estra di ol (p ost me n o pa usal w o me n o nl y) 
- 
He mat ol o g y 
- 
Cli nical c he mistr y t o i ncl u de a m yl ase a n d li pas e 
- 
Fasti n g li pi ds 
- 
Uri nal ysis ( di pstic k a n d micr osc o p y) 
•  Patie nts are i nstr ucte d t o ret ur n t o t he site f or Visit 2 ( Wee k - 2) i n a faste d state 
1 0. 1. 1. 2 R u n-i n p h a s e 
T he R u n-i n p hase is 2 wee ks a n d i ncl u des Visit 2 ( Wee k - 2) a n d, f or patie nts w h o c o nse nte d t o 
t he A B P M s u bst u d y, Visit 3 A ( W ee k - 1).  
1 0. 1. 1. 2. 1 O n- sit e Vi sit 2 ( R u n-i n, W e e k - 2) 
T he f oll o wi n g pr oce d ures/assess me nts will be perf or me d at Visit 2 ( Wee k - 2): 
•  Meas ure me nt of b o d y wei g ht 
•  A b bre viate d p h ysical e x a mi nati o n i ncl u di n g vital si g ns perf or me d after t he patie nt has 
bee n seat e d f or at least 5 mi n utes ( S B P a n d D B P, a n d heart rate). Bl o o d press ure a n d h eart 
rate will be assess e d 3 ti mes wit h at least 1 mi n ute bet wee n eac h meas ure me nt (see 
A p pe n di x E  f or details) 
•  Diet a n d e x ercise i nstr ucti o n 
•  Bl o o d gl uc ose meter is dis pe nse d a n d i nstr ucti o ns/trai ni n g are pr o vi d e d 
•  I nstr u cti o n o n basic G U h y gie n e a n d h y drati o n (see A p pe n di x D ) 
•  I R T t o be n otifie d 
•  Patie nt diar y is c ollecte d/re vie we d. A ne w di ar y,  i ncl u di n g h y p o gl yce mia l o g, is dis pe nse d 
a n d i nstr ucti o ns/trai ni n g are pr o vi d e d as nee de d 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 6 8 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 6 8 
•  A Es/ S A Es/ A E SI/ E O SI a n d h y p o gl yce mia (if a n y) are re p orte d, i ncl u di n g t h ose occ urri n g 
si nce Visit 1 
•  R u n-i n kit/ place b o is dis pe nse d  
•  C o nc o mita nt me dicati o n 
•  Fasti n g S M B G is assess e d 
•  Patie nts are i nstr ucte d t o ret ur n t o t he site i n t he fasti n g state f or Visit 3 ( Ra n d o mizati o n) 
or, f or patie nts e nr olle d i n t he A B P M s u bst u d y, at Visit 3 A 
1 0. 1. 1. 2. 2 A m b ul at or y bl o o d pr e s s ur e m o nit or pl a c e m e nt o n- sit e vi sit 3 A, ( W e e k - 1) 
T he f oll o wi n g pr oce d ures will be perf or me d at t hese visits o nl y f or p atie nts i n t he A B P M 
s u bst u d y: 
•  Place me nt of t he A B P M de vice 
Patie nts d o n ot nee d t o be fasti n g f or Visit 3 A. After t he patie nt has w or n t he A B P M de vice f or 
2 4 h o urs after pl ace m e nt, t he y will re m o v e it a n d p ost it t o t he i n vesti gati ve site usi n g a p pr o priate 
pac ka gi n g pr o vi de d b y t h e site. Data will be re vie we d t o assess q ualit y; p atie nts wit h A B P M data 
n ot of s ufficie nt q ualit y s h o ul d n ot be ra n d o mize d  u ntil t he Baseli ne A B P M rec or di n g h as bee n 
re peat e d (see A p pe n di x B ). 
1 0. 1. 2 D o u bl e- bli n d r a n d o mi z e d C or e Tr e at m e nt P eri o d 
1 0. 1. 2. 1 Tr e at m e nt P eri o d ( D a y 1 t o W e e k 2 6) 
U p o n s uccessf ul c o m pleti o n of t he R u n-i n p hase, patie nts will be ra n d o ml y all ocate d t o eit her 
s ota glifl ozi n 4 0 0 m g or place b o f or t he d o u ble- bli n d treat me nt peri o d lasti n g 2 6 w ee ks. All 
ra n d o mize d patie nts will be f oll o we d at re g ular o n-site visits f or t he d urati o n of t he treat me nt 
peri o d. 
I n a d diti o n t o r o uti ne la b orat or y testi n g, t h e f oll o wi n g will be perf or me d at s pecifie d ti me p oi nts: 
plas ma c o nce ntrati o n; mar kers of  i ntesti nal tra nsit a n d a bs or ptio n; mar kers of b o ne a n d calci u m 
meta b olis m; uri ne al b u mi n, calci u m, gl u c ose, a n d creati ni ne. 
T he date a n d ti me of t he last i nta ke of I M P pri or t o visits w her e P K sa m ples are ta k e n s h o ul d be 
rec or d e d b y t he patie nt i n t he patie nt diar y. Patients s h o ul d be re mi n de d of t h is at visits prece di n g 
P K ti me p oi nts t o e ns ure t hese details are ca pt ure d. 
I n t he e ve nt of a b n or mal uri nal ysis fi n di n gs s us pici o us of uri nar y tract i nfecti o n, uri ne c ult ure 
s h o ul d be perf or m e d. P ositi ve uri ne c ult ure deter mi nati o n will be base d u p o n t he criteria of t he 
re p orti n g la b orat or y. 
I n a d diti o n, P P G will be assesse d at Baseli ne a n d 2 h o urs after c o ns u mi n g a sta n dar d mi x e d li q ui d 
brea kf ast meal vial a M M T T o n Da y 1 a n d at Wee k 2 6. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 6 9 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 6 9 
F or patie nts w h o h a ve c o nse nte d t o t he A B P M s u bst u d y, t here will be 2 a d diti o nal o n-site visits 
f or place me nt of t he A B P M de vice, w hic h will occ ur at Da y 8 3 ( Visit 7 A) a n d Da y 1 8 1 
( Visit 9 A). Pr oce d ur es f or Visits 7 A a n d 9 A are s p ecifie d i n Secti o n  1 0. 1. 2. 2 . 
1 0. 1. 2. 1. 1 O n- sit e R a n d o mi z ati o n Vi sit o n D a y 1 ( B a s eli n e; W e e k 0; Vi sit 3) 
T he f oll o wi n g pr oce d ures will be perf or me d at t his visit: 
•  E x cl usi o n criteria are t o be re vie w e d, i ncl u di n g assess me nt of c o m plia nce d uri n g R u n-i n 
p hase 
•  C o nc o mita nt me dicati o ns are ass esse d 
•  Meas ure me nt of b o d y wei g ht 
•  A b bre viate d p h ysical e x a mi nati o n i ncl u di n g vital si g ns perf or me d after t he patie nt has 
bee n seat e d f or at least 5 mi n utes. S yst olic a n d di ast olic B P a n d heart rate will be assesse d 
3 ti mes wit h at least 1 mi n ute bet wee n eac h meas ure me nt (see A p pe n di x E  f or details) 
•  I M P acc o u nti n g a n d c o m plia nce f or si n gle- bli n d place b o R u n-i n p hase 
•  I R T t o be n otifie d a n d ra n d o mizati o n will occ ur 
•  A Es/ S A Es/ A E SI/ E O SI a n d h y p o gl yce mia (if a n y) are re p orte d 
•  Diet a n d e x ercise i nstr ucti o n 
•  Patie nt diar y, i ncl u di n g h y p o gl yce mia l o g,  is c ollecte d/re vie we d a n d dis pe nse d a n d 
i nstr ucti o ns/trai ni n g ar e pr o vi de d as nee de d  
•  I nstr u cti o n o n D K A s y m pt o ms (see A p pe n di x D ) is pr o vi de d 
•  I nstr u cti o n o n basic G U h y gie n e a n d h y drati o n (see A p pe n di x D ) 
•  1 2-lea d E C G, pri or t o I M P a d mi nistrati o n 
•  Fasti n g S M B G is assess e d 
•  Sta n dar d M M T T ( 2- h o ur p ost pra n dial gl u c ose meas ure me nts) 
•  T he f oll o wi n g l a b orat or y testi n g ( b y t he ce ntral la b orat or y): 
- 
Fasti n g plas ma gl uc ose 
- 
H b A 1c 
- 
Uri ne pre g n a nc y testi n g f or W O C B P (a n y p ositi ve uri ne test res ults m ust be c o nfir me d 
b y a s er u m pr e g na nc y test) 
- 
He mat ol o g y 
- 
Cli nical c he mistr y t o i ncl u de a m yl ase a n d li pas e 
- 
Fasti n g li pi ds 
- 
Uri nal ysis ( di pstic k a n d micr osc o p y) 
- 
Uri ne a nal ysis f or al b u mi n, calci u m, gl uc ose, a n d creati ni ne 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 7 0 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 7 0 
•  A d diti o nal la b orat or y testi n g at t his visit: 
- 
Mar kers of i ntesti nal tra nsit a n d a bs or p ti o n ( vita mi ns B 6, B 1 2, K, E, a n d A, ser u m 
f olate, a n d ferriti n) 
- 
Mar kers of b o ne a n d calci u m meta b olis m (ser u m a n d uri nar y calci u m, ser u m 
2 5- h y dr o x y vita mi n D, ser u m 1, 2 5- di h y dr o x y vita mi n D, ser u m a n d uri nar y 
p h os p h or us, ser u m P T H, mar kers of b o n e res or pti o n [ser u m N T X, ser u m β - C T X- 1], 
a n d b o ne f or m ati o n [ser u m P 1 N P]) 
 
 
 
 
•  I M P is dis pe nse d 
•  Patie nts are i nstr ucte d t o ret ur n t o t he site i n t he fasti n g state f or Visit 4 ( Wee k 1). 
•  F or acc o u nta bilit y a n d c o m plia nce p ur p oses, patie nt s are i nstr ucte d t o ret ur n t o t he site 
wit h t heir i n- use b ottle(s) dis pe nse d d uri n g Visit 3. 
1 0. 1. 2. 1. 2 O n- sit e vi sit s at W e e k s 1, 4, 8, 1 2, a n d 1 8 ( Vi sit s 4 t o 8) 
T he f oll o wi n g will be perf or me d at t hese visits: 
•  Re m o val of A B P M de vic e ( o nl y at Wee k 1 2 [ Visit 7] a n d o nl y f or p atie nts i n t he A P B M 
s u bst u d y) 
•  I R T t o be n otifie d (all visits e x ce pt Visit 4) 
•  I M P acc o u nti n g a n d c o m plia nce 
•  Patie nt diar y, i ncl u di n g h y p o gl yce mia l o g,  is c ollecte d/re vie we d a n d dis pe nse d a n d 
i nstr ucti o ns/trai ni n g ar e pr o vi de d as nee de d 
•  C o nc o mita nt me dicati o ns are ass esse d 
•  A Es/ S A Es/ A E SI/ E O SI a n d h y p o gl yce mia (if a n y) are re p orte d 
•  Patie nts are e v al uate d f or gl yce mic res c ue (s ee Secti o n  9. 1. 4. 7 ) 
•  Meas ure me nt of b o d y wei g ht 
•  A b bre viate d p h ysical e x a mi nati o n i ncl u di n g vital si g ns perf or me d after t he patie nt has 
bee n seat e d f or at least 5 mi n utes. S yst olic a n d di ast olic B P a n d heart rate will be assesse d 
3 ti mes wit h at least 1 mi n ute bet wee n eac h meas ure me nt (see A p pe n di x E  f or details) 
•  I nstr u cti o n o n D K A s y m pt o ms (see A p pe n di x D ) is pr o vi de d 
•  I nstr u cti o n o n basic G U h y gie n e a n d h y drati o n (see A p pe n di x D ) 
•  Fasti n g S M B G is assess e d 
•  T he f oll o wi n g l a b orat or y testi n g ( b y t he ce ntral la b orat or y): 
- 
Fasti n g plas ma gl uc ose (f or all visits) 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 7 1 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 7 1 
- 
H b A 1c (all visits e x ce pt Visit 4) 
- 
Uri ne pre g n a nc y testi n g f or W O C B P (all visits e x ce pt Visit 4; a n y p ositi ve uri ne test 
res ults m ust be c o nfir me d b y a s er u m pre g na nc y t est) 
- 
He mat ol o g y ( Visit 7 o nl y) 
- 
Cli nical c he mistr y t o i ncl u de a m yl ase a n d li pas e ( Visits 5, 6, 7, a n d 8) 
- 
Fasti n g li pi ds (all visits e x ce pt Visit 4) 
- 
Uri ne a nal ysis f or al b u mi n, calci u m, gl uc ose, a n d creati ni ne (f or all visits) 
•  Pre- d ose plas ma c o nce ntrati o n sa m ples are c ollect e d a n d se nt t o t he a p pr o priate la b orat or y 
( Visits 5 a n d 8 o nl y) 
•  Patie nts s h o ul d be re mi n de d t o r ec or d t he ti me of I M P i nta ke o n t he d a y bef ore t heir n e xt 
visit (re mi n ders at Visits 4, 7 a n d 8 o nl y) 
•  I M P is dis pe nse d (all visits e x ce pt Visit 4) 
•  Patie nts are i nstr ucte d t o ret ur n t o t he site i n t he fasti n g state f or t h eir ne xt visit. 
•  F or acc o u nta bilit y a n d c o m plia nce p ur p oses, patie nt s are i nstr ucte d t o ret ur n t o t he site 
wit h t heir b ottle(s) at t he ne xt visit 
N B: F or patie nts i n t he A B P M s u bst u d y, it is n ot re q uire d t o ret ur n t h eir b ottle(s) at 
A B P M visits). 
1 0. 1. 2. 1. 3 O n- sit e Vi sit 9 at W e e k 2 6  
T he f oll o wi n g will be perf or me d at t his visit: 
•  Re m o val of A B P M de vic e ( o nl y f o r patie nts i n t he A P B M s u bst u d y) 
•  I R T t o be n otifie d 
•  I M P acc o u nti n g a n d c o m plia nce  
•  Patie nt diar y, i ncl u di n g h y p o gl yce mia l o g,  is c ollecte d/re vie we d a n d dis pe nse d a n d 
i nstr ucti o ns/trai ni n g ar e pr o vi de d as nee de d 
•  C o nc o mita nt me dicati o ns are ass esse d 
•  A Es/ S A Es/ A E SI/ E O SI a n d h y p o gl yce mia (if a n y) are re p orte d 
•  Patie nts are e v al uate d f or gl yce mic res c ue (s ee Secti o n  9. 1. 4. 7 ) 
•  Meas ure me nt of b o d y wei g ht 
•  C o m plete p h ysical e x a mi nati o n i ncl u di n g vita l si g ns ( S B P a n d D B P, te m perat ure, h eart 
rate, a n d res pirat or y rate). T hree se p arate seat e d B Ps a n d heart rate meas ure me nts s h o ul d 
be ta ke n wit h at least 1 mi n ute bet wee n me as ure m e nts f oll o wi n g a 5- mi n ute rest peri o d, 
a n d pri or t o p hle b ot o m y (see A p p e n di x E  f or details of B P pr oce d ure)  
•  Diet a n d e x ercise i n str ucti o n is pr o vi de d 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 7 2 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 7 2 
•  I nstr u cti o n o n D K A s y m pt o ms (see A p pe n di x D ) is pr o vi de d 
•  I nstr u cti o n o n basic G U h y gie n e a n d h y drati o n (see A p pe n di x D ) 
•  1 2-lea d E C G, pri or t o t he m or ni n g I M P a d mi nistrati o n 
•  Fasti n g S M B G is assess e d 
•  Sta n dar d M M T T ( 2- h o ur p ost pra n dial gl u c ose meas ure me nts) 
•  T he f oll o wi n g l a b orat or y testi n g ( b y t he ce ntral la b orat or y): 
- 
Fasti n g plas ma gl uc ose 
- 
H b A 1c 
- 
Uri ne pre g n a nc y testi n g f or W O C B P (a n y p ositi ve uri ne test res ults m ust be c o nfir me d 
b y a s er u m pr e g na nc y test) 
- 
He mat ol o g y 
- 
Cli nical c he mistr y t o i ncl u de a m yl ase a n d li pas e 
- 
Fasti n g li pi ds 
- 
Uri nal ysis ( di pstic k a n d micr osc o p y) 
- 
Uri ne a nal ysis f or al b u mi n, calci u m, gl uc ose, a n d creati ni ne 
•  A d diti o nal la b orat or y testi n g at t his visit: 
- 
Mar kers of i ntesti nal tra nsit a n d a bs or p ti o n ( vita mi ns B 6, B 1 2, K, E, a n d A, ser u m 
f olate, a n d ferriti n) 
- 
Mar kers of b o ne a n d calci u m meta b olis m (ser u m a n d uri nar y calci u m, ser u m 
2 5- h y dr o x y vita mi n D, ser u m 1, 2 5- di h y dr o x y vita mi n D, ser u m a n d uri nar y 
p h os p h or us, ser u m P T H, mar kers of b o n e res or pti o n [ser u m N T X, ser u m β - C T X- 1], 
a n d b o ne f or m ati o n [ser u m P 1 N P]) 
 
 
•  Plas ma c o nce ntrati o n sa m ples ( pre- d os e a n d 2 h o urs 3 0 mi n utes p ost- d ose) are c ollecte d 
a n d se nt t o t he a p pr o pri ate la b orat or y 
•  I M P is dis pe nse d 
•  Patie nts are i nstr ucte d t o ret ur n t o t he site i n t he fasti n g state i n 1 3 wee ks f or Visit 1 0. 
•  F or acc o u nta bilit y a n d c o m plia nce p ur p oses, patie nt s are i nstr ucte d t o ret ur n t o t he site 
wit h t heir b ottle(s) at Visit 1 0. 
1 0. 1. 2. 2 A m b ul at or y bl o o d pr e s s ur e m o nit or pl a c e m e nt o n- sit e Vi sit 7 A a n d 9 A ( W e e k 1 2 
a n d W e e k 2 6) 
T he f oll o wi n g pr oce d ures will be perf or me d at t hese visits o nl y f or p atie nts i n t he A B P M 
s u bst u d y: 
•  
Place me nt of t he A B P M de vice 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 7 3 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 7 3 
•  
Patie nts are i nstr ucte d t o ret ur n t o t he site i n a fasti n g state i n 2 4 h o urs 
•  
Patie nts s h o ul d be re mi n de d t o rec or d t he ti me of I M P i nta ke o n t he d a y bef ore Visit 9 
(re mi n der at Visit 9 A o nl y). 
1 0. 1. 3 D o u bl e- bli n d e xt e n si o n p eri o d 
U p o n c o m pleti o n of t he d o u ble- bli n d c ore treat m e nt peri o d, patie nts will re mai n o n t he sa me 
bli n de d treat me nt t hr o u g h o ut a 5 3- wee k d o u ble- bli n d e xte nsi o n peri o d f or a t otal treat me nt 
d urati o n of 7 9 wee ks. 
T he d o u ble- bli n d e xte nsi o n peri o d will c o nsist of  4 visits, occ urri n g at Wee k 3 9 ( Visit 1 0), 
Wee k 5 2 ( Visit 1 1), Wee k 6 5 ( Visit 1 2), a n d a n e n d- of-treat me nt visit at Wee k 7 9 ( Visit 1 3). 
I n t he e ve nt of a b n or mal uri nal ysis fi n di n gs s us pici o us of uri nar y tract i nfecti o n, uri ne c ult ure 
s h o ul d be perf or m e d. P ositi ve uri ne c ult ure deter mi nati o n will be base d u p o n t he criteria of t he 
re p orti n g la b orat or y. 
1 0. 1. 3. 1 O n- sit e vi sit s at W e e k s 3 9, 5 2, a n d 6 5 ( Vi sit s 1 0 t o 1 2) 
T he f oll o wi n g will be perf or me d at t hese visits: 
•  I R T t o be n otifie d 
•  I M P acc o u nti n g a n d c o m plia nce 
•  Patie nt diar y, i ncl u di n g h y p o gl yce mia l o g,  is c ollecte d/re vie we d a n d dis pe nse d a n d 
i nstr ucti o ns/trai ni n g ar e pr o vi de d as nee de d 
•  C o nc o mita nt me dicati o ns are ass esse d 
•  A Es/ S A Es/ A E SI/ E O SI a n d h y p o gl yce mia (if a n y) are re p orte d 
•  Patie nts are e v al uate d f or gl yce mic res c ue (s ee Secti o n  9. 1. 4. 7 ) 
•  Meas ure me nt of b o d y wei g ht 
•  A b bre viate d p h ysical e x a mi nati o n i ncl u di n g vital si g ns perf or me d after t he patie nt has 
bee n seat e d f or at least 5 mi n utes. S yst olic a n d di ast olic B P a n d heart rate will be assesse d 
3 ti mes wit h at least 1 mi n ute bet wee n eac h meas ure me nt (see A p pe n di x E  f or details) 
•  Diet a n d e x ercise i nstr ucti o n is pr o vi de d ( Visit 1 1 o nl y) 
•  I nstr u cti o n o n D K A s y m pt o ms (see A p pe n di x D ) is pr o vi de d 
•  I nstr u cti o n o n basic G U h y gie n e a n d h y drati o n (see A p pe n di x D ) 
•  Fasti n g S M B G is assess e d 
•  T he f oll o wi n g l a b orat or y testi n g ( b y t he ce ntral la b orat or y): 
- 
Fasti n g plas ma gl uc ose 
- 
H b A 1c 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 7 4 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 7 4 
- 
Uri ne pre g n a nc y testi n g f or W O C B P (a n y p ositi ve uri ne test res ults m ust be c o nfir me d 
b y a s er u m pr e g na nc y test) 
- 
He mat ol o g y 
- 
Cli nical c he mistr y t o i ncl u de a m yl ase a n d li pas e 
- 
Uri ne a nal ysis f or al b u mi n, calci u m, gl uc ose, a n d creati ni ne 
•  Pre- d ose plas ma c o nce ntrati o n sa m ples are c ollect e d a n d se nt t o t he a p pr o priate la b orat or y 
( Visit 1 1 o nl y)  
•  Patie nts s h o ul d be re mi n de d t o r ec or d t he ti me of I M P i nta ke o n t he d a y bef ore t heir n e xt 
visit ( Visits 1 0 a n d 1 2 o nl y) 
•  I M P is dis pe nse d 
•  Patie nts are i nstr ucte d t o ret ur n t o t he site i n t he fasti n g state f or t h eir ne xt visit. 
•  F or acc o u nta bilit y a n d c o m plia nce p ur p oses, patie nt s are i nstr ucte d t o ret ur n t o t he site 
wit h t heir b ottle(s) at t he ne xt visit. 
1 0. 1. 3. 2 O n- sit e Vi sit 1 3 at W e e k 7 9 - E n d- of-tr e at m e nt 
T he f oll o wi n g will be perf or me d at t his visit: 
•  I R T t o be n otifie d (if E O T visit is als o last visit, I R T s h o ul d be n otifie d f or e n d of st u d y) 
•  I M P acc o u nti n g a n d c o m plia nce 
•  Patie nt diar y, i ncl u di n g h y p o gl yce mia l o g,  is c ollecte d/re vie we d a n d dis pe nse d a n d 
i nstr ucti o ns/trai ni n g ar e pr o vi de d as nee de d 
•  C o nc o mita nt me dicati o ns are ass esse d 
•  A Es/ S A Es/ A E SI/ E O SI a n d h y p o gl yce mia (if a n y) are re p orte d 
•  Patie nts are e v al uate d f or gl yce mic res c ue (s ee Secti o n  9. 1. 4. 7 ) 
•  Meas ure me nt of b o d y wei g ht 
•  C o m plete p h ysical e x a mi nati o n i ncl u di n g vita l si g ns ( S B P a n d D B P, te m perat ure, h eart 
rate, a n d res pirat or y rate). T hree se p arate seat e d B Ps a n d heart rate meas ure me nts s h o ul d 
be ta ke n wit h at least 1 mi n ute bet wee n me as ure m e nts f oll o wi n g a 5- mi n ute rest peri o d, 
a n d pri or t o p hle b ot o m y (see A p p e n di x E  f or details of B P pr oce d ure) 
•  Diet a n d e x ercise i n str ucti o n is pr o vi de d 
•  I nstr u cti o n o n D K A s y m pt o ms (see A p pe n di x D ) is pr o vi de d 
•  I nstr u cti o n o n basic G U h y gie n e a n d h y drati o n (see A p pe n di x D ) 
•  1 2-lea d E C G, pri or t o t he m or ni n g I M P a d mi nistrati o n 
•  Fasti n g S M B G is assess e d 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 7 5 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 7 6 
•  A Es/ S A Es/ A E SI/ E O SI a n d h y p o gl yce mia (if a n y) are re p orte d 
•  Meas ure me nt of b o d y wei g ht  
•  A b bre viate d p h ysical e x a mi nati o n i ncl u di n g vital si g ns perf or me d after t he patie nt has 
bee n seat e d f or at least 5 mi n utes. S yst olic a n d di ast olic B P a n d heart rate will be assesse d 
3 ti mes wit h at least 1 mi n ute bet wee n eac h meas ure me nt (see A p pe n di x E  f or details) 
•  Scree ni n g a n d c urr e nt B P rea di n gs are re vie we d, a n d p osttreat me nt a nti h y perte nsi ve 
me dicati o n is a d de d or a dj uste d as per i nstr ucti o ns gi ve n i n Secti o n  8. 9.  
•  S M B G is perf or m e d 
•  T he f oll o wi n g l a b orat or y testi n g ( b y t he ce ntral la b orat or y): 
- 
cli nical c he mistr y t o i ncl u de a m yl ase a n d li pas e 
- 
uri ne a nal ysis f or al b u mi n, calci u m, gl uc ose, a n d creati ni ne 
•  A d diti o nal la b orat or y testi n g at t his visit: 
- 
Mar kers of i ntesti nal tra nsit a n d a bs or p ti o n ( vita mi ns B 6, B 1 2, K, E, a n d A, ser u m 
f olate, a n d ferriti n) 
•  T he patie nt is i nstr ucte d t o sc he d ule f ut ure  f oll o w- u p wit h t heir o w n pers o n al p h ysicia n. 
1 0. 2  
D E FI NI TI O N O F S O U R C E D A T A 
1 0. 2. 1 S o ur c e d at a t o b e f o u n d i n p ati e nt’ s fil e 
E val uati o ns rec or de d i n t he e- C R F m ust be  s u p p orte d b y a p pr o priat el y si g n e d s o urce 
d oc u me ntati o n relate d b ut n ot li mite d t o t he f oll o wi n g: 
•  A gree me nt a n d si g n at ure of I C F wit h t he st u d y i de ntificati o n 
•  St u d y i d e ntificati o n ( na m e) 
•  Patie nt n u m ber, c o nfir mati o n of ra n d o mizati o n, treat me nt batc h n u m ber, d ates a n d d oses 
of st u d y me dicati o n a d mi nistrati o n 
•  Me dical, s ur gical, dia b et es hist or y, i ncl u di n g i nf or mati o n o n: 
- 
De m o gra p h y, i ncl usi o n a n d e x cl usi o n criteria 
- 
Last p artici pati o n i n a cli nical trial 
- 
C o ntrace pti o n met h o d f or W O C B P 
- 
Pre vi o us a n d c o nc o mita nt me dicati o n 
•  Dates a n d ti mes of visits a n d assess me nts i ncl u di n g e x a mi nati o n res ults 
•  Vital si g ns, hei g ht, b o d y wei g ht, la b orat or y re p orts, I n v esti gati o n res ults (e g, E C G traces, 
i ma gi n g re p orts) 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 7 7 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 7 7 
•  A d verse e ve nts a n d f oll o w- u p: 
- 
I n case of S A E, t he site s h o ul d file i n t he s o urce d oc u me nts at least c o pies of t he 
h os pitalizati o n re p orts a n d a n y rele v a nt e x a mi nati o n re p orts d oc u me nti n g t he 
f oll o w- u p of t he S A E. 
•  Date of pr e mat ure treat m e nt di sc o nti n uati o n (if a n y) a n d reas o n 
•  Date of pr e mat ure st u d y disc o nti n uati o n (if a n y) a n d reas o n 
•  N ursi n g n otes 
•  Dieticia n’s n otes 
•  P h ysicia n’s n otes. 
1 0. 2. 2 S o ur c e d at a v erifi c ati o n r e q uir e m e nt s f or s cr e e n f ail ur e s 
F or scree n fail ure p atie nts, t he f oll o wi n g s o urce d ata m ust be verifie d: p atie nt's i de ntificati o n 
details, t he i nf or me d c o nse nt si g ne d b y t he p atie nt, t he st u d y i de ntificati o n ( na me), d ates of st u d y 
visits a n d t he mai n reas o ns f or scree n fail ure. 
1 0. 3  
H A N D LI N G O F P A TI E N T T E M P O R A R Y O R P E R M A N E N T T R E A T M E N T 
DI S C O N TI N U A TI O N A N D O F P A TI E N T S T U D Y DI S C O N TI N U A TI O N  
T he I M P s h o ul d be c o nti n ue d w he ne v er p ossi bl e. I n case t h e I M P is st o p pe d, it s h o ul d be 
deter mi ne d w het h er t he st o p ca n be ma d e te m p or aril y; per m a ne nt I M P disc o nti n uati o n s h o ul d be 
a last res ort. A n y I M P disc o nti n uati o n s h o ul d be f ull y d oc u me nte d i n t he e- C R F. I n a n y case, t he 
patie nt s h o ul d re mai n i n t he st u d y a n d f oll o we d f or t he re mai n d er of t he st u d y d urati o n t o c ollect 
vital safet y stat us  a n d e n d p oi nt data. 
1 0. 3. 1 T e m p or ar y tr e at m e nt di s c o nti n u ati o n wit h i n v e sti g ati o n al m e di ci n al pr o d u ct( s) 
Te m p orar y tr eat me nt dis c o nti n uati o n ma y b e c o nsi dere d b y t he I n v esti gat or beca us e of s us pecte d 
A Es. L o wer e xtre mit y c o m plicati o ns (s uc h as s k i n ulcers, i nfecti o n, oste o m yelitis, a n d ga n gre ne) 
re q uiri n g treat me nt s h o ul d lea d t o te m p orar y disc o nti n uati o n of I M P. Rei nitiati n g treat me nt wit h 
t he I M P will be d o ne u n d er cl ose a n d a p pr o priate cli nical a n d/ or la b orat or y m o nit ori n g o nce t he 
I n v esti gat or will ha ve c o nsi dere d acc or di n g t o his/ her best me dical j u d g me nt t hat t he occ urre nce 
of t he c o ncer ne d e ve nt w as u nli kel y t o be relate d t o t he I M P. 
It is i n t he i nterest of t h e patie nt t o m o nit or bl o o d gl uc ose d uri n g t he te m p orar y disc o nti n uati o n 
peri o d, t heref ore re g ular deter mi nati o n of S M B G is t o be  perf or me d a n d d oc u me nte d. 
F or all te m p or ar y treat me nt disc o nti n uati o ns, d urati o n s h o ul d be rec o r d e d b y t he I n vesti gat or i n 
t he a p pr o priat e pa ges of t he e- C R F w h e n c o nsi dere d as c o nfir m e d. 
Te m p orar y tr eat me nt dis c o nti n uati o n deci de d b y t he I n vesti gat or c orres p o n ds t o m ore t ha n 1 d ose 
n ot a d mi nistere d t o t he patie nt. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 7 8 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 7 8 
Use of a n y differ e nt a nti- h y per gl yce mic me di cati o n d uri n g t he ti me of t e m p orar y treat me nt 
disc o nti n uati o n (ie, i ns uli n d uri n g a h os pitalizati o n) is rec or d e d as c o nc o mita nt me dicati o n wit h 
t he na me a n d d oses rec or de d i n t he e- C R F. 
1 0. 3. 2 P er m a n e nt tr e at m e nt di s c o nti n u ati o n wit h i n v e sti g ati o n al m e di ci n al pr o d u ct( s) 
Per ma ne nt treat me nt disc o nti n uati o n is a n y tr eat me nt disc o nti n uati o n ass ociate d wit h t he 
defi niti ve decisi o n fr o m t he I n vesti gat or or t h e patie nt n ot t o re-e x p ose t he patie nt t o t he I M P at 
a n y ti me. 
1 0. 3. 3 Li st of crit eri a f or p er m a n e nt tr e at m e nt di s c o nti n u ati o n 
T he patie nts ma y wit h dra w fr o m treat me nt wit h t h e I M P at a n y ti me f or a n y reas o n or t his ma y be 
t he I n v esti gat or’s decisi o n. Patie nts s h o ul d disc uss st o p pi n g st u d y me di cati o n wit h t he site bef ore 
d oi n g s o i n or der t hat q uesti o ns ca n be a d dre sse d, gl yce mic t hera p y a dj uste d, a n d a f oll o w- u p 
assess me nt arr a n ge d. All eff ort s s h o ul d be ma d e t o d oc u me nt t he reas o ns f or treat me nt 
disc o nti n uati o n a n d t his s h o ul d be d oc u me nte d i n t he e- C R F. 
T he f oll o wi n g reas o ns lea d t o per ma ne nt disc o nti n uati o n: 
•  At t he patie nt’s o w n re q u est (ie, w it h dra w al of c o nse nt f or treat me nt) 
•  If, i n t he I n vesti gat or's o pi ni o n, c o nti n uati o n wit h t he a d mi nistrati o n of t he st u d y treat me nt 
w o ul d be detri me ntal t o t he patie nt's well- bei n g 
•  I nter-c urre nt c o n diti o n t hat re q uires p er ma n e nt disc o nti n uati o n of t he st u d y treat me nt as 
l o n g as t he a b n or malit y p ersists a n d if t he cas u al relati o ns hi p of t he c o ncer ne d e ve nt a n d 
t he I M P is p ossi ble (acc or di n g t o t he I nv esti gat or’s best me dical j u d g m e nt) 
•  Pre g n a nc y (i n fe male p atie nts) 
•  S pecific re q u est of t he S p o ns or. 
A n y a b n or mal la b or at or y val ue w ill be i m me diatel y rec hec ke d f or c o nfir mati o n bef ore ma ki n g a 
decisi o n of per ma n e nt disc o nti n uati o n of  t he I M P f or t he c o n cer n e d patie nt. 
F or patie nts w h o pre mat urel y dis c o nti n ue t he I M P, t he assess me nts pla n ne d at E O T visit 
(Secti o n  1 0. 1. 3. 2 ) will be perf or me d at t he Pre mat ure E O T Visit, sc he d ule d prefera bl y pri or t o 
treat me nt disc o nti n uati o n or as s o o n as p ossi ble aft er ti me of disc o nti n uati o n (t he latest at t he ne xt 
o n-site visit). Reas o n f or I M P disc o nti n uati o n will be clearl y s p ecifie d. T his Pre mat ure E O T 
assess me nt ma y occ ur at a re g ularl y s c he d ul e d visit or at a n u nsc he d ule d visit. 
Patie nts partici pati n g i n t he A B P M s u bst u d y will n ot be re q uire d t o disc o nti n ue t he s u bst u d y i n 
t he e ve nt t hat t he y per ma ne ntl y disc o nti n ue treat ment i n t he mai n st u d y. E v er y eff ort s h o ul d be 
ma de t o e ns ure t h at disc o nti n ue d patie nts c o m plete t he A B P M s u bst u d y, if t he y are willi n g a n d 
a ble t o d o s o. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 7 9 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 8 0 
All st u d y wit h dra w als s h o ul d be rec or de d b y t he I n vesti gat or i n t he a p pr o priate scree ns of t he 
e- C R F a n d i n t he patie nt’s me dical rec or ds w he n c o nsi dere d as c o nfir me d. I n t he me dical rec or d, 
at least t he date of t he wit h dra wal  a n d t he reas o n s h o ul d be d oc u me nte d. 
F or patie nts w h o fail t o r et ur n t o t he site, u nle ss t he patie nt wit h dra ws c o nse nt f or f oll o w- u p, t he 
I n v esti gat or s h o ul d ma ke t he best eff ort t o reco ntact t he patie nt (e g, c o ntact patie nt’s fa mil y or 
pri vate p h ysicia n, r e vie w a vaila ble r e gistries or healt h care d ata bas es), a n d t o deter mi ne his/ her 
healt h stat us, i ncl u di n g at least his/ her vital stat us. Atte m pts t o c o ntact s uc h patie nts ( 3 p h o ne call 
atte m pts f oll o we d b y a certifie d letter) m ust be d o c u me nte d i n t he patie nt’s rec or ds (e g, ti mes a n d 
dates of atte m pte d tele p h o ne  c o ntact, recei pt f or s e n di n g a re gistere d letter). 
Patie nts w h o ha ve wit h dr a w n fr o m t he st u d y ca n n ot be rera n d o mize d (treat e d) i n t he st u d y. T h eir 
i ncl usi o n a n d treat me nt n u m bers m ust n ot be re use d.  
1 0. 4  
O B LI G A TI O N O F T H E I N V E S TI G A T O R R E G A R DI N G S A F E T Y R E P O R TI N G 
1 0. 4. 1 D efi niti o n s of a d v er s e e v e nt s  
1 0. 4. 1. 1 A d v er s e e v e nt 
A n a d verse e v e nt  ( A E) is a n y u nt o w ar d me dical occ urre nce i n a patie nt or cli nical i n vesti gati o n 
patie nt a d mi nistere d a p h ar mace u tical pr o d uct a n d w hic h d oes n ot necessaril y ha v e t o ha ve a 
ca usal relati o ns hi p wit h t his treat me nt. 
1 0. 4. 1. 2 S eri o u s a d v er s e e v e nt 
A seri o us a d verse e v e nt ( S A E) is a n y u nt o war d me dical occ urre n ce t hat at a n y d ose: 
•  Res ults i n deat h, or 
•  Is life-t hreate ni n g, or 
N ote : T he ter m “life-t hreate ni n g” i n t he defi niti o n of “seri o us” refers t o a n e ve nt i n w hic h t he 
patie nt was at ris k of d eat h at t he ti me of t he e ve nt; it d oes n ot refer t o a n e ve nt w hic h 
h y p ot heticall y mi g ht ha v e ca use d d eat h if it were m ore se vere. 
•  Re q uires i n patie nt h os pitalizati o n or pr ol o n gati o n of  e xisti n g h os pitalizati o n, or 
•  Res ults i n persiste nt or si g nifica nt disa bilit y/i n ca p acit y, or 
•  Is a c o n ge nital a n o mal y/ birt h defect 
•  Is a me dicall y i m p orta nt e ve nt 
Me dical a n d sci e ntific j u d g me nt  s h o ul d be e x ercise d i n deci di n g w het her e x pe dite d re p orti n g 
is a p pr o priate i n ot her sit uati o ns, s uc h as i m p orta nt me dical e ve nts t hat ma y n ot be 
i m me diatel y life-t hreat e ni n g or res ult i n deat h or h os pitalizati o n b ut ma y je o par dize t he 
patie nt or ma y re q uir e m e dical or s ur gical i n ter ve nti o n (ie, s pecific meas ures or c orrecti ve 
treat me nt) t o pre v e nt o ne of t he ot her o utc o mes liste d i n t he defi niti o n a b o ve. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 8 1 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 8 1 
N ote : T he f oll o wi n g list of me dicall y i m p orta nt e ve nts is i nte n de d t o ser ve as a g ui deli ne f or 
deter mi ni n g w hi c h c o n diti o n has t o  be c o nsi dere d as a me dically i m p orta nt e ve nt. T he list is 
n ot i nte n de d t o be e x ha usti ve: 
•  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 p as m  
- 
Bl o o d d ys crasias (ie, a gra n ul oc yt osis, a pl astic a ne mia, b o ne marr o w a plasi a, 
m yel o d ys plasia, p a nc yt o pe nia, etc),  
- 
C o n v ulsi o ns (seiz ures, e pile ps y, e pile ptic fit, a bse nce, etc). 
•  De vel o p me nt of dr u g d e pe n de nce or dr u g a b use 
•  A L T > 3 × U L N + t otal bilir u bi n > 2 × U L N or as y m pt o matic A L T i ncreas e > 1 0 × U L N 
•  S uici de atte m pt or a n y e v e nt s u g gesti ve of s uici dalit y 
•  S y nc o pe, l oss of c o nsci o us ness (e x ce pt if  d oc u me nte d as a c o ns e q ue nce of bl o o d 
sa m pli n g) 
•  B ull o us c uta ne o us er u pti o ns  
•  Ca ncers dia g n os e d d uri n g t he st u d y or a g gra v ate d d uri n g t he st u d y 
•  C hr o nic ne ur o de ge ner ati ve diseases ( n e wl y dia g n ose d) or a g gra vat e d d uri n g t he st u d y  
1 0. 4. 1. 3 A d v er s e e v e nt of s p e ci al i nt er e st 
A n A E SI is a n A E (seri o us or n o n-seri o us) of s cie ntific a n d me dical c o n cer n s pecific t o t he 
S p o ns or’s pr o d uct or pr o gr a m, f or w hi c h o n g oi n g m o nit ori n g a n d ra pi d c o m m u nicati o n b y t he 
I n v esti gat or t o t he S p o ns or ma y b e a p pr o priate. S uc h e ve nts ma y re q uire f urt her i n vesti gati o n i n 
or der t o c h aracterize a n d u n dersta n d t he m. A E SI s ma y b e a d de d or re m o v e d d uri n g a st u d y b y 
pr ot oc ol a me n d me nt. 
T he A E SI f or t his st u d y are: 
•  Pre g n a nc y of a fe m ale patie nt e ntere d i n a st u d y as well as pre g n a nc y occ urri n g i n a 
fe male part ner of a male patie nt e ntere d i n a st u d y wit h I M P/ NI M P: 
- 
Pre g n a nc y occ urri n g i n a fe male patie nt i ncl u d e d i n t he cli nical trial or i n a fe male 
part ner of a male p atie nt e ntere d i n t he cli nical trial. It will be q ualifie d as a n S A E o nl y 
if it f ulfills o ne of t he seri o us ness criteria (s ee Secti o n  1 0. 4. 1. 2 ), 
- 
I n t he e ve nt of pre g na n c y i n a fe male p atie nt, I M P s h o ul d be disc o nti n ue d,  
- 
F oll o w- u p of t he pre g na n c y i n a fe mal e patie nt or i n a fe male p art ner of a m ale patie nt 
is ma n dat or y u ntil t he o utc o me has bee n d eter mi n e d. 
•  S y m pt o matic o v er d ose wit h I M P/ NI M P: 
- 
A s y m pt o matic o ver d ose (acci d e ntal or i nte nti o nal) wit h t he I M P/ NI M P is a n e ve nt 
s us pecte d b y t he I n v esti gat or or s p o nta ne o usl y n otifie d b y t he p atie nt a n d res ulti n g i n 
cli nical s y m pt o ms a n d/ or si g ns acc o m pa nie d b y a d mi nistrati o n of m ore t ha n t wice t he 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 8 2 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 8 2 
i nte n de d dail y d os e wit hi n a 2 4- h o ur peri o d. It will be rec or de d i n t he e- C R F as a n 
A E SI wit h i m me diate n otificati o n “ S y m pt o matic O V E R D O S E (acci de ntal or 
i nte nti o nal)” i n all cases a n d will be q ualifie d as a n S A E o nl y if it f ulfills t he S A E 
criteria. 
( Please n ote t hat a n As y m pt o matic o verd ose wit h t he I M P/ NI M P, acci de nt al or 
i nte nti o nal, defi ne d a d mi nistrati o n of m ore t ha n t wice t he i nte n de d d ail y d ose wit hi n a 
2 4- h o ur peri o d, wit h o ut cli nical s y m pt o ms a n d/ or si g ns, eit her s us p ecte d b y t he 
I n v esti gat or or s p o nta ne o usl y n otifie d b y t he patie nt, n ot base d o n acc o u nt a bilit y 
assess me nt. It will be rec or de d as a n A E “ As y m pt o matic O V E R D O S E, acci de ntal or 
i nte nti o nal.”) 
•  A L T i n crease > 3 X U L N (ref er t o rel ate d fl o w c hart, A p pe n di x F ). 
1 0. 4. 1. 4 E v e nt s of s p e ci al i nt er e st 
A n E O SI is a seri o us or n o n-seri o us A E of s cie ntific a n d me dical c o ncer n s pecific t o t he 
S p o ns or’s pr o d uct or pr o gr a m, f or w hi c h o n g oi n g m o nit ori n g ma y be a p pr o priate. S uc h e ve nts 
ma y r e q uire f urt her i n v esti gati o n i n or der t o c haracterize a n d u n dersta n d t he m. T hese e v e nts 
s h o ul d be re p orte d o n t he s pecific e- C R F pa ge ( w h ere a p plica ble) a n d will o nl y q ualif y f or 
e x pe dite d re p orti n g w he n seri o us (f ulfilli n g S A E criteria). 
T he E O SI f or t his st u d y are: 
•  Maj or a d vers e car di o vas c ular e v e nts ( M A C E [car di o vasc ular deat h, MI, or str o ke]) a n d 
ot her s pecific C V e ve nts (e g, heart fail ure lea di n g t o h os pitalizati o n) 
•  Se vere h y p o gl yce mia (see Secti o n  1 0. 6. 1 ) 
•  Ge nital m yc otic i nfecti o ns (t o i ncl u de v ul v o va gi nal ca n di dias is i n fe males a n d ca n di dal 
bala nitis i n males) 
•  Uri nar y tract i nfe cti o ns 
•  Cli nicall y rele v a nt v ol u me de pleti o n a n d e v e nts rel ate d/ p ossi bl y rel ate d t o v ol u me 
de pleti o n 
•  Diarr he a 
•  Pa ncreatitis 
•  B o ne fract ures 
•  Ve n o us t hr o m b otic e ve nts t o i ncl u de dee p ve n o us t hr o m b osis a n d t hr o m b oe m b olis m (t o 
i ncl u de p ul m o nar y e m b olis m) 
•  Dia betic ket oaci d osis 
•  Re nal e ve nts t o i ncl u de 5 0 % decli ne i n e G F R, e n d sta ge ki d n e y disease, re n al deat h 
•  Mali g na n cies of s pecial i nterest ( breast, bla d der, re nal cell, Le y di g cell, pa ncreatic, 
pr ostate, a n d t h yr oi d c arci n o ma) 
•  A d verse e ve nt lea di n g t o a n a m p utati o n 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 8 3 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 8 3 
1 0. 4. 2 G e n er al g ui d eli n e s f or r e p orti n g a d v er s e e v e nt s 
•  All A Es, re gar dl ess of seri o us ness or rela ti o ns hi p t o I M P/ NI M P, s pa n ni n g fr o m t he 
si g nat ure of t he I C F u ntil t he e n d of t he st u d y as d efi ne d b y t he pr ot o c ol f or t hat patie nt, 
are t o be rec or de d o n t he c orres p o n di n g p a ge(s) or scree n(s) of t he e- C R F. 
•  W he ne ver p ossi ble, dia g n osis or si n gle s y n dr o me s h o ul d be re p orte d i nstea d of s y m pt o ms. 
T he I n vesti gat or s h o ul d s pecif y t he dat e of o ns et, i nte nsit y, acti o n ta k e n wit h res pect t o 
I M P, c orrecti ve treat me nt/t hera p y gi v e n, a d diti o nal i n vesti gati o ns perf or m e d, o utc o me, 
a n d his/ her o pi ni o n as t o w het her t here is a reas o n a ble p ossi bilit y t h at t he A E was ca use d 
b y t he I M P or b y t h e st u d y pr o ce d ure(s).  
•  I n t his st u d y, t he use of c o nc o mita nt me dicati o ns i ncl u di n g a nti dia b etic me dicati o ns ma y 
ma ke it diffic ult t o assess t he ca usal relati o ns hi p, partic ularl y f or h y p o gl yce mia. Gl o bal 
Safet y Officer wit h i n p ut fr o m ot her a p pr o pr iate st u d y tea m me m bers will d eter mi ne t he 
ca usal r elati o ns hi p w he n it is n ot clearl y pr o vi d e d b y t he I n vesti gat or. 
•  T he I n vesti gat or s h o ul d t a ke a p pr o priate meas ur es t o f oll o w all A Es u ntil cli nical rec o v er y 
is c o m plete a n d la b orat or y res ults ha ve ret ur ne d t o n or mal, or u ntil pr o gressi o n has bee n 
sta bilize d, or u ntil deat h, i n or der t o e ns ure t he safet y of t h e patie nts. T his ma y i m pl y t hat 
o bser vati o ns will c o nti n ue be y o n d t he last pla n ne d visit per pr ot oc ol , a n d t hat a d diti o nal 
i n vesti gati o ns ma y be r e q ueste d b y t he m o nit ori n g tea m u p t o as n otice d b y t he S p o ns or. 
•  W he n treat me nt is pre mat urel y disc o nti n ue d, t h e p atie nt’s o bser vati o ns will c o nti n ue u ntil 
t he e n d of t he st u d y as defi ne d b y t h e pr ot oc ol f or t hat patie nt. 
•  La b orat or y, vital si g ns or E C G a b n or malities are t o be rec or de d as A Es if t he y are 
me dicall y rele v a nt base d o n t he I n ves ti gat or’s me dical j u d ge me nt, e g,:  
- 
S y m pt o matic a n d/ or  
- 
Re q uiri n g eit her c orrecti ve trea t me nt or c o ns ultati o n, a n d/ or  
- 
Lea di n g t o I M P disc o nti n uati o n or m o dificati o n of d osi n g, a n d/ or  
- 
F ulfilli n g a s eri o us ness criteri o n, a n d/ or  
- 
Defi ne d as a n A E SI or E O SI. 
1 0. 4. 3 I n str u cti o n s f or r e p orti n g s eri o u s a d v er s e e v e nt s 
I n t he cas e of occ urr e nce of a n S A E, t he I n v esti gat or or a n y desi g nees m ust i m me diatel y: 
•  E N T E R ( wit hi n 2 4 h o urs) t he i nf or mati o n rel ate d t o t he S A E i n t he a p pr o priate scree ns of 
t he e- C R F; t he s yste m will a ut o maticall y se n d t he n otificati o n t o t he M o nit ori n g tea m a n d 
P har mac o vi gila nce after a p pr o val of t he I n vesti gat or wit hi n t he e- C R F: 
•  S E N D ( pref er a bl y b y fa x or e- mail) a p h ot o c o p y of all e x a mi nati o ns carrie d o ut a n d t he 
dates o n w hic h t hese e x a mi nati o ns  were perf or me d, t o t he re pres e ntati ve of t he m o nit ori n g 
tea m w h ose na me, fa x n u m ber, a n d e mail a d dress a p pear o n t h e cli n ical trial pr ot oc ol. 
Care s h o ul d be ta ke n t o e ns ure  t hat t he patie nt's i d e ntit y is pr otect e d a n d t h e patie nt's 
i de ntifiers i n t he cli nical trial are pr o p erl y me nti o ne d o n a n y c o p y of a s o urce d oc u m e nt 
pr o vi de d t o t he S p o ns or. F or la b orat or y res ults, i ncl u de t he la b orat or y n or mal ra n ges. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 8 4 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 8 4 
•  All f urt her data u p d ates s h o ul d be rec or de d  i n t he e- C R F as a p pr o priate, a n d f urt her 
d oc u me ntati o n as well as a d diti o nal i nf or mati o n (f or la b orat or y d ata, c o n c o mita nt 
me dicati o ns, patie nt stat us, etc)  s h o ul d be se nt ( b y fa x or e-mail) t o t he m o nit ori n g tea m 
wit hi n 2 4 h o urs of k n o wle d ge of t he S A E. I n a d diti o n, e ver y eff ort s h o ul d b e ma de t o 
f urt her d oc u m e nt a n y S A E t hat is fatal or life t hreate ni n g wit hi n a w ee k ( 7 d a ys) of t he 
i nitial n otificati o n. 
•  A bac k- u p pla n ( usi n g a pa per C R F pr o cess) is a v aila ble a n d s h o ul d be use d w he n t he 
e- C R F s yste m d oes n ot w or k. 
A n y S A E br o u g ht t o t he atte nti o n of t he I n vesti gat or at a n y ti me after t he e n d of t he st u d y f or t he 
patie nt a n d c o nsi der e d b y hi m/ her  t o be ca use d b y t he I M P wit h a reas o n a ble p ossi bilit y, s h o ul d 
be re p ort e d t o t he m o nit ori n g tea m. 
1 0. 4. 4 G ui d eli n e s f or r e p orti n g a d v er s e e v e nt s of s p e ci al i nt er e st  
F or A E SIs, t he S p o ns or m ust be i nf or me d i m me diatel y (i e, wit hi n 2 4 h o urs), as per S A E 
n otificati o n g ui deli nes descri be d i n Secti o n  1 0. 4. 3 , e ve n if n ot f ulfilli n g a seri o us ness criteri o n, 
usi n g t he c orres p o n di n g pa ges of t he e- C R F (t o b e se nt) or scree ns i n t he e- C R F. 
1 0. 4. 5 G ui d eli n e s f or r e p orti n g e v e nt s of s p e ci al i nt er e st 
If a n E O SI f ulfills t he criteria of a n S A E, re p orti n g s h o ul d be p erf or m e d acc or di n g t o t he 
i nstr ucti o ns f or re p orti n g of S A Es (see Secti o n  1 0. 4. 3 ). Ot her wise, re p orti n g s h o ul d f oll o w t he 
i nstr ucti o ns f or a n A E (s ee Secti o n  1 0. 4. 2 ). 
1 0. 4. 6 G ui d eli n e s f or m a n a g e m e nt of s p e cifi c l a b or at or y a b n or m aliti e s 
Decisi o n trees f or t he ma na ge me nt of certai n la b orat or y a b n or m alities b y S a n ofi are pr o vi de d i n 
A p pe n di x F . 
T he f oll o wi n g l a b orat or y a b n or malities s h o ul d be m o nit ore d, d oc u m e nte d, a n d ma na ge d 
acc or di n g t o t he relate d fl o w c hart i n pr ot oc ol a p p e n dices.  
•  Ne utr o pe nia 
•  T hr o m b oc yt o p e nia 
•  I n crease i n A L T 
•  Ac ute re n al i ns ufficie n c y 
•  S us pici o n of r ha b d o m y ol ysis 
1 0. 5  
O B LI G A TI O N S O F T H E S P O N S O R 
D uri n g t h e c o urs e of t he st u d y, t he S p o ns or will re p ort i n a n e x pe dite d ma n ner: 
•  All S A Es t hat are b ot h u ne x pecte d a n d at leas t reas o na bl y relat e d t o t he I M P (s us pecte d 
u ne x pecte d seri o us a d verse reacti o n [ S U S A R]), t o t he re g ulat or y a ut h orities, i n de pe n de nt 
et hics c o m mittees (I E Cs)/i nstit uti o nal re vie w b oar ds (I R Bs) as a p pr o pri ate a n d t o t he 
I n v esti gat ors. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 8 5 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 8 5 
•  All S A Es t hat are e x pect e d a n d at least reas o n a bl y relate d t o t he I M Ps t o t he re g ulat or y 
a ut h orities, acc or di n g t o l ocal re g ulati o ns. 
•  T he f oll o wi n g A E SIs t o t h ose re g ulat or y a ut h orities w h o re q uire s uc h re p orti n g: 
- 
Pre g n a nc y 
- 
S y m pt o matic o v er d ose 
- 
A L T i n cre ase > 3 X U L N 
A d verse e ve nts t hat ar e c o nsi dere d e x pecte d will be s pecifie d b y t h e refere nce safet y i nf or mati o n 
pr o vi de d i n t he c urr e nt I B.  
If re q uir e d, u n bli n di n g of S U S A Rs will be t he res p o nsi bilit y of t he S p o ns or. 
T he S p o ns or will re p ort all safet y  o bs er vati o ns ma de d uri n g t he co n d uct of t he trial i n t he C S R. 
1 0. 6  S A F E T Y I N S T R U C TI O N S 
1 0. 6. 1 H y p o gl y c e mi a 
D uri n g t h e st u d y, p atie nts are i nstr ucte d t o d o c u me nt a n y h y p o gl yce mic e pis o des i n t heir st u d y 
diar y. T he h y p o gl yce mia will be re p orte d i n t he s p ecific e- C R F pa ge wit h o nset date a n d ti me, 
s y m pt o ms a n d/ or si g ns, t he S M B G val ue if a vaila ble, a n d t he treat me nt. If t he e ve nt f ulfills S A E 
criteria, h y p o gl yce mia will als o be re p orte d as a n S A E. 
H y p o gl yce mia is cate g orize d acc or di n g t o t he A D A w or k gr o u p o n h y p o gl yce mia classificati o n 
(1 3 , 1 4 ) a n d s u m marize d i n Fi g ure 1 . 
I n a d diti o n t o t he t hres h ol d of ≤3. 9 m m ol/ L ( ≤7 0 m g/ d L), h y p o gl yce mia e pis o des wit h a plas ma 
gl uc ose of < 3. 0 m m ol/ L ( < 5 4 m g/ d L) will be a nal yz e d se paratel y. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 8 6 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 8 6 
Fi g ur e 1 - H y p o gl y c e mi a cl a s sifi c ati o n i n St u d y E F C 1 4 8 3 4 
 
Se vere h y p o gl yce mi a 
Se vere h y p o gl yce mia is a n e ve nt r e q uiri n g assista nce of a n ot h er pers o n t o acti vel y a d mi nister 
car b o h y dr ate, gl uca g o n, i ntra ve n o us gl uc ose or ot her res us citati ve acti o ns. T hese e pis o des ma y b e 
ass ociate d wit h s uffici e nt ne ur o gl yc o pe nia t o i n d u ce seiz ure, u nc o ns ci o us ness or c o ma. 
Self- m o nit ore d plas ma gl uc ose val ues ma y n ot b e a vaila ble, b ut ne ur ol o gical  rec o v er y attri b uta ble 
t o t he rest orati o n of plas ma gl ucos e t o n or mal is c o nsi dere d s ufficie nt e vi de nce t hat t he e ve nt w as 
i n d uce d b y a l o w plas ma gl uc ose c o nce ntrati o n. 
N ote : “re q uiri n g assista nce of a n ot h er pers o n” mea ns t hat t he patie nt c o ul d n ot hel p hi mself or 
herself t o treat t he h y p o gl yce mia. Assisti n g a p atie nt o ut of ki n d ness, w he n assista nce is n ot 
re q uire d, s h o ul d n ot be c o nsi dere d a “re q uires assista nce” i nci de nt. 
A n y h y p o gl yce mic e v e nt w hic h lea ds t o u nc o ns ci o us ness, c o ma, or seiz ure s h o ul d als o be 
re p orte d as a n S A E.  
D oc u me nte d s y m pt o m atic h y p o gl yce mi a 
D oc u me nte d s y m pt o matic h y p o gl yce mia is a n e v e nt d uri n g w hic h t y pical s y m pt o ms of 
h y p o gl yce mia acc o m pa nie d b y a meas ure d plas m a gl u c ose c o n ce ntrati o n of ≤3. 9 m m ol/ L 
(≤7 0 m g/ d L).  
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 8 7 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 8 7 
Cli nical s y m pt o ms t hat are c o nsi der e d t o res ult fr o m a h y p o gl yce mic e pis o de are e g, i ncrease d 
s weati n g, ner v o us n ess, ast he nia/ wea k ness, tre m or, dizzi ness, i ncrease d a p p etite, pal pitati o ns, 
hea dac he, slee p dis or d er, c o nf usi o n, seiz ures, u nc o nsci o us ness, or c o ma. 
As y m pt o m atic h y p o gl yce mi a 
As y m pt o matic h y p o gl yce mia is a n e ve nt n ot acc o m pa nie d b y t y pical s y m pt o ms of h y p o gl yce mia 
b ut wit h a meas ure d plas ma gl uc os e c o nce ntrati o n ≤3. 9 m m ol/ L ( ≤7 0 m g/ d L).   
N ote:  l o w plas ma gl u c os e val ues wit h o ut s y m pt o ms or si g ns s h o ul d n ot be re p orte d m ore t ha n 
o nce wit hi n 3 0 mi n utes.  Re peate d l o w gl uc os e va l ues wit hi n a s h ort peri o d c o ul d be d ue t o 
malf u ncti o n of t he de vice, err or te sti n g or f oll o wi n g u p a l o w gl u c ose rea di n g. T he I n vesti gat or 
s h o ul d tr y n ot t o d oc u me nt false l o w S M B G val u es or re d u n da nt l o w gl uc ose val ues as 
as y m pt o matic h y p o gl yce mic e ve nt. F urt h er cl arifi cati o n wit h t he patie nts is nee de d. 
Pr o b a ble s y m pt o m atic h y p o gl yce mi a 
Pr o ba ble s y m pt o matic h y p o gl yce mia is a n e ve nt d u ri n g w hi c h s y m pt o ms of h y p o gl yce mia are n ot 
acc o m pa ni e d b y a plas m a gl u c ose deter mi nati o n, ( b ut t hat was pres u ma bl y ca use d b y a pl as ma 
gl uc ose c o nce ntrati o n ≤3. 9 m m ol/ L [ ≤7 0 m g/ d L]), ie, s y m pt o ms treate d wit h oral car b o h y drate 
wit h o ut  a test of plas ma gl uc ose.  
Rel ati ve h y p o gl yce mi a 
Relati ve h y p o gl yce mia, r ece ntl y ter me d “ pse u d o- h y p o gl yce mia” (1 5 ) is a n e ve nt d uri n g w hic h t he 
patie nt re p orts t y pical s y m pt o ms of h y p o gl yce mia, a n d i nter prets t he s y m pt o ms as i n dicati ve of 
h y p o gl yc e mia, b ut wit h a meas ure d plas ma gl u c os e c o nce ntrati o n > 3. 9 m m ol/ L ( > 7 0 m g/ d L). 
1 0. 7  
A D V E R S E E V E N T S M O NI T O RI N G 
All e ve nts will be ma na ge d a n d re p orte d i n c o m plia nce wit h all a p plica bl e re g ulati o ns, a n d 
i ncl u de d i n t he fi nal C S R. 
 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 8 8 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 8 8 
1 1  
S T A TI S TI C A L C O N SI D E R A TI O N S 
1 1. 1  
D E T E R MI N A TI O N O F S A M P L E SI Z E 
T he sa m ple size/ p o wer calc ula ti o ns are b ase d o n t he pri mar y varia ble, c h a n ge fr o m Baseli ne t o 
Wee k 2 6 i n H b A 1c. Ass u mi n g a c o m m o n sta n dar d de viati o n ( S D) of 1. 2 %  a n d usi n g a 2-si de d 
test at a 0. 0 5 α -le v el, 2 5 0 patie nts per ar m will ha v e at least 9 9 % p o w er t o d etect a treat me nt 
differe n ce of 0. 6 % i n mea n H b A 1c c ha n ge fr o m Baseli ne t o Wee k 2 6 b et wee n s ota glifl ozi n 
4 0 0 m g a n d place b o. 
T he sa m ple siz e/ p o wer c alc ulati o ns f or A B P M  s u bst u d y are bas e d o n t he pri mar y varia bl e, 
c ha n ge fr o m Baseli ne t o Wee k 1 2 i n a ver a ge 2 4- h o ur S B P i n patie nts wit h mea n 
S B P ≥1 3 0 m m H g at Scr ee ni n g. Ass u mi n g a c o m m o n S D of 1 5 m m H g a n d usi n g a 2-si d e d test at 
a 0. 0 5 α -le v el, 1 0 0 patie nts per ar m will pr o vi de 9 0 % p o wer t o det ect a treat me nt differe n ce of 
7 m m H g i n a vera ge 2 4- h o ur S B P c ha n ge fr o m Baseli ne t o Wee k 1 2 bet wee n s ota glifl ozi n 4 0 0 m g 
a n d place b o. 
1 1. 2  
DI S P O SI TI O N O F P A TI E N T S 
T he t otal n u m ber of patie nts f or eac h of t he f oll o wi n g cate g ories will be prese nte d i n t he C S R: 
•  Scree ne d p atie nts: patie nts w h o ha ve si g n e d t he I C F 
•  R u n-i n patie nts 
•  Ra n d o mize d patie nts: patie nts wit h a treat me nt  kit n u m ber all ocate d a n d rec or de d i n I R T 
data base, a n d re gar dless of w het her t h e treat me nt kit was use d or n ot 
•  T he safet y p o p ulati o n (i e, ra n d o mize d a n d treat e d patie nts) 
•  T he i nte nt-t o-treat (I T T) p o p ulati o n (as defi ne d i n Secti o n  1 1. 3. 1. 1  a n d a nal yz e d as 
ra n d o mize d) 
•  T he ra n d o mizati o n strata ( H b A 1c at Scree ni n g [≤8. 0 %, > 8. 0 %], a n d S B P 
[ < 1 3 0, ≥1 3 0 m m H g]). T he discre p a nc y bet w ee n t h e strata assi g ne d b y I R T a n d t he 
i nf or mati o n re p orte d o n e- C R F will be liste d f or all ra n d o mize d patie nts 
•  Patie nts w h o ha ve c o m pl ete d t he 2 6- wee k mai n treat me nt peri o d 
•  Patie nts w h o disc o nti n ue d t he I M P d uri n g t he 2 6- wee k mai n treat me nt peri o d, a n d t he 
reas o ns f or treat me nt dis c o nti n uati o n 
•  Patie nts w h o ha ve c o m pl ete d t he e ntire treat me nt peri o d 
•  Patie nts w h o disc o nti n ue d t he I M P d uri n g t he e ntire treat me nt peri o d, a n d t he reas o ns f or 
treat me nt disc o nti n uati o n 
•  Patie nts w h o ha ve c o m pl ete d t he st u d y 
•  Patie nts w h o disc o nti n ue d t he st u d y, a n d t he reas o ns f or st u d y disc o nti n uati o n 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 8 9 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 8 9 
F or all cate g ories of patie nts e x ce pt scree ne d, p erce nta ges will be calc ulate d usi n g t he n u m ber of 
ra n d o mize d patie nts as de n o mi nat or f or eac h treat me nt gr o u p. 
A list of patie nts pre mat urel y dis c o nti n ue d fr o m t h e treat me nt, al o n g wit h reas o ns f or 
disc o nti n uati o n, will be pr o vi de d. Si milarl y, a list of patie nts pre mat urel y disc o nti n ue d fr o m t he 
st u d y, al o n g wit h reas o ns f or disc o nti n uati o n, w ill be pr o vi de d. 
Patie nts treate d b ut n ot ra n d o miz e d, patie nts ra n d o mize d b ut n ot treate d a n d patie nts ra n d o mize d 
b ut n ot treate d as ra n d o mize d will be i de ntifie d a n d descri be d i n se p arat e listi n gs. T he safet y 
e x perie nce of p atie nts treate d a n d n ot ra n d o mize d will be re p orte d se p aratel y, a n d t h ese patie nts 
will n ot be i n t he safet y p o p ulati o n. 
F or a n y p atie nt ra n d o mize d m ore t ha n o nce, o nl y t h e data ass o ciate d wit h t he first ra n d o mizati o n 
will be use d i n a n y a nal ysis p o p ulati o n. T he sa fet y e x perie n ce ass o ciate d wit h a n y lat er 
ra n d o mizati o n will be assesse d se paratel y. 
1 1. 3  
A N A L Y SI S P O P U L A TI O N S 
1 1. 3. 1 Effi c a c y p o p ul ati o n s 
Efficac y a nal ys es will be base d o n t he treat me nt  gr o u p all ocate d b y t he I R T acc or di n g t o t he 
ra n d o mizati o n sc he d ule at ra n d o mizati o n visit (as ra n d o mize d), irres pecti ve of t he treat me nt 
act uall y recei ve d. 
1 1. 3. 1. 1 I nt e nt-t o-tr e at p o p ul ati o n 
Efficac y a nal ys es will be base d o n t he I T T p o p ul ati o n, defi ne d as a ll ra n d o mize d patie nts, 
irres pecti ve of c o m plia nce wit h t he st u d y pr ot o c ol a n d pr oce d ures. Patie nts will be a nal yze d f or 
efficac y a n al ys es acc or di n g t o t he treat me nt gr o u p t o w hic h t he y are ra n d o mize d. 
1 1. 3. 2 S af et y p o p ul ati o n 
Safet y a nal yses will be base d o n t he safet y p o p ulati o n, defi ne d as all ra n d o mize d patie nts w h o 
recei v e at least 1 d ose of d o u ble- bli n d I M P (re gardless of t he a m o u nt of treat me nt a d mi nistere d). 
Patie nts will be a nal yze d f or saf et y a nal yses  acc or di n g t o t he treat me nt act u all y recei v e d. 
I n a d diti o n: 
•  N o nra n d o mize d b ut treat e d patie nts will n ot be part of t he safet y p o p ul ati o n, b ut t heir 
safet y data will be prese nte d se paratel y 
•  Ra n d o mize d patie nts f or w h o m it is u nclear w het h er t he y t o o k t he st u d y me dicati o n will 
be i ncl u de d i n t he saf et y p o p ulati o n as ra n d o mize d 
•  W he n a patie nt is e x p ose d t o b ot h s ota glifl ozi n a n d place b o, t he p atie nt will be a nal yz e d i n 
t he s ota glifl ozi n gr o u p  
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 9 0 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 9 0 
•  Ra n d o mize d patie nts will be e x cl u de d fr o m t he safet y p o p ulati o n o nl y if t here is 
d oc u me nte d e vi de n ce (i e, all st u d y dates rec o r de d as n o me dicati o n ta ke n) t hat patie nts 
ha ve n ot ta ke n t he st u d y me dicati o n 
1 1. 4  
S T A TI S TI C A L M E T H O D S 
C o nti n u o us data will be s u m ma rize d b y treat me nt gr o u p usi n g t he n u m ber of o bser vati o ns 
a vaila ble, mea n, S D, mi ni m u m, me dia n, a n d ma xi m u m. Cate g orical data will be s u m marize d b y 
treat me nt gr o u p usi n g c o u nt a n d perce nta ge. 
I n ge neral, descri pti ve statistics of q ua ntitati ve efficac y a n d s afet y p ara met ers (res ult a n d c ha n ge 
fr o m Bas eli ne) b y sc h e d ule d visits will be pr o vi de d o n o bser ve d cas es ( O C), ie, i ncl usi o n of o nl y 
patie nts ha vi n g n o n- missi n g asse ss me nts at a s pecific visit. 
T he baseli ne v al ue is defi ne d ge ner all y as t he last a vaila ble val ue b ef ore t h e first d ose of 
d o u ble- bli n d I M P or t he l ast a vaila ble val u e pri or t o ra n d o mizati o n f or patie nts w h o were 
ra n d o mize d b ut ne ver e x p ose d t o I M P. 
F or ser u m creati ni ne a n d e G F R, t he Bas eli ne val ue is  defi ne d as t he a v era ge of all val ues bef ore 
t he first d ose of d o u ble- bli n d I M P f or t h ose ra n d omize d a n d e x p ose d or bef ore ra n d o mizati o n f or 
t h ose w h o wer e ra n d o mi ze d b ut ne ver e x p ose d t o I M P. 
A nal ysis of d e m o gra p hics a n d baseli ne c h aracteristics, pri or a n d c o nc o mita nt me dicati o ns will be 
pr o vi de d i n detail i n t he statis tical a nal ysis pla n ( S A P). 
1 1. 4. 1 E xt e nt of st u d y tr e at m e nt e x p o s ur e a n d c o m pli a n c e 
T he e xte nt of st u d y treat me nt e x p os ure a n d c o m plia nce will be assess e d a n d s u m marize d b y 
act ual treat me nt recei ve d i n t he safet y p o p ulati o n. 
1 1. 4. 1. 1 E xt e nt of i n v e sti g ati o n al m e di ci n al pr o d u ct e x p o s ur e 
T he e xte nt of st u d y treat me nt e x p os ure will be assesse d b y t he d urati o n of treat me nt e x p os ure 
d uri n g t he st u d y.  
T he d urati o n of treat me nt e x p os ure will be t he t otal n u m ber of da ys of a d mi nistrati o n of t he 
d o u ble- bli n d I M P, r e gar dless of u n pla n ne d i nter m itte nt disc o nti n uati o ns. T he d urati o n of I M P 
e x p os ure will be calc ulat e d as: 
( Date of t h e last d o u ble- bli n d I M P ta ke n – D ate of t he first d o u ble- bli n d I M P ta ke n) + 1. 
T he n u m ber ( %) of p atie nts ra n d o mize d a n d e x p os e d t o d o u ble- bli n d I M P will be prese nte d b y 
s pecific ti me peri o ds f or eac h tr eat me nt gr o u p. T h e ti me peri o ds of i nterest will be defi ne d i n t he 
S A P. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 9 1 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 9 1 
Descri pti ve statistics of d urati o n of treat me nt  e x p os ure ( n u m ber, m ea n, S D, mi ni m u m, me dia n, 
a n d ma xi m u m) a n d c u m ulati ve e x p os ure i n patie nt year will als o be prese nte d b y treat me nt gr o u p 
i n t he safet y p o p ulati o n. 
1 1. 4. 1. 2 C o m pli a n c e  
A gi ve n a d mi nistrati o n will be c o nsi dere d n o nc o m plia nt if t he pa tie nt di d n ot ta ke t he pla n ne d 
d ose of treat me nt as re q uire d b y t h e pr ot oc ol. N o i m p utati o n will be ma de f or patie nts wit h 
missi n g or i nc o m plete data.  
Treat me nt c o m plia nce, a b o ve- p la n ne d a n d u n der- pla n ne d d osi n g p erce nta ges will be s u m marize d 
descri pti vel y ( N, mea n, S D, me di a n, mi n, a n d ma x). T he perce nta ge  of p atie nts wit h c o m plia nce 
< 8 0 % will be s u m marize d. I n a d diti o n, t he n u m ber a n d perce nta ge of patie nts wit h at least 
1 a b o ve- pla n n e d d osi n g a d mi nistra ti o n will be gi ve n, as well as t he n u m b er a n d perce nta ge of 
patie nts wit h 0, > 0 t o 2 0 % , a n d > 2 0 % u n d er- pl a n ne d d osi n g a d mi nistrati o ns. 
1 1. 4. 2 A n al y s e s of effi c a c y e n d p oi nt s 
Efficac y a nal ys es will be perf or me d o n t he I T T p o p ulati o n. 
Statistical testi n g will be perf or me d f or pri mar y  e n d p oi nt a n d sec o n dar y e n d p oi nts at Wee k 2 6 ( or 
Wee k 1 2 f or S B P). All efficac y v aria bles after Wee k 2 6 will o nl y be s u m m arize d b y d escri pti ve 
statistics wit h o ut f or mal statistical testi n g. 
1 1. 4. 2. 1 A n al y si s of pri m ar y effi c a c y e n d p oi nt 
T he statistical test will be t w o-si de d tests at a n o mi nal 5 % si g nifica nce le vel. 
A nal ysis of t h e pri mar y efficac y e n d p oi nt (c h a n ge fr o m Bas eli ne t o Wee k 2 6 i n H b A 1c; see 
Secti o n  9. 1. 1 ) will be perf or me d o n t he I T T p o p ul atio n, usi n g H b A 1 c meas ure me nts o btai ne d 
fr o m visits d uri n g t he st u d y, i ncl u di n g t h ose o btaine d after I M P disc o nti n uati o n or i ntr o d ucti o n of 
resc ue t h era p y. 
T he pri mar y efficac y e n d p oi nt of c ha n ge i n H b A 1 c fr o m baseli ne t o Wee k 2 6 will be a nal yze d 
wit h missi n g val ues i m p ute d b y c o ntr ol- base d m ulti ple i m p utati o n met h o d u n der t he missi n g n ot 
at ra n d o m fr a me w or k.  
•  F or place b o patie nts, missi n g data will be i m p ute d base d o n t he place b o gr o u p data. 
•  F or patie nts i n t he s ota glifl ozi n gr o u p, missi n g da t a will be i m p ute d as if t he patie nts were 
o n place b o t hr o u g h o ut t h e st u d y. 
Eac h of t he c o m plete dat asets will be a nal yz e d b y a n A nal ysis of C o varia n ce ( A N C O V A) m o del 
wit h treat me nt gr o u ps (s ota glifl ozi n, pl ace b o), ra n d o mizati o n strat u m of H b A 1c ( ≤8. 0 %, > 8. 0 %), 
ra n d o mizati o n strat u m of S B P ( < 1 3 0, ≥1 3 0 m m H g), a n d c o u ntr y as fi x e d effects, a n d b aseli ne 
H b A 1c val ue as a c o vari ate. Res ults fr o m eac h c o m plete dataset will be c o m bi ne d t o pr o vi de t he 
a dj uste d mea n c h a n ge i n H b A 1c fr o m Bas eli ne t o  Wee k 2 6 f or eac h treat me nt gr o u p, as well as 
t he bet wee n- gr o u p diff er e nce ( c o m pari n g s ota glifl ozi n vs place b o) a n d t he 9 5 % c o nfi de n ce 
i nter val ( CI) f or t he diff ere nce.  
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 9 2 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 9 2 
S u m mar y statistics (f or s cree ni n g v al ue, bas eli n e val ue, o bser v e d val ues, a n d o bser ve d c h a n ges 
fr o m Bas eli ne) at s c he d ule d visits will be pr o vi de d f or eac h treat me nt gr o u p. T he s u m mar y will 
i ncl u de t he n u m ber of o bser vati o ns, mea n, S D, sta n dar d err or ( S E), mi ni m u m, me dia n, a n d 
ma xi m u m. Gra p hical prese ntati o ns will als o be use d t o e x a mi ne tre n ds o ver ti me usi n g mea n 
val ues ( ± S E) a n d mea n c ha n ges fr o m Bas eli ne ( ± S E) at eac h of t he sc h e d ule d visits ( usi n g O C). 
Assess me nt of tre at me nt eff ect b y s u b gr o u p  
Descri pti ve a n al ys es will be perf or me d o n t he pri mar y e n d p oi nt t o s u m marize t he treat me nt 
effects acr oss s u b gr o u ps defi ne d b y t he f o ll o wi n g Baseli ne or Scree ni n g fact ors: 
•  Race 
•  Et h nicit y ( His pa nic, N ot His pa nic) 
•  A ge gr o u p ( < 5 0 years, ≥5 0 t o < 6 5 years, ≥6 5 years) 
•  Ge n der 
•  Baseli ne B MI le v el ( < 3 0, ≥3 0 k g/ m²) 
•  Baseli ne H b A 1c ( ≤8. 0 %, > 8. 0 %)  
•  Baseli ne H b A 1c ( ≤8. 5 %, > 8. 5 %)  
•  Baseli ne S B P ( < 1 3 0 m m H g, ≥1 3 0 m m H g)  
•  C o u ntr y 
T he treat me nt effects acr oss t he s u b gr o u ps d efi ne d f or eac h of t hes e fact ors will be esti mate d f or 
t he c ha n ge fr o m Baseli ne t o Wee k 2 6 i n H b A 1c i n t he I T T p o p ulati o n, a n d usi n g a si milar 
a p pr oac h t o t he a nal ysis f or t he pri mar y effica c y e n d p oi nt. T he a dj uste d esti mates of treat me nt 
mea n differe nces (s ota glifl ozi n vers us place b o) wit h S E a n d 9 5 % CIs will b e pr o vi de d as 
a p pr o priate acr oss t he s u b gr o u ps. 
I n t he cas e t hat t he s u b gr o u p fact or is i de ntical or si milar t o a ra n d o mizati o n strata fact or (e g, 
baseli ne H b A 1 c cate g or y), o nl y t he s u b gr o u p fact or  will be i ncl u de d i n t he m o del i n or der t o 
a v oi d t he iss ue of c olli nearit y i n t he a nal ysis. 
1 1. 4. 2. 2 A n al y s e s of s e c o n d ar y effi c a c y e n d p oi nt s 
T he sec o n d ar y e n d p oi nts (see Secti o n  9. 1. 2 ) will be a nal yz e d usi n g a si milar a p pr o ac h t o t he 
pri mar y efficac y e n d p oi nt wit h missi n g val ues  i m p ute d b y c o ntr ol- base d m ulti ple i m p utati o n 
met h o d u n der t he missi n g n ot at r a n d o m fra m e w or k.  
•  F or place b o patie nts, missi n g data will be i m p ute d base d o n t he place b o gr o u p data. 
•  F or patie nts i n t he s ota glifl ozi n gr o u p, missi n g da t a will be i m p ute d as if t he patie nts were 
o n place b o gr o u p t hr o u g h o ut t he st u d y. 
F or eac h of t h e c o nti n u o us sec o n dar y e n d p oi nts, eac h  of t h e c o m plete d atasets will be a nal yze d b y 
a n A N C O V A m o del wit h treat me nt gr o u ps (s ota g lifl ozi n, place b o), ra n d omizati o n strat u m of 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 9 3 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 9 3 
H b A 1c ( ≤8. 0 %, > 8. 0 %), ra n d o miz ati o n st rat u m of S B P ( < 1 3 0 m m H g, ≥1 3 0 m m H g), a n d c o u ntr y 
as fi x e d effects, a n d baseli ne sec o n dar y e n d p oi nt val ue as a c o vari ate. Res ults fr o m eac h c o m plet e 
dataset will be c o m bi ne d t o pr o vi de t he a dj uste d m ea n c h a n ge fr o m Bas eli ne t o Wee k 2 6 ( or 
Wee k 1 2 f or S B P) f or eac h treat me nt gr o u p, as w ell as t he bet wee n- gr o u p differe n ce (c o m pari n g 
s ota glifl ozi n vs place b o) a n d t he 9 5 % CI f or t he differe nce.  
T he cate g orical sec o n dar y efficac y varia bles of H b A 1c < 6. 5 %, < 7 % at Wee k 2 6 will be a nal yz e d 
usi n g a C oc hra n- M a ntel- Hae nszel met h o d stra tifie d b y ra n d o mizati o n strat u m of H b A 1c (≤8. 0 %, 
> 8. 0 %), a n d ra n d o miz ati o n st rat u m of S B P ( < 1 3 0 m m H g, ≥1 3 0 m m H g). T he pr o p orti o n i n eac h 
treat me nt gr o u p will be pr o vi de d, as well as t he differe nce of pr o p orti o ns b et wee n s ota glifl ozi n 
a n d place b o wit h ass ociate d 2-si de d 9 5 % CI . F or H b A 1c res p o n ders at Wee k 2 6 ( < 6. 5 %, 
< 7 % res p ecti vel y), all val ues at Wee k 2 6 will be use d t o deter mi ne w h et her a patie nt is a 
res p o n der or n ot, e ve n if t he y are meas ure d after I M P disc o nti n uati o n or resc ue me dicati o n use. 
Patie nts w h o ha ve n o H b A 1c meas ur e me nt at Wee k 2 6 will be treate d as n o n-res p o n ders. 
F or all sec o n dar y e n d p oi nts, s u m ma r y statistics at sc he d ule d visits will be pr o vi de d f or eac h 
treat me nt gr o u p. T he s u m mar y will i ncl u de t he n um ber of o bser v ati o ns, mea n, S D, S E, mi ni m u m, 
me dia n, a n d ma xi m u m. Gra p hical prese ntati o ns will als o be use d t o e x a mi ne tre n ds o ver ti me 
usi n g mea n v al ues ( ± S E) a n d mea n c h a n ges fr o m baseli ne ( ± S E) at eac h of t he sc he d ule d visits 
( usi n g O C). 
1 1. 4. 2. 3 A n al y s e s of ot h er effi c a c y e n d p oi nt s 
T he a nal ysis of ot her e n d p oi nts (see Secti o n  9. 1. 3 ) will be descri pti ve wit h n o f or mal testi n g. 
S u m mar y statistics at sc h e d ule d visits usi n g O C will be pr o vi de d b y eac h treat me nt gr o u p. 
Gra p hical prese ntati o ns will als o be use d t o ill ustrate tre n ds o v er ti me. 
1 1. 4. 2. 4 A n al y si s of a m b ul at or y bl o o d pr e s s ur e m o nit ori n g s u b st u d y e n d p oi nt s 
A B P M s u bst u d y e n d p oi nts will be a nal yze d usi n g a si milar a p pr oac h as t he pri mar y efficac y 
e n d p oi nt wit h missi n g val ues i m p ute d b y c o ntr ol- base d m ulti ple i m p utati o n met h o d u n der t he 
missi n g n ot at ra n d o m fra me w or k. E ac h of t h e c o m plete dataset will be a n al yze d usi n g 
A N C O V A m o del i ncl u di n g f act ors f or treat me nt (s ota glifl ozi n, place b o), ra n d o mizati o n strat u m 
of H b A 1c ( ≤8. 0 %, > 8. 0 %) as fi x e d effects, a n d t he baseli ne val u e of t he s pecific de p e n de nt 
varia ble as a c o v ariate.  
1 1. 4. 2. 5 M ulti pli cit y c o n si d er ati o n s 
T o c o ntr ol t he fa mil y- wise t y pe I err or, a fi x e d se q ue nce testi n g pr o ce d ure will be a p plie d. O nce 
t he mai n st u d y pri mar y v aria ble (c ha n ge fr o m Bas eli ne t o Wee k 2 6 i n H b A 1c) is statisticall y 
si g nifica nt at α = 0. 0 5 ( 2-si de d), a hierarc hi cal testi n g pr o ce d ure will be perf or me d t o test t he 
f oll o wi n g mai n st u d y sec o n dar y efficac y vari a bles a n d A B P M s u bst u d y pri mar y e n d p oi nt b y t h e 
f oll o wi n g pri oritize d or d er. T he testi n g will sto p as s o o n as a n e n d p oi nt is f o u n d t o be n ot 
statisticall y si g nifica nt at α = 0. 0 5 ( 2-si d e d). 
•  C ha n ge fr o m Baseli ne t o Wee k 2 6 i n 2- h o ur P P G f oll o wi n g a n M M 
•  C ha n ge fr o m Baseli ne t o Wee k 2 6 i n F P G 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 9 4 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 9 4 
•  C ha n ge fr o m Baseli ne t o Wee k 2 6 i n b o d y w ei g ht 
•  C ha n ge fr o m Baseli ne t o Wee k 1 2 i n S B P f or patie nts wit h baseli ne S B P ≥1 3 0 m m H g 
•  C ha n ge fr o m Baseli ne t o Wee k 1 2 i n S B P f or all patie nts 
•  C ha n ge fr o m Baseli ne t o Wee k 1 2 i n a vera ge 2 4- h o ur S B P i n patie nts fr o m A B P M 
s u bst u d y (t he pri mar y e n d p oi nt of t he A B P M s u bst u d y) 
•  Pr o p orti o n of patie nts wit h H b A 1c < 7. 0 % at Wee k 2 6. 
N o m ulti plicit y a dj ust me nt will be  ma de o n ot her sec o n dar y efficac y v aria bles t ha n me nti o ne d 
a b o ve. 
1 1. 4. 3 A n al y s e s of s af et y d at a 
Safet y e n d p oi nts are pres e nte d i n Secti o n  9. 2. T he s u m mar y of safet y res ults will be prese nte d b y 
treat me nt gr o u p. T he s af et y d ata will be s u m mari ze d f or t he 2 6- we e k C ore Treat me nt Peri o d a n d 
t he e ntire treat me nt peri o d se parat el y, u nl ess s pecifie d ot her wise. All safet y a nal ys es will be 
perf or me d o n t h e Safet y p o p ulati o n as defi ne d i n Secti o n  1 1. 3. 2  usi n g t he f oll o wi n g c o m m o n 
r ules: 
T he f oll o wi n g d efi niti o ns will be a p plie d t o la b orat or y para met ers a n d vital si g ns: 
•  T he p ote ntiall y cli nicall y si g nifica nt a b n or ma lit y ( P C S A) val ues f or cli nical la b orat or y 
tests a n d vital si g ns ar e d efi ned as a b n or mal val ues c o nsi dere d  me dicall y i m p orta nt b y t he 
S p o ns or’s Gl o bal P har mac o vi gila nce a n d E pi de mi ol o g y de part me nt a n d i n effect at t he 
ti me of t he fi nal S A P a p pr o val. P C S A criteria f or para meters n ot cite d i n t he pr ot oc ol as 
safet y para meters will n ot be a nal yz e d, 
•  P C S A criteria will deter mi ne w hic h patie nts ha d at least 1 P C S A d uri n g t h e o n-treat me nt 
peri o d, ta ki n g i nt o acc o u nt all e val uati o ns  perf or me d d uri n g t he o n-treat me nt peri o d, 
i ncl u di n g u nsc he d ul e d or re peat e d e val u ati o ns. T he n u m ber of all s uc h patie nts will be t he 
n u merat or f or t he o n-tr eat me nt P C S A perce nta ge. 
T he “ o bser v ati o n peri o ds ” defi ne d i n Secti o n  9. 2. 1  are a p plica ble f or classificati o n of A Es, 
deter mi nati o n of o n-tr eat me nt P C S A val ues a n d t he last o n-treat me nt v al ue f or t he la b orat or y, 
vital si g n a n d E C G para meters. 
1 1. 4. 3. 1  A n al y si s of a d v er s e e v e nt s 
Pre-t re at me nt A Es  are A Es t hat de vel o pe d or w orse ne d or b eca m e seri o us d uri n g t he 
pre-treat me nt peri o d. 
Tre at me nt-e mer g e nt A Es  are A Es t hat de v el o pe d or w orse n e d (acc or di n g t o t he I n v esti gat or’s 
o pi ni o n) or beca m e seri o us d uri n g t he o n-treat me nt peri o d. 
P ost-tre at me nt A Es  ar e A Es t hat de vel o pe d or w orse ne d or b eca m e seri o us d uri n g t he 
p ost-treat me nt peri o d. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 9 5 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 9 5 
T he pri mar y f o c us of A E re p orti n g i n t he C S R will be o n T E A Es. Pre- a n d p ost-treat me nt A Es 
will be descri be d se p aratel y. 
All a d verse e ve nts 
A d verse e ve nt i nci de n ce ta bles will prese nt b y s yste m or ga n class ( S O C) (s orte d b y 
i nter nati o nall y a gree d or der), hi g h-le v el gr o u p ter m ( H L G T), hi g h le vel ter m ( H L T) a n d preferre d 
ter m ( P T) s orte d i n al p ha betical or der f or eac h treat me nt gr o u p, t h e n u m ber ( n) a n d p erce nta ge 
( %) of p atie nts e x perie nci n g a n A E. M ulti ple occ urrences of t he sa m e e ve nt i n t he sa me patie nt 
will be c o u nte d o nl y o n ce i n t he ta bles w it hi n a treat me nt p hase. T h e de n o mi nat or f or 
c o m p utati o n of perce nta ges is t he safe t y p o p ulati o n wit hi n eac h treat me nt gr o u p.  
S u m maries of all T E A Es i n eac h  treat me nt gr o u p will i ncl u de: 
•  T he o ver vie w of A Es, s u m marizi n g n u m ber ( %) of patie nts wit h a n y 
- 
T E A E 
- 
Seri o us T E A E 
- 
T E A E lea di n g t o deat h 
- 
T E A E lea di n g t o per m a n e nt treat me nt disc o nti n uati o n 
•  T he n u m ber ( n) a n d perce nta ge ( %) of p atie nt s wit h at least o ne T E A E b y pri mar y S O C, 
H L G T, H L T a n d P T 
•  S u m mar y of T E A Es b y ma xi mal se verit y (se v ere, m o derate, mil d), pres e nte d b y pri mar y 
S O C a n d P T 
•  S u m mar y of T E A Es p ossi bl y relat e d t o I M P, prese nte d b y pri mar y S O C, H L G T, H L T a n d 
P T. 
A detaile d listi n g of T E A E s u m maries will be pr o vi de d i n t he S A P. 
De at h a n d seri o us a d verse e ve nts 
Deat h a n d treat me nt-e m er ge nt S A Es will be s u m marize d a n d prese nt e d as n u m ber a n d perce nt of 
patie nts i n eac h tr eat me nt gr o u p. 
T he f oll o wi n g d eat hs s u m maries will be ge nerate d: 
•  N u m ber ( %) of patie nts w h o die d b y st u d y p e ri o d ( o n-st u d y, o n-treat me nt, p ost-st u d y) 
s u m marize d o n t he safet y p o p ulati o n b y treat me nt recei ve d. 
•  Deat h i n n o nra n d o mize d patie nts or ra n d o mize d a n d n ot treate d patie nts 
•  T E A E lea di n g t o deat h ( deat h as a n o utc o m e o n t he A E e- C R F p a ge as re p orte d b y t h e 
I n v esti gat or) b y pri mar y S O C, H L G T, H L T a n d P T s h o wi n g n u m ber ( %) of patie nts 
s orte d b y i nter nati o nall y a gree d or der of S O C a n d al p ha betic or d er of H L G T, H L T, a n d 
P T. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 9 6 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 9 6 
A d verse e v e nts le a di n g t o per m a ne nt tre at me nt disc o nti n u ati o n 
Treat me nt-e mer ge nt A Es lea di n g t o p er ma ne nt treat me nt disc o nti n uati o n will be s u m marize d a n d 
prese nte d as n u m ber a n d perce nt of  patie nts i n eac h treat me nt gr o u p. 
1 1. 4. 3. 2 A n al y s e s of h y p o gl y c e mi a 
T he n u m ber ( %) of p atie nts a n d rate  i n patie nt years ( 2 t y pes: t he n u m ber of patie nts wit h e ve nts 
or t he t otal n u m ber of e v e nts pe r 1 0 0 patie nt- year) of all, se vere, a n d d o c u me nte d s y m pt o matic 
h y p o gl yce mia will be s u m marize d b y treat me nt gr o u p res pecti vel y. T heir patter n of occ urre nce 
o ver ti me will als o be ass esse d, as a p pr o priate. 
1 1. 4. 3. 3 A n al y s e s of a d v er s e e v e nt s of s p e ci al i nt er e st 
Pre g n a nc y a n d o ver d os e will be i ncl u de d i n o verall A E s u m maries if a n y are re p ort e d. A L T 
i ncreas e > 3 × U L N is i ncl u de d i n la b orat or y P C S A s u m mar y if a n y. 
1 1. 4. 3. 4 A n al y s e s of e v e nt s of s p e ci al i nt er e st 
T he n u m ber ( %) of p atie nts wit h eac h E O SI e v e nt will be s u m marize d b y treat me nt gr o u p. All 
e ve nts re p ort e d b y t he I n vesti gat ors o n t he A E f or ms f or s pecial i nterests will be liste d al o n g wit h 
t he a dj u dicati o n o utc o me (if a p plica ble). 
1 1. 4. 3. 5 A n al y s e s of l a b or at or y v ari a bl e s 
T he n u m ber a n d p erce nta ge of patie nts wit h P C S A  or b y t he pre- defi ne d cat e g ories (if n o P C S A 
criteri o n is defi ne d) at a n y e v al uati o n d uri n g t he o n-treat me nt peri o d will be s u m marize d f or eac h 
cli nical la b orat or y test wit hi n eac h treat me nt gr o u p. T he s u m maries will i ncl u de patie nts i n t he 
safet y p o p ulati o n w h o ha ve at least o ne la b orat or y test perf or me d d uri n g t h e o n-treat me nt peri o d 
a n d, w he n r e q uire d b y t h e defi niti o n of t he a b n or malit y, wit h a n a v aila ble baseli ne val ue a n d 
a vaila ble la b or at or y n or mal ra n ges. 
Descri pti ve statistics will be use d t o s u m marize t he la b orat or y res ults a n d t he c ha n ges fr o m 
baseli ne b y visit a n d f or t he last o n-treat me nt v al ue wit hi n eac h treat me nt gr o u p. S hift ta bles a n d 
ot her ta b ular a n d gra p hical met h o ds  ma y b e use d t o prese nt t he res ults f or la b orat or y tests of 
i nterest. Listi n gs will be pr o vi de d wit h fla gs i n dicati n g t he o ut of la b orat or y ra n ge val u es as w ell 
as t he P C S A val ues. 
T he li ver f u ncti o n tests, na mel y A L T, A S T, al kali ne p h os p hatase, a n d t ota l bilir u bi n, are use d t o 
assess p ossi ble dr u g-i n d u ce d li ver t o xicit y. T he pr o p orti o n of patie nts wit h P C S A val ues at a n y 
p ost baseli ne visit b y baseli ne stat us will be di s pla ye d b y treat me nt gr o u p f or eac h p ara met er. 
1 1. 4. 3. 6 A n al y s e s of vit al si g n v ari a bl e s 
T he n u m ber a n d p erce nta ge of patie nts wit h P C S A at a n y e val u ati o n d uri n g t he o n-treat me nt 
peri o d will be s u m marize d f or eac h vital si g n  p ara meter wit hi n eac h treat m e nt gr o u p. T he 
s u m maries will i ncl u de patie nts i n t he safet y p o p ulati o n w h o ha ve at least o ne para m eter t o be 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 9 7 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 9 7 
a nal yze d d uri n g t h e o n-tr eat me nt peri o d. Descri pt i ve statistics will be use d t o s u m marize t he 
res ults a n d t he c ha n ges fr o m baseli ne b y visit a n d f or t he last o n-treat me nt val ue wit hi n eac h 
treat me nt gr o u p. Ta b ul ar a n d gra p hical met h o ds ma y b e use d t o prese nt t he res ults f or para meters 
of i nterest. Listi n gs will be pr o vi de d wit h fla gs i n dicati n g t he P C S A val ues. 
1 1. 4. 3. 7 A n al y s e s of 1 2 l e a d E C G st at u s 
A s hift ta ble will be pr o vi de d t o prese nt t he E C G o n-treat me nt stat us acc or di n g t o t he baseli ne 
stat us wit hi n eac h treat m e nt gr o u p. 
1 1. 4. 4 A n al y s e s of p h ar m a c o ki n eti c v ari a bl e s 
T he P K e n d p oi nt is prese nte d i n Secti o n  9. 3. 1 . I n di vi d ual plas ma c o nce ntrati o ns of s ota glifl ozi n 
a n d of its 3- O- gl uc ur o ni de at n o mi nal sa m pli n g ti mes will be liste d.  
C o nce ntrati o n data will b e s u m marize d b y visit a n d, if a p pr o priate, wit hi n visit b y n o mi nal 
sa m pli n g ti mes ( pre- d ose, 2 h o ur 3 0 mi n ute p ost-d ose), usi n g d escri pti ve st atistics b y N, 
ge o m etric mea n, c oeffici e nt of  variati o n, me dia n, mi ni m u m a n d ma xi m u m at eac h visit/ n o mi nal 
sa m pli n g ti me p oi nt f or s ota glifl ozi n-treate d p atie nts. 
1 1. 5  I N T E RI M A N A L Y SI S 
N o f or mal i nteri m a nal ysis f or efficac y is pla n n e d f or t his st u d y. T he st u d y will n ot be ter mi nate d 
earl y f or e x celle nt effi cac y. 
A n i n de pe n de nt D M C will m o nit or a n d assess t he safet y of patie nts fr o m t his trial t hr o u g h 
peri o dic re vi e w of t he acc u m ulate d safet y d ata  pr o vi de d b y a n i n de pe n d e nt statistical gr o u p. 
Relate d details ar e pr o vi de d i n se par ate d oc u me nts ( D M C c harter a n d D M C S A P). 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 9 8 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 9 9 
T he cli nical trial (st u d y n u m ber, cli nical trial pr ot o c ol title a n d versi o n n u m ber), t he d o c u me nts 
re vie we d (cli nical trial pr ot oc ol, I C F, I B wit h a n y a d de n da or l a beli n g d oc u me nts (s u m mar y of 
pr o d uct c haract eristics, pac ka ge i nsert), I n v esti gat or’s c urric ul u m vitae, etc) a n d t he date of t he 
re vie w s h o ul d be clearl y state d o n t he writte n (I R B/I E C) a p pr o val/fa v ora ble o pi ni o n. 
T he I M P will n ot be release d at t he st u d y site a n d t he I n v esti gat or will n ot start t he st u d y b ef ore 
t he writte n a n d date d a p pro val/fa v or a ble o pi ni o n is recei v e d b y t he I n vesti gat or a n d t he S p o ns or. 
D uri n g t h e cli nical trial, a n y a me n d me nt or m o dificati o n t o t he cli nical trial pr ot oc ol s h o ul d be 
s u b mitte d t o t he healt h a ut h orities (c o m pete nt re g ulat or y a ut h orit y), as re q uire d b y l o cal 
re g ulati o n, i n a d diti o n t o t he I R B/I E C, bef ore i m pl e me ntati o n, u nless t he c h a n ge is necessar y t o 
eli mi nate a n i m me diate h azar d t o t he patie nts, i n w hic h case t h e healt h a ut h orities (c o m pete nt 
re g ulat or y a ut h orit y) a n d t he I R B/I E C s h o ul d be i nf or me d as s o o n as p ossi ble. T he y s h o ul d als o 
be i nf or me d of a n y e ve nt li kel y t o affect t he s a fet y of patie nts or t he c o nti n ue d c o n d uct of t he 
cli nical trial, i n partic ular a n y c ha n ge i n safet y. All u p dates t o t he I B or la beli n g i nf or mati o n, will 
be se nt t o t he I R B/I E C a n d t o healt h a ut h orities (c o m pete nt re g ulat or y a ut h orit y), as re q uire d b y 
l ocal re g ulati o n. 
A pr o gress r e p ort is se nt t o t he I R B/I E C at least a n n uall y a n d a s u m mar y of t he cli nical trial’s 
o utc o me at t he e n d of t h e cli nical trial. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 0 0 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 0 0 
1 3  
S T U D Y M O NI T O RI N G 
1 3. 1  
R E S P O N SI BI LI TI E S O F T H E I N V E S TI G A T O R 
T he I n vesti gat or is r e q uir e d t o e ns ure c o m plia nce w it h all pr oce d ures re q uire d b y t he cli nical trial 
pr ot oc ol a n d wit h all st u d y pr o ce d ur es pr o vi de d b y t he S p o ns or (i ncl u di n g s ec urit y r ules). T h e 
I n v esti gat or a grees t o pr o vi de relia ble dat a a n d all i nf or mati o n re q ueste d b y t he cli nical trial 
pr ot oc ol ( wit h t he hel p of t he C R F, Discre p a nc y R es ol uti o n F or m [ D R F] or ot her a p pr o pri ate 
i nstr u me nt) i n a n acc urat e a n d le gi ble ma n n er acc or di n g t o t he i nstr ucti o ns pr o vi de d a n d t o e ns ure 
direct access t o s o urce d o c u me nts b y S p o ns or re prese ntati ves. 
If a n y cir c uit i ncl u des tra nsfer of d ata partic ul ar atte nti o n s h o ul d be pai d t o t he c o nfi de ntialit y of 
t he patie nt's d ata t o be tra nsferr e d. 
T he I n vesti gat or ma y a p p oi nt s uc h ot her i n di vi d uals as he/s he ma y dee m a p pr o priate as 
S u bi n vesti gat ors t o assist i n t he c o n d uct of t he cli nical trial i n acc o r da nce wit h t he cli nical trial 
pr ot oc ol. All S u bi n vesti gat or s s hall be a p p oi nte d a n d liste d i n a ti mel y m a n ner. T he 
S u bi n vesti gat ors will be s u per vise d b y a n d w or k  u n der t he res p o nsi bilit y of t he I n vesti gat or. T h e 
I n v esti gat or will pr o vi de t he m wit h a c o p y of t he cli nical trial pr otoc ol a n d all necessar y 
i nf or mati o n. 
1 3. 2  
R E S P O N SI BI LI TI E S O F T H E S P O N S O R O R S E R VI C E P R O VI D E R 
T he S p o ns or a n d/ or ser vi ce pr o vi der of t his cli nical tria l is res p o nsi ble t o re g ulat or y a ut h orities f or 
ta ki n g all r eas o na bl e ste ps t o e ns ure t he pr o p er c o n d uct of t he cli nical trial as re gar ds et hics, 
cli nical trial pr ot oc ol c o m plia nce, a n d i nte grit y a n d vali dit y of t he dat a rec or de d o n t he C R Fs. 
T h us, t he mai n d ut y of t h e m o nit ori n g tea m is t o h el p t he I n vesti gat or a n d t he S p o ns or mai ntai n a 
hi g h le vel of et hical, scie ntific, tec h nical a n d re g ul at or y q u alit y i n all as p ects of t he cli nical trial. 
At re g ular i nter v als d uri n g t he cli nical trial, t he site will be c o ntacte d, t hr o u g h m o nit ori n g visits, 
letters or tele p h o ne calls, b y a repr ese ntati ve of t he m o nit ori n g tea m t o re vie w st u d y pr o gress, 
I n v esti gat or a n d patie nt c o m plia nce wit h cli nical trial pr ot oc ol re q uireme nts a n d a n y e mer ge nt 
pr o ble ms. T hese m o nit ori n g visits will i ncl u de b ut n ot be li mite d t o re vie w of t he f oll o wi n g 
as pects: patie nt i nf or me d c o nse nt, patie nt recr uit me nt a n d f oll o w-u p, S A E d oc u me ntati o n a n d 
re p orti n g, A E SI d oc u me ntati o n a n d re p orti n g, A E a n d E O SI d oc u me ntati o n, I M P all ocati o n, 
patie nt c o m plia nce wit h t he I M P re gi me n, I M P acc o u nta bilit y, c o n c o mita nt t hera p y use a n d 
q ualit y of dat a. 
1 3. 3  S O U R C E D O C U M E N T R E Q UI R E M E N T S 
Acc or di n g t o t he I C H G C P, t he m o nit ori n g tea m m ust c hec k t he C R F e ntri es a gai nst t he s o urce 
d oc u me nts, e x ce pt f or t h e pre-i d e ntifie d s o urce data directl y rec or de d i n t h e C R F. T he I C F will 
i ncl u de a state me nt b y w hic h t he patie nt all o ws t he S p o ns or’s d ul y a ut h ori ze d pers o n nel, t he 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 0 1 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 0 1 
et hics c o m mittee (I R B/I E C), a n d t he re g ul at or y a u t h orities t o ha ve direct access t o ori gi nal 
me dical rec or ds w hic h s u p p ort t he data o n t he C R F s (e g, p atie nt's me dical file, a p p oi nt me nt 
b o o ks, ori gi nal la b or at or y r ec or ds, etc). T h ese pers o n nel, b o u n d b y pr ofessi o nal secrec y, m ust 
mai ntai n t he c o nfi de ntialit y of all pers o nal i de ntit y or p ers o nal me dical i nf or mati o n (acc or di n g t o 
c o nfi de ntialit y a n d pers o nal  data pr otecti o n r ules). 
1 3. 4  
U S E A N D C O M P L E TI O N O F C A S E R E P O R T F O R M S ( C R F S) A N D A D DI TI O N A L 
R E Q U E S T 
It is t he r es p o nsi bilit y of t he I n v esti gat or t o mai ntai n a de q uat e a n d acc urat e case re p ort f or ms 
( C R Fs) (acc or di n g t o t he tec h n ol o g y us e d) desi g ne d b y t he S p o ns or/ser vi ce pr o vi der t o rec or d 
(acc or di n g t o S p o ns or i nstr ucti o ns) all o bser vati o ns a n d ot her data p erti ne nt t o t he cli nical 
i n vesti gati o n i n a ti mel y ma n ner. All C R Fs s h o ul d be c o m plete d i n t heir e ntiret y i n a n eat, le gi ble 
ma n ner t o e ns ur e acc ur ate  i nter pret ati o n of data. 
S h o ul d a c orrecti o n be ma de, t he c orrecte d i nf or m ati o n will be e n tere d i n t he e- C R F o v er writi n g 
t he i nitial i nf or mati o n. A n a u dit trail all o ws i de ntif yi n g t he m o dificati o n.  
Data ar e a v aila ble wit hi n t he s yste m t o t he S p o ns or as s o o n as t he y are e ntere d i n t he e- C R F. 
T he c o m p uterize d ha n dli n g of t he data b y t he S p o ns or/ser vice pr o vi der ma y ge n erat e a d diti o nal 
re q uests ( D R F) t o w hic h t he I n v esti gat or is o bli ge d t o res p o n d b y c o nfir mi n g or m o dif yi n g t he 
data q uesti o ne d. T he re q uests wit h t heir re s p o nses will be ma na ge d t hr o u g h t he e- C R F. 
1 3. 5  
U S E O F C O M P U T E RI Z E D S Y S T E M S 
T he c o m plete list of c o m p uterize d s yste ms use d f or t he st u d y is pr o vi de d i n a se parate d oc u m e nt 
w hic h is mai ntai ne d i n t he S p o ns or/ser vi ce pr o vi der a n d I n v esti gat or st u d y files. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 0 2 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 0 2 
1 4  
A D DI TI O N A L R E Q UI R E M E N T S 
1 4. 1  
C U R RI C U L U M VI T A E 
A c urr e nt c o p y of t he c urric ul u m  vitae descri bi n g t he e x perie nce, q u alificati o n a n d trai ni n g of 
eac h I n v esti gat or a n d S u bi n vesti gat or will be si g n e d, date d a n d pr o vi de d t o t he S p o ns or/ser vice 
pr o vi der pri or t o t he b e gi n ni n g of t he cli nical trial. 
1 4. 2  
R E C O R D R E T E N TI O N I N S T U D Y SI T E S 
T he I n vesti gat or m ust mai ntai n  c o nfi de ntial all st u d y d oc u m e ntati o n, a n d t a ke meas ures t o 
pre ve nt acci de ntal or pre mat ure destr ucti o n of t h ese d oc u me nts. 
T he I n vesti gat or s h o ul d r etai n t he st u d y d o c u me nts at least 1 5 years after t he c o m pleti o n or 
disc o nti n uati o n of t he cli nical trial. 
H o we ver, a p plica ble re g ulat or y re q uire m e nts s h o ul d be ta ke n i nt o acc o u nt i n t he e ve nt t hat a 
l o n ger p eri o d is re q uir e d. 
T he I n vesti gat or m ust n otif y t he S p o ns or pri or t o destr o yi n g a n y st u d y ess e ntial d oc u me nts 
f oll o wi n g t he cli nical trial c o m pleti o n or disc o nti n uati o n. 
If t he I n vesti gat or's p ers o nal sit uati o n is s uc h t hat arc hi vi n g ca n n o l o n ger b e e ns ure d b y hi m/ her, 
t he I n v esti gat or s hall i nf or m t he S p o ns or a n d t he rele va nt rec or ds s h all be tra nsferre d t o a 
m ut uall y a gr ee d u p o n desi g nee. 
1 4. 3  
C O N FI D E N TI A LI T Y 
All i nf or mati o n discl ose d or pr o vi de d b y t he S p o ns or ( or a n y c o m pa n y/i nstit uti o n acti n g o n t heir 
be half), or pr o d uce d d uri n g t he cli nical trial, i ncl u di n g, b ut n ot li mite d t o, t he cli nical trial 
pr ot oc ol, pers o nal dat a i n  relati o n t o t he patie nts, t he C R Fs, t he I B a n d t he res ults o btai ne d d uri n g 
t he c o urse of t h e cli nical trial, is c o nfi de ntial, pri or t o t he p u blicati o n of res ults. T he I n v esti gat or 
a n d a n y pers o n u n d er his/ her a ut h orit y a gree t o u n de rta ke t o kee p c o nfi de ntial a n d n ot t o discl ose 
t he i nf or mati o n t o a n y t hir d part y wit h o ut t he pri or writte n a p pro val of t h e S p o ns or. 
H o we ver, t he s u b missi o n of t his cli nical trial pr ot oc ol a n d ot her necessar y d oc u me ntati o n t o t he 
et hics c o m mittee (I R B/I E C) is e x pressl y per mitte d, t he I R B/I E C me m bers ha vi n g t he s a me 
o bli gati o n of c o nfi de ntialit y. 
T he S u bi n vesti gat ors s hall be b o u n d b y t he sa m e o bli gati o n as t he I n v esti gat or. T he I n v esti gat or 
s hall i nf or m t he S u bi n vesti gat ors of t he c o nfi de ntial nat ure of t he cli nical trial. 
T he I n vesti gat or a n d t he S u bi n vesti gat ors s hall us e t he i nf or mati o n s olel y f or t he p ur p oses of t h e 
cli nical trial, t o t he e x cl usi o n of a n y us e f or t h eir o w n or f or a t hir d part y's acc o u nt. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 0 3 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 0 4 
1 4. 6  I N S U R A N C E C O M P E N S A TI O N 
T he S p o ns or certifies t h at it has ta ke n o ut a lia bilit y i ns ura n ce p olic y c o veri n g all cli nical tri als 
u n der its s p o ns ors hi p. T his i ns ura nce p olic y is i n  acc or da n ce wit h l ocal la ws a n d re q uire m e nts. 
T he i ns ura nce of t he S p o ns or d oes n ot relie ve t h e I n v esti gat or a n d t he c olla b orat ors fr o m a n y 
o bli gati o n t o mai ntai n t heir o w n lia bilit y i ns u ra n ce p olic y. A n i ns ura nce certificate will be 
pr o vi de d t o t he I E Cs/I R Bs or r e g ulat or y a ut h or iti es i n c o u ntries re q uiri n g t his d oc u me nt. 
1 4. 7  S P O N S O R A U DI T S A N D I N S P E C TI O N S B Y R E G U L A T O R Y A G E N CI E S 
F or t he p ur p os e of e ns uri n g c o m plia n ce wit h t he cli n ical trial pr ot oc ol, g o o d cli nical practice, a n d 
a p plica ble r e g ulat or y r e q uire me nts, t he I n vesti gat or s h o ul d per mit a u diti n g b y  or o n t h e be half of 
t he S p o ns or a n d i ns pecti o n b y r e g ulat or y a ut h orities. 
T he I n vesti gat or a grees t o all o w t he a u dit ors/i n s pect ors t o ha ve direct access t o his/ her st u d y 
rec or ds f or r e vie w, bei n g u n derst o o d t hat t hese pers o n nel is b o u n d b y pr ofessi o nal secrec y, a n d as 
s uc h will n ot discl ose a n y pers o nal i de ntit y or pers o nal me dical i nf or mati o n. 
T he I n vesti gat or will ma ke e ver y eff ort t o hel p wit h t he perf or ma n ce of t he a u dits a n d i ns pecti o ns, 
gi vi n g access t o all necessar y facilities, data, a n d d oc u me nts. 
As s o o n as t he I n vesti gat or is n otifie d of a pl a n ne d i ns pecti o n b y t he a ut h orities, he/s he will 
i nf or m t he S p o ns or a n d a ut h orize t he S p o nsor t o partici pate i n t his i ns pecti o n. 
T he c o nfi de ntialit y of t he data verifi e d a n d t he pr otecti o n of t he patie nts s h o ul d be res pecte d 
d uri n g t hes e i ns pecti o ns. 
A n y res ult a n d i nf or mati o n arisi n g fr o m t he i ns pecti o ns b y t he re g ulat or y a ut h orities will be 
i m me diatel y c o m m u nicat e d b y t h e I n vesti gat or t o t he S p o ns or. 
T he I n vesti gat or s hall ta k e a p pr o pri ate meas ures re q uire d b y t he S p o ns or t o ta ke c orrecti ve 
acti o ns f or all pr o ble ms f o u n d d ur i n g t he a u dit or i ns pecti o ns. 
1 4. 8  P R E M A T U R E DI S C O N TI N U A TI O N O F T H E S T U D Y O R P R E M A T U R E C L O S E- O U T O F 
A SI T E 
1 4. 8. 1 B y t h e S p o n s or  
T he S p o ns or has t he ri g ht t o ter mi nat e t he partici p ati o n of eit her a n i n di vi d ual site or t he st u d y at 
a n y ti me, f or a n y r eas o n, i ncl u di n g b ut n ot li mite d t o t he f oll o wi n g:  
•  T he i nf or mati o n o n t he pr o d uct lea ds t o d o u bt as t o t he be nefit/ris k rati o 
•  Patie nt e nr oll me nt is u nsatisfact or y 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 0 5 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 0 5 
•  T he I n vesti gat or h as recei ve d fr o m t he S p o ns or all I M P, mea ns, a n d i nf or m ati o n necessar y 
t o perf or m t he cli nical trial a n d has n ot i ncl u de d a n y patie nt after a reas o na ble peri o d of 
ti me m ut uall y a gree d u p o n 
•  N o nc o m plia nce of t h e I n vesti gat or or S u bi n ve sti gat or, dele gat e d staff wit h a n y pr o visi o n 
of t he cli nical trial pr ot oc ol, a n d breac h of t he a p plica ble la ws  a n d re g ulati o ns or breac h of 
t he I C H G C P 
•  T he t otal n u m ber of patie nts are i ncl u de d earlier t ha n e x pecte d. 
I n a n y cas e t he S p o ns or will n otif y t h e I n vesti gat or of its decisi o n b y writte n n otice. 
1 4. 8. 2 B y t h e I n v e sti g at or 
T he I n vesti gat or ma y t er mi nate his/ her partici pat i o n u p o n t hirt y ( 3 0) d a ys' pri or writte n n otice if 
t he st u d y site or t he I n vesti gat or f or a n y reas o n bec o mes u na ble t o perf or m or c o m plete t he 
cli nical trial.  
I n t he e ve nt of pre mat ur e disc o nti n uati o n of t he st u d y or pre mat ure cl ose- o ut of a site, f or a n y 
reas o n w h ats oe ver, t h e a p pr o priate I R B/I E C a n d re g ul at or y a ut h orities s h o ul d be i nf or me d 
acc or di n g t o a p plica ble r e g ul at or y re q uire me nts. 
1 4. 9  
C LI NI C A L T RI A L R E S U L T S 
T he S p o ns or will be res p o nsi ble f or pre p ari n g a C S R a n d t o pr o vi de a s u m mar y of st u d y res ults t o 
t he I n v esti gat or. 
1 4. 1 0  P U B LI C A TI O N S A N D C O M M U NI C A TI O N S 
T he I n vesti gat or u n d erta kes n ot t o ma ke a n y p u blica ti o n or release pertai ni n g t o t he st u d y a n d/ or 
res ults of t he st u d y pri or t o t he S p o ns or’s written c o nse nt, bei n g u n derst o o d t hat t he S p o ns or will 
n ot u nreas o na bl y wit h h ol d its a p pr o val. 
As t he st u d y is bei n g c o n d ucte d at m ulti ple site s, t he S p o ns or a grees t hat, c o nsiste nt wit h 
scie ntific sta n dar ds, a pri mar y prese nt ati o n or p u blicati o n of t he st u d y res ults base d o n gl o b al 
st u d y o utc o mes s hall be s o u g ht. H o w e ver, if n o m ultice nter p u blicati o n is s u b mitte d, u n der wa y, 
or pla n ne d wit hi n t wel ve ( 1 2) m o nt hs of t he c o m pl eti o n of t his st u d y at all sites, t he I n v esti gat or 
s hall ha ve t he ri g ht t o p u blis h or prese nt i n de pe n d e ntl y t he res ults of t his st u d y i n a gree me nt wit h 
ot her I n vesti gat ors a n d st a ke h ol de rs. T h e I n vesti gat or s hall pr o vi de t he S p o ns or wit h a c o p y of 
a n y s u c h pres e ntati o n or p u blicati o n f or re vie w a n d c o m me nt at least 3 0 da ys i n a d v a nce of a n y 
prese ntati o n or s u b missi o n f or p u blicati o n. I n a d diti o n, if re q ueste d b y t he S p o ns or, a n y 
prese ntati o n or s u b missi o n f or p u blicati o n s hall be dela ye d f or a li mite d ti me, n ot t o e x cee d 
9 0 da ys, t o all o w f or fili n g of a pa te nt a p plicati o n or s uc h ot her j ustifie d meas ures as t he S p o ns or 
dee ms a p pr o priate t o esta blis h a n d preser v e its pr o prietar y ri g hts.  
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 0 6 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 0 6 
T he I n vesti gat or s hall n ot use t he na me(s) of t he S p o ns or a n d/ or its e m pl o yees i n a d vertisi n g or 
pr o m oti o nal material or p u blicati o n wit h o ut t he pri or writte n c o nse nt of t h e S p o ns or. T he S p o ns or 
s hall n ot use t he na me(s) of t he I n vesti gat or a n d/ or t he c olla b orat ors i n a d v ertisi n g or pr o m oti o nal 
material or p u blicati o n wit h o ut ha vi n g recei ve d  his/ her a n d/ or t heir pri or writte n c o nse nt(s). 
T he S p o ns or has t he ri g ht at a n y ti me t o p u blis h t he res ults of t he st u d y. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 0 7 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 0 7 
1 5  
C LI NI C A L T RI A L P R O T O C O L A M E N D M E N T S 
All a p pe n dices attac he d heret o a n d re ferre d t o herei n are ma d e part of t his cli nical  trial pr ot oc ol. 
T he I n vesti gat or s h o ul d n ot i m ple me nt  a n y de viati o n fr o m, or c ha n ges t o t he cli nical trial pr ot oc ol 
wit h o ut a gr ee me nt b y t he S p o ns or a n d pri or re vi e w a n d d oc u me nte d a p pr o val/fa v ora bl e o pi ni o n 
fr o m t he I R B/I E C a n d/ or n otificati o n/a p pr o val of healt h a ut h orities (c o m pete nt re g ulat or y 
a ut h orit y) of a n a m e n d me nt, as re q uire d b y l o cal re g ul ati o n, e x ce pt w here necessar y t o eli mi nate 
a n i m me diate hazar d(s) t o cli nical trial patie nts, or w he n t he c h a n ge(s) i n v ol ves o nl y l o gistical or 
a d mi nistrati ve as pects of t he trial. A n y c ha n ge  a gree d u p o n will be rec or d e d i n writi n g, t he 
writte n a me n d me nt will be si g ne d b y t he I n vest i gat or a n d b y t he S p o ns or a n d t he si g ne d 
a me n d me nt will be file d wit h t his cli nical trial pr ot oc ol. 
A n y a me n d me nt t o t he cli nical trial pr ot oc ol re q uires writte n a p pr o val/fa v ora ble o pi ni o n b y t h e 
I R B/I E C pri or t o its i m ple me ntati o n, u nless t here are o verri di n g safet y reas o ns. 
I n case of s u bsta ntial a m e n d me nt t o t he cli nical trial pr ot oc ol, a p pr o val fr o m t he healt h a ut h orities 
(c o m pete nt r e g ulat or y a ut h orit y) will be s o u g ht bef ore i m ple me ntati o n. 
I n s o me i nsta n ces, a n a m e n d me nt ma y re q uire a c ha n ge t o t he I C F. T h e I n vesti gat or m ust recei v e 
a n I R B/I E C a p pr o val/fa v ora ble o pi ni o n c o ncer ni n g t he re vise d I C F pri or t o i m ple me ntati o n of t he 
c ha n ge a n d patie nt si g n at ure s h o ul d be re-c ollecte d if necessar y. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 0 8 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 0 8 
1 6  
BI B LI O G R A P HI C R E F E R E N C E S 
1.  Cre mer A, A mr a o ui F, Li p G Y, M orales E, R u bi n S, Se g ura J, et al. Fr o m mali g na nt 
h y perte nsi o n t o h y p erte nsi o n- M O D: a m o der n defi niti o n f or a n ol d b ut still da n ger o us 
e mer ge n c y. J H u m H y perte ns. 2 0 1 6; 3 0( 8): 4 6 3- 4 6 6. 
2.  I nter nati o nal Dia b etes Fe derati o n Dia bet es Atlas 7t h E diti o n.  
htt p:// w w w. dia betesatlas. or g/r es o urces/ 2 0 1 5-atlas. ht ml. Accesse d 1 5 J ul y 2 0 1 6 
3.  A merica n Di a betes Ass o ciati o n. A merica n Dia bet es Ass oci ati o n A p pla u ds T w o- Year Re 
A ut h orizati o n of S pecial Dia betes Pr o gra m. A merica n Dia bet es Ass ociati o n. A vaila ble fr o m: 
htt p:// w w w. dia betes. or g/ ne wsr o o m/ press-releas es/ 2 0 1 0/re-a ut h orizati o n-s pecial- dia b etes-
pr o gra m. ht ml. Accesse d J ul y 1 2, 2 0 1 6. 
4.  A merica n Di a betes Ass o ciati o n. Sta n dar ds of Me dical Care i n Di a b etes – 2 0 1 3. Dia betes 
Care. 2 0 1 3 J a n; 3 6( S u p pl 1): S 1 1- S 6 6. 
5.  Casta ne da- Sce p pa C, Casta ne da F. S o di u m- d e pe n de nt gl uc os e tra ns p ort er pr otei n as a 
p ote ntial t hera pe utic tar get f or i m pr o vi n g gl yce mi c c o ntr ol i n dia betes. N utr Re v. 2 0 1 1 Dec; 
6 9( 1 2): 7 2 0- 7 2 9. 
6.  M u dalier S. S o di u m – Gl uc ose C otra ns p orter I n hi bit ors: Effects o n Re nal a n d I ntesti nal 
Gl uc ose Tra ns p ort; Fr o m Be nc h t o Be dsi de. Dia betes Care. 2 0 1 5; 3 8: 2 3 4 4 – 5 3. 
7.  He di ger H A. E x pressi o n cl o ni n g a n d c D N A s e q ue nci n g of t h e Na +/ gl u c ose c o-tra ns p ort er. 
Nat ure. 1 9 8 7; 3 3 0: 3 7 9- 8 1. 
8.  Wri g ht E M. I. Gl uc ose galact ose mala bs or pti o n. A m J P h ysi ol. 1 9 9 8; 2 7 5: G 8 7 9- G 8 8 2. 
9.  K o m or os ki B, Vac h har aj a ni N, Fe n g Y, Li L, K or n ha user D, Pfister M. D a pa glifl ozi n, a 
n o vel, selecti ve S G L T 2 i n hi bit or, i m pr o ve d gl y ce mic c o ntr ol o ver 2 w ee ks i n patie nts wit h 
t y pe 2 dia b etes mellit us. Cli nical P har mac ol o g y & T hera p e utics. 2 0 0 9 Ma y; 8 5( 5): 5 1 3- 9. 
1 0. List J F, W o o V, M orales E, Ta n g W, Fie d ore k  F T. S o di u m- gl uc ose c otra ns p ort i n hi biti o n wit h 
da pa glifl ozi n i n t y p e 2 dia betes. Dia b etes care. 2 0 0 9 A pr; 3 2( 4): 6 5 0- 7. 
1 1. I nz ucc hi S E, Ber ge nstal R M, B use J B, Dia m a nt M, Ferra n ni ni E, Na u c k M, et al. 
Ma na ge me nt of h y p er gl yce mia i n t y p e 2 di a betes: a patie nt-ce ntere d a p pr o ac h p ositi o n 
state me nt of t he A meri ca n Dia betes Ass oci ati o n ( A D A) a n d t h e E ur o pea n Ass ociati o n f or t he 
St u d y of Dia b etes ( E A S D). Di a betes care. 2 0 1 2 J u n; 3 5( 6): 1 3 6 4- 7 9. 
1 2. Ma ncia G, Fa gar d R, Nar k ie wicz K, Re d o n J, Za n c hetti A, B ö h m M, et al. 2 0 1 3 E S H/ E S C 
g ui deli nes f or t he ma na ge me nt of art erial h y pe rt e nsi o n: t he Tas k F orce f or t he Ma na ge me nt of 
Arterial H y p erte nsi o n of t he E ur o pea n S oci et y of H y p erte nsi o n ( E S H) a n d of t he E ur o pea n 
S ociet y of Car di ol o g y ( E S C). E ur Heart J. 2 0 1 3; 3 4( 2 8): 2 1 5 9 – 2 1 9. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 0 9 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 0 9 
1 3. W or k gr o u p o n H y p o gl yce mia, A merica n Dia b et es Ass ociati o n. Defi ni n g a n d re p orti n g 
h y p o gl yce mia i n dia betes: a re p ort fr o m t h e A meri ca n Dia b etes Ass ociati o n W or k gr o u p o n 
H y p o gl yce mia. Dia b etes Care. 2 0 0 5 Ma y; 2 8( 5): 1 2 4 5- 9. 
1 4. F D A G ui da n ce f or I n d ustr y:  Dia b etes Mellit us - De vel o pi n g Dr u gs a n d T hera pe utic Bi ol o gics 
f or Treat me nt a n d Pre v e nti o n. Li nes 1 1 4 4 – 1 2 1 5. A vaila ble fr o m: 
htt p:// w w w.f da. g o v/ d o w nl oa ds/ 
Dr u gs/ G ui da nce C o m plia nce Re g ulat or yI nf or mati o n/ G ui da nces/ U C M 0 7 1 6 2 4. p df. Accesse d 
J ul y 1 2, 2 0 1 6 
1 5. Sea q uist E R, A n ders o n J, C hil ds B, Cr yer P, Da g o ga-J ac k S, Fis h L, et al. H y p o gl yce mia a n d 
Dia betes: A Re p ort of a W or k gr o u p of t h e A meri ca n Dia b etes Ass ociati o n a n d T he E n d ocri ne 
S ociet y. Dia b etes Car e. 2 0 1 3; 3 6( 5): 1 3 8 4- 9 5 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 1 0 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 1 0 
1 7  
A P P E N DI C E S 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 1 1 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 1 1 
A p p e n di x A  
G ui d a n c e o n c o ntr a c e pti v e m et h o d s a n d c oll e ct i o n of pr e g n a n c y 
i nf or m ati o n 
D E FI NI TI O N S 
N o nre pr o d ucti ve p ote nti al 
1.  Pre me n o pa usal f e male wit h 1 of t he f oll o wi n g: 
- 
D oc u me nte d h yster ect o m y 
- 
D oc u me nte d bilateral sal pi n gect o m y 
- 
D oc u me nte d bilater al o o p h orect o m y. 
2.  P ost me n o pa usal 
- 
A p ost me n o pa usal state is defi ne d as n o me ns es f or 1 2 m o nt hs wit h o ut a n alter nati ve 
me dical ca us e. A hi g h F S H le vel i n t he p os t me n o pa usal ra n ge ma y be use d t o c o nfir m 
a p ost me n o pa usal state i n w o me n n ot usi n g h or m o nal c o ntrace pti o n or h or m o ne 
re place me nt t hera p y ( H R T). H o we v er, i n t he a bs e nce of 1 2 m o nt hs of a me n orr hea, a 
si n gle F S H meas ur e me nt is i ns ufficie nt.  
- 
Fe males o n H R T a n d w h ose me n o pa usal stat us is i n d o u bt will be re q uire d t o use 1 of 
t he hi g hl y effecti ve c o ntrace pti o n met h o ds if t he y wis h t o c o nti n ue t heir H R T d uri n g 
t he st u d y. Ot her wise, t he y m ust disco nti n ue H R T t o all o w c o nfir mati o n of 
p ost me n o pa usal stat us bef ore st u d y e nr ol me nt. 
Re pr o d ucti ve p ote nti al  ( W O C B P) 
A w o ma n is c o nsi der e d of re pr o d u cti ve p ote ntial ( W O C B P), ie, fertile, f oll o wi n g me n arc h e a n d 
u ntil bec o mi n g p ost me n o pa usal u nless per ma n e ntl y  sterile. Per ma ne nt sterilizati o n met h o ds 
i ncl u de h ysterect o m y, bil ateral sal pi n gect o m y a n d bilateral o o p h orect o m y. 
C O N T R A C E P TI V E G UI D A N C E 
W o me n of re pr o d ucti ve p ote ntial ( W O C B P) m ust us e a hi g hl y effecti ve m et h o d of c o ntrace pti o n 
d uri n g t he tr eat me nt peri o d a n d t he p ost-treat me nt f oll o w u p perio d ( 2 8 ± 3 da ys). If a n ot her 
c o ntrace pti ve met h o d is use d (s uc h as a barrier m et h o d), it s h o ul d be use d i n c o m bi nati o n wit h 
o ne of t he hi g hl y eff ecti v e met h o ds (s uc h as a n oral c o ntrace pti ve). 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 1 2 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 1 2 
Fe m ale p atie nts: 
Hi g hl y Effecti ve C o ntr ace pti ve Met h o ds T h at Are User De pe n de nt 
F ail ure r ate of < 1 % per ye ar w he n use d c o nsiste ntly a n d c orrectly a 
•  C o m bi ne d (estr o ge n- a n d pr o gest o ge n-c o ntai ni n g ) h or m o nal c o ntrace pti o n ass ociate d wit h 
i n hi biti o n of o v ulati o n 
− oral 
− i ntra va gi nal 
− tra ns der mal 
•  Pr o gest o ge n- o nl y h or m o ne c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n 
− oral 
− i njecta ble 
Hi g hl y Effecti ve Met h o ds T h at Are User I n de pe n de nt 
•  I m pla nta ble pr o gest o ge n- o nl y h or m o ne c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n 
•  I ntra uteri ne de vice (I U D) 
•  I ntra uteri ne h or m o ne-releasi n g s yste m (I U S) 
•  Bilateral t u bal occl usi o n 
•  Vasect o mize d part ner 
( V asect o mize d p art ner is a hi g hly effective c o ntr ace ptive met h o d pr ovi de d t h at t he p art ner is t he 
s ole sex u al p art ner of t he w o m a n of c hil d be ari n g p ote nti al a n d t he a bse nce of s per m h as bee n 
c o nfir me d. If n ot, a n a d diti o n al hi g hly effective met h o d(s) of c o ntr ace pti o n s h o ul d be use d. 
S per m at o ge nesis cycle is a p pr oxi m ately 9 0 d ays.)  
•  Se x ual a bsti ne nce 
( Sex u al a bsti ne nce is c o nsi dere d a hi g hly effective met h o d o nly if defi ne d as refr ai ni n g fr o m 
heter osex u al i nterc o urse d uri n g t he e ntire peri o d of risk ass oci ate d wit h t he st u dy dr u g. T he 
reli a bility of sex u al a bsti ne nce nee ds t o be ev al u ate d i n rel ati o n t o t he d ur ati o n of t he st u dy a n d 
t he preferre d a n d us u al lifestyle of t he p atie nt.) 
N O T E: 
a)  T y pical use fail ure rates ma y differ fr o m t h ose w he n use d c o nsiste ntl y a n d c orrectl y. Use s h o ul d be 
c o nsiste nt wit h l ocal re g ulati o ns re gar di n g t he use of c o ntrace pti ve met h o ds f or patie nts 
partici pati n g i n cli nical st u dies. 
 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 1 3 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 1 3 
C O L L E C TI O N O F P R E G N A N C Y I N F O R M A TI O N 
M ale p atie nts wit h p art ners of re pr o d ucti ve p ote nti al w h o bec o me pre g n a nt  
•  T he I n vesti gat or will atte m pt t o c ollect pre g na nc y i nf or mati o n o n a n y fe mal e part ner of a 
male st u d y patie nt w h o b ec o mes pre g na nt w hile p artici pati n g i n t his st u d y. T his a p plies 
o nl y t o patie nts w h o r ecei ve st u d y treat me nt. 
•  After o btai ni n g t he necessar y si g n e d i nf or me d  c o nse nt fr o m t he pre g n a nt fe male part ner 
directl y, t h e I n vesti gat or will rec or d pre g na nc y i nf or mati o n o n t he a p pr o pri ate f or m a n d 
s u b mit it t o t he S p o ns or wit hi n 2 4 h o urs of lear ni n g of t he part ner’s pre g n a nc y  
•  Part ner will als o be f oll o we d t o deter mi ne t he o ut c o me of t he pre g na n c y. I nf or mati o n o n 
t he stat us of t he m ot her a n d c hil d will be f or war d e d t o t he S p o ns or.  
•  Ge ner all y, f oll o w- u p will be n o l o n ger t ha n 6 t o 8 wee ks f oll o wi n g t he esti mate d deli ver y 
date. A n y ter mi nati o n of t he pre g na n c y will be re p orte d re gar dless of fetal stat us ( prese n ce 
or a bse nce of a n o m alies) or i n dicati o n f or pr o ce d ure  
Fe m ale p atie nts w h o bec o me pre g n a nt  
•  T he I n vesti gat or will c oll ect pre g n a nc y i nf or m ati o n o n a n y fe male p atie nt, w h o bec o mes 
pre g na nt w hile partici pati n g i n t his st u d y  
•  I nf or mati o n will be rec or de d o n t he a p pr o priate f or m a n d s u b mitte d t o t he S p o ns or wit hi n 
2 4 h o urs of lear ni n g of a patie nt's pre g na n c y.  
•  Patie nt will be f oll o we d t o deter mi ne t he o utc o me of t he pre g n a nc y. T he I n vesti gat or will 
c ollect f oll o w- u p i nf or m ati o n o n patie nt a n d ne o n ate, w hic h will be f or war de d t o t he 
S p o ns or. Ge ner all y, f oll o w- u p w ill n ot be re q uire d f or l o n ger t ha n 6 t o 8 wee ks be y o n d t he 
esti mate d deli ver y date.  
•  A n y ter mi nati o n of pre g n a nc y will be re p orte d, re gar dless of fetal stat us ( prese nce or 
a bse nce of a n o malies) or i n dicati o n f or pr oce d ure.  
•  W hile pre g na n c y itself is n ot c o nsi dere d t o be  a n A E or S A E, a n y pre g na n c y c o m plicati o n 
or electi ve ter mi nati o n of a pre g na n c y will be re p orte d as a n A E or S A E.  
•  A s p o nta ne o us a b orti o n is al wa ys c o nsi dere d t o  be a n S A E a n d will be re p orte d as s uc h. 
A n y S A E o cc urri n g as a res ult of a p ost-st u d y pre g na n c y w hic h is c o nsi dere d reas o n a bl y relat e d 
t o t he st u d y treat me nt b y t he I n v esti gat or, will be re p orte d t o t he Sp o ns or as descri be d i n 
Secti o n  1 0. 4. 1. 2 . W hile t he I n vesti gat or is n ot o bli gat e d t o acti vel y see k t his i nf or mati o n i n 
f or mer st u d y patie nts, he or s he ma y lear n of a n S A E t hr o u g h s p o nt a ne o us re p orti n g.  
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 1 4 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 1 4 
A p p e n di x B  
A m b ul at or y bl o o d pr e s s ur e m o nit ori n g s u b st u d y 
B ac k gr o u n d 
A P hase 2 trial of s ota glifl ozi n ( L X 4 2 1 1. 1- 2 0 2) pr o vi de d e vi de nce t hat s ot a glifl ozi n re d uce d b ot h 
S B P a n d D B P i n patie nts wit h el e vate d S B P a n d D B P at Baseli ne b ut n ot n or m ote nsi ve patie nts. 
I n t his s u bst u d y of a p pr o xi matel y 2 0 0 patie nts wit h mea n Scree ni n g S B P ≥1 3 0 m m H g, patie nts 
will ha ve A B P M assess e d f or 2 4 h o urs at Baseli n e, Wee k 1 2, a n d Wee k 2 6 t o pr o vi de a m ore 
s yste matic assess me nt of t he S B P a n d D BP l o weri n g efficac y of s ota glifl ozi n. 
S u b-st u d y pr oce d ures 
Patie nts wit h mea n Scree ni n g S B P ≥1 3 0 m m H g will pr o vi de d wit h i nf or mati o n o n t he A B P M 
s u bst u d y, a n d se p arat e i nf or me d c o nse nt ta ke n bef ore A B P M s u bst u d y-s pecific pr oce d ures are 
perf or me d.  
Patie nts i n t he A B P M s u bst u d y w ill ha ve 3 a d diti o nal visits t o t he site f or place me nt of t he A B P M 
de vice. T hes e will be Visits 3 A, 7 A a n d 9 A. Visit 3 A will occ ur at Wee k - 1, 1 wee k bef ore 
ra n d o mizati o n. Visits 7 A a n d 9 A will occ ur t he d a y bef ore Visit 7 ( Wee k 1 2) a n d Visit 9 
( Wee k 2 6).  
Patie nts d o n ot nee d t o be fasti n g f or Visits 3 A, 7 A a n d 9 A. O nce t he A B P M de vice has b ee n 
place d at Visit 3 A, patie nts will be i nstr ucte d t o re m o ve it 2 4 h o urs later a n d re t ur n it t o t he site b y 
p ost i n a p pr o priate pac ka gi n g pr o vi de d b y t he site. T we nt y-f o ur h o urs aft er Visits 7 A a n d 9 A, 
patie nts will ret ur n t o t he site i n a fasti n g stat e at Visits 7 a n d 9, res pecti vel y, a n d t he d e vice will 
be re m o ve d. All A B P M data will be re vie we d f oll o wi n g ret ur n of t he d e vice t o e ns ure q u alit y of 
t he rec or di n g; p atie nts wit h A B P M data n ot of s ufficie nt q ualit y will be as k e d t o re peat t he 
pr ocess as s o o n as p ossi ble. Patie nts wit h A B P M data n ot of s uffici e nt q ualit y at Visit 3 A s h o ul d 
n ot be ra n d o mize d u ntil t he Bas eli ne A B P M rec or di n g has b ee n re peat e d. 
A m b ulat or y bl o o d pr ess ure m o nit ori n g will be p erf or me d wit h a vali dat e d de vice pr o vi de d b y t h e 
S p o ns or or S p o ns or re prese ntati ve. Eac h rec or di n g will start i n t he m or ni n g prefera bl y bet w ee n 
8: 0 0 a n d 1 0: 0 0 i m me diatel y after t h e a d mi nistrati o n of st u d y me dicati o n, a n d will e n d after at 
least 2 4 h o urs of r ec or di n g o n t he f oll o wi n g day. T he bl o o d press ure c uff will be a p plie d 
prefere ntiall y o n t he n o n- d o mi na nt ar m. T he m o nit or will be pr o gra m me d t o meas ure bl o o d 
press ure e ver y 2 0 mi n utes bet wee n 0 8: 0 0 a n d 2 1: 5 9, a n d e ver y 3 0 mi n utes bet wee n 2 2: 0 0 a n d 
0 7: 5 9. Patie nts will re mai n b li n de d t o all c ollecte d A B P M val ues b y s witc hi n g off t h e dis pla y of 
t he de vice. T h e y will be i nstr ucte d t o f oll o w t heir us ual dail y r o uti nes, b ut t o re mai n still a n d 
a v oi d ar m m o ve me nt d uri n g eac h a ut o mate d m eas ure me nt. Patie nts will be as ke d t o a v oi d 
stre n u o us acti vit y, b at hi n g, or ta ki n g a s h o wer a n d t o rec or d t he ti me of sl ee p a n d a n y u n us ual 
e ve nts or p o or slee p q ualit y d uri n g t he A B P M rec or di n g peri o d i n t heir st u d y l o g. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 1 5 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 1 5 
S u b-st u d y o bjecti ves 
T he pri mar y o bjecti ve of t he A B P M s u bst u d y is t o  c o m pare t he effect of s ot a glifl ozi n vers us 
place b o i n a s u bset of p atie nts wit h mea n S B P ≥1 3 0 m m H g at Scree ni n g o n 2 4- h o ur a vera ge S B P 
at Wee k 1 2. 
T he sec o n d ar y o bjecti ves of t he A B P M s u bst u d y are t o c o m pare t he effect of s ota glifl ozi n vers us 
place b o i n a s u bset of p atie nts wit h mea n S B P ≥1 3 0 m m H g at Scree ni n g o n t he f oll o wi n g: 
•  2 4- h o ur a vera ge S B P at Wee k 2 6 
•  2 4- h o ur a vera ge D B P at Wee ks 1 2 a n d 2 6 
•  A vera ge a dj uste d a wa ke ti me bl o o d press ure ( B P) as meas ure d b y S B P a n d D B P at Wee ks 
1 2 a n d 2 6 wit h a dj ust me nt base d o n acti gra p h y 
•  A vera ge a dj uste d slee pi n g ti me B P as m eas ure d b y S B P a n d D B P at Wee ks 1 2 a n d 2 6 
wit h a dj ust me nt base d o n acti gra p h y. 
S u b-st u d y e n d p oi nts 
T he pri mar y e n d p oi nt of t he s u bst u d y is: 
•  C ha n ge fr o m Baseli ne t o Wee k 1 2 i n a vera ge 2 4- h o ur S B P i n a s u bset of patie nts wit h 
mea n S B P ≥1 3 0 m m H g at Scree ni n g. 
T he sec o n d ar y e n d p oi nts of t he s u bst u d y are: 
•  C ha n ge fr o m Baseli ne t o Wee k 2 6 i n a vera ge 2 4- h o ur S B P 
•  C ha n ge fr o m Baseli ne t o Wee k 1 2 a n d 2 6 i n A vera ge 2 4- h o ur D B P  
•  C ha n ge fr o m Baseli ne t o Wee k 1 2 a n d 2 6 i n a vera ge a dj uste d a w a ke ti me B P as meas ure d 
b y S B P a n d D B P wit h a dj ust me nt base d o n acti gra p h y 
•  C ha n ge fr o m Baseli ne t o Wee k 1 2 a n d 2 6 i n a vera ge a dj uste d slee p ti me B P as meas ure d 
b y S B P a n d D B P wit h a dj ust me nt base d o n acti gra p h y. 
St atistic al a n al yses 
T he q ualit y of a visit rec or di n g will be c o nsi d ere d i ns ufficie nt if t he visit rec or di n g d oes n ot meet 
t he criteria b el o w: 
1.  Visit rec or di n g d oes n ot c o ntai n great er t ha n  or e q ual t o 1 7 n o n-c o nsec uti v e h o urs of dat a 
w here eac h h o ur has at least o ne vali d B P meas ure me nt. 
2.  Visit rec or di n g has less t ha n 4 4 t otal meas ure m e nts. 
A B P M s u bst u d y e n d p oi nts will be a nal yze d usi n g a si milar a p pr oac h as t he pri mar y efficac y 
e n d p oi nt wit h missi n g val ues i m p ute d b y c o ntr ol- base d m ulti ple i m p utati o n met h o d u n der t he 
missi n g n ot at ra n d o m fr a me w or k. E ac h of t h e c o m plete dataset will be a n al yze d usi n g 
A N C O V A m o del i ncl u di n g f act ors f or treat me nt (s ota glifl ozi n, place b o), ra n d o mizati o n strat u m 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 1 6 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 1 6 
of H b A 1c ( ≤8. 0 %, > 8. 0 %) as fi x e d effects, a n d t he baseli ne val u e of t he s pecific de p e n de nt 
varia ble as a c o v ariate. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 1 7 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 1 7 
A p p e n di x C  
T w o- h o ur st a n d ar di z e d mi x e d m e al 
A 2- h o ur P P G will be o btai ne d after a sta n dar d ize d M M i n all patie nts at Baseli ne ( D a y 1, 
Visit 3), at Wee k 2 6 ( Visit 9), a n d at Wee k 7 9 ( Vis it 1 3) or earlier if t he patie nt ter mi nates st u d y 
partici pati o n bef or e Wee k 2 6. A n y p atie nt w h o re q uires t he a d diti o n of res c ue me dicati o n pri or t o 
Wee k 2 6 a n d/ or Wee k 7 9 (see Secti o n 9. 1. 4. 2 ) s h o ul d still ha ve t he sta n dar dize d M Ms perf or me d 
at Wee k 2 6 a n d Wee k 7 9. 
T he sta n dar dize d M M m ust n ot be d o ne w hile pa tie nts are te m p oraril y off I M P; t he Me dical 
M o nit or will a d dress a n y e pis o des o n a case- b y-case basis a n d t he sta n dar dize d M M will be 
resc he d ul e d w he n t he p atie nt ca n res u m e I M P, if a p plica ble. 
T he first d ose of d o u ble- bli n d I M P a n d metf or mi n o n Da y 1 ( Visit 3) will be gi v e n after  
c o m pleti o n of t he 2- h o ur P P G c ollecti o n. F or t h e Wee k 2 6 a n d Wee k 7 9 sta n dar dize d M M, t he 
patie nt s h o ul d ta ke t he d ose of  d o u ble- bli n d I M P i m me diatel y after t he fasti n g bl o o d sa m ples are 
o btai ne d, a n d a p pr o x i matel y 3 0 mi n utes bef ore  i n gesti o n of t he sta n d ar dize d M M be gi ns. At 
Wee k 2 6, metf or mi n is gi ve n after  c o m pleti o n of t he 2- h o ur P P G c ollecti o n. 
St a n d ar d Me al f or t he St a n d ar dize d Mi xe d Me al: 
T he sta n dar d ( brea kfast) meal will be pr o vi de d b y t he S p o ns or as a li q ui d n utriti o n dri n k ( B o ost ® , 
E ns ure ® , or si milar), wit h ~ 4 0 g car b o h y drate a n d ~ 2 4 0 cal ories per b ottle ( ~ 8 o u nces). T he 
cal oric c o m p ositi o n of t h e meal is ~ 6 5 % car b o h y drate, ~ 1 5 % pr otei n, a n d ~ 2 0 % fat. T he a m o u nt 
gi ve n is 6 m L/ k g b o d y w ei g ht u p t o a ma xi m u m of 3 6 0 m L. T h eref ore f or patie nts ≥6 0 k g, t he 
sta n dar d meal c o nsists of ~ 6 0 g car b o h y drate a n d 3 6 0 cal ories.  
Patie nts are i nstr ucte d t o c o m pletel y c o ns u me t h e meal wit hi n 1 5 mi n utes, a n d e ver y eff ort s h o ul d 
be ma de t o c o m plete t he meal wit hi n 2 0 mi n utes after it is starte d. Water or n o ncaffei nate d, 
zer o-cal orie b e vera ges m a y b e c o ns u me d a d li b it u m. N o ot her f o o d ma y be c o ns u me d u ntil t he 
2- h o ur p ost pra n dial plas ma gl uc os e sa m ple has b ee n c ollecte d. If t he p atie nt is u na ble t o c o ns u me 
at least 5 0 % of t he sta n d ar d meal d uri n g t he M M T T at Bas eli ne ( D a y 1, Visit 3), t he patie nt 
s h o ul d n ot be ra n d o mize d. If a M M T T after ra n d o mizati o n is n ot t olerate d, eff ort s h o ul d be ma d e 
t o re peat t he testi n g at t h e discreti o n of t he In vesti gat or. If t he p atie nt  ca n n ot t olerate M M T T u p o n 
re peat testi n g, t his s h o ul d be d oc u me nte d i n t he e- C R F wit h t he reas o n a n d t he patie nt s h o ul d 
c o nti n ue i n t he st u d y. If t he patie nt is a ble  t o c o ns u me > 5 0 % of t he sta n d ar dize d M M, t he 
a p pr o xi mate a m o u nt s h o ul d be rec or de d, a n d a n e q ui vale nt a m o u nt  s h o ul d be c o ns u me d at t he 
s u bse q ue nt sta n dar diz e d M M. 
B aseli ne Visit ( D a y 1, Visi t 3) St a n d ar dize d M M: 
1.  Rec or d t he a m o u nt a n d bra n d na me of t he sta n dar d meal li q ui d n utriti o n dri n k t he patie nt 
is i nstr ucte d t o c o ns u me i n t he s o urce d o c u me nts 
2.  Fasti n g bl o o d sa m ples ar e o btai ne d, i ncl u di n g Ti me 0 fasti n g F P G 
3.  Rec or d t he ti me of bl o o d sa m ple c ollecti o n i n t he s o urce d oc u m e nts 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 1 8 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 1 8 
4.  I m me diat el y after t he fasti n g bl o o d sa m ples are c ollecte d, t he patie nt starts c o ns u mi n g t he 
sta n dar d meal 
5.  Rec or d t he ti me t he meal i n gesti o n starts i n t he s o urce d oc u m e nts 
6.  T he 2- h o ur c o u nt d o w n f or t he 2- h o ur plas ma P P G starts i m me diatel y after t he patie nt 
be gi ns i n gesti o n of t he st a n dar d meal 
7.  T he patie nt is i nstr ucte d t o i n gest t he prescri b e d a m o u nt wit hi n 1 5 t o 2 0 mi n utes. 
8.  Rec or d t he ti me i n gesti o n is c o m plete d, meas ure t he p orti o n of t he meal n ot i n geste d (if 
a n y), a n d r ec or d t h e assesse d perce nt of pr escri be d a m o u nt i n geste d i n t he s o urce 
d oc u me nts 
9.  N o bl o o d sa m ples f or P K are c ollecte d at t his visit 
1 0.  T w o h o urs after t he meal i n gesti o n starts , t he 2- h o ur plas ma P P G is c ollecte d 
1 1.  Rec or d t he ti me t he 2- h o ur plas ma P P G is c ollecte d i n s o urce d o c u me nts 
1 2.  D o u ble- bli n d I M P a n d metf or mi n are a d mi nistere d after  t he bl o o d sa m ple is dra w n at 
1 2 0 mi n utes 
1 3.  Rec or d t he ti me t he d o u ble- bli n d I M P is a d mi nistere d i n t he s o urce d oc u me nts. 
Wee k 2 6 Visit ( Visit 9) a n d Wee k 7 9 ( Visit 1 3) St a n d ar dize d M M: 
1.  Rec or d t he a m o u nt a n d bra n d na me of t he sta n dar d meal li q ui d n utriti o n dri n k t he patie nt 
is i nstr ucte d t o c o ns u me i n t he s o urce d o c u me nts 
2.  Fasti n g bl o o d sa m ples ar e o btai ne d, i ncl u di n g  Ti me 0 F P G a n d pre- d ose P K sa m ples 
3.  Rec or d t he ti me of bl o o d sa m ple c ollecti o n i n t he s o urce d oc u m e nts 
4.  D o u ble- bli n d I M P is a d mi nistere d after  t he fasti n g bl o o d sa m ples are o bt ai ne d 
5.  Rec or d t he ti me t he d o u ble- bli n d I M P is a d mi nistere d i n t he s o urce d oc u me nts 
6.  T hirt y mi n utes aft er t he d o u ble- bli n d I M P is a d mi nistere d, t he patie nt starts c o ns u mi n g t he 
sta n dar d meal 
7.  Rec or d t he ti me t he meal i n gesti o n starts i n t he s o urce d oc u m e nts 
8.  T he 2- h o ur c o u nt d o w n f or t he 2- h o ur P P G star ts i m me diatel y after t he p atie nt be gi ns 
i n gesti o n of t he sta n d ar d meal 
9.  T he patie nt is i nstr ucte d t o i n gest t he prescri b e d a m o u nt wit hi n 1 5 t o 2 0 mi n utes 
1 0.  Rec or d t he ti me i n gesti o n is c o m plete d, meas ure t he p orti o n of t he meal n ot i n geste d 
(if a n y), a n d rec or d t he assesse d perce nt of prescri be d a m o u nt i n geste d i n t he s o urce 
d oc u me nts 
1 1.  T w o h o urs after t he meal i n gesti o n starts , t he 2- h o ur P P G a n d 2- h o ur 3 0 mi n ute P K 
sa m ples are c ollecte d 
1 2.  Metf or mi n is a d mi nistere d after  t he bl o o d sa m ple is dra w n at 1 2 0 mi n utes 
1 3.  Rec or d t he ti me t he 2- h o ur p ost pra n dial bl o o d sa m ples are c ollecte d i n t he s o urce 
d oc u me nts. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 1 9 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 1 9 
A p p e n di x D  
R e c o m m e n d ati o n s o n b a si c g e nit o uri n ar y h y gi e n e, m ai nt ai ni n g 
h y dr ati o n a n d r e c o g ni zi n g di a b eti c k et o a ci d o si s 
Patie nts wit h T 2 D are at ris k f or de vel o pi n g G U i nfecti o ns. T he f oll o wi n g g ui deli nes s h o ul d be 
c o m m u nicate d t o fe mal es a n d u ncirc u mcise d m ales re gar di n g G U i nfecti o ns. Patie nt 
c o m m u nicati o n car ds will be pri nte d wit h t he f oll o wi n g: 
F or fe males: 
“ T he f oll o wi n g a d vice m a y b e usef ul i n hel pi n g y o u t o kee p y o ur bla d der a n d uret hra free fr o m 
i nfecti o n: 
•  G o t o t he t oilet as s o o n as y o u feel t he nee d t o uri nate, rat her t ha n h ol di n g it i n.  
•  Wi pe fr o m fr o nt t o bac k after g oi n g t o t he t oilet.  
•  Practice g o o d h y gie n e b y was hi n g y o ur ge nitals e v er y da y, a n d b ef ore ha vi n g se x.  
•  E m pt y y o ur bla d d er after ha vi n g s e x.”  
F or u ncirc u mcise d males: 
“ T he f oll o wi n g a d vice m a y b e usef ul i n hel pi n g y o u t o kee p t he f ores ki n free fr o m i nfecti o n: 
•  Was h t he e n d of y o ur pe nis a n d f ores ki n wit h  s oa p a n d water ( d o n ot let s oa p get i n t he 
o pe ni n g).  
•  After y o ur s h o w er or b at h, dr y t he e n d of y o ur  pe nis a n d f ores ki n pr o p erl y a n d re place t he 
f ores ki n.  
•  Als o, w he n y o u uri nate, sli de t he f ores ki n bac k e n o u g h s o t hat uri ne d o es n ot get o n t he 
f ores ki n-t his hel ps t o kee p it clea n.” 
M ai nt ai ni n g H y dr ati o n: 
S o di u m- gl uc ose c otr a ns p orter t y pe 2 i n hi bit ors are ass ociate d wit h os m otic di uresis a n d v ol u me 
de pleti o n, w hic h ma y lea d t o dizz i ness or h y p ote nsi o n, es peciall y i n t he el d erl y. Bef ore i nitiati n g 
st u d y dr u g ( at Scree ni n g, R u n-i n a n d Ra n d o mizati o n) a n d d uri n g all o n-site stu d y visits t hereaft er, 
assess v ol u me stat us i n patie nts wit h  re nal i m pair me nt, t he el derl y, i n patie nts wit h l o w S B P, or if 
recei vi n g di ur etics, a n gi ote nsi n-c o n verti n g-e nz y m e i n hi bit ors, or a n gi ote nsi n rece pt or bl oc kers. 
All patie nts will be a d vise d t o mai ntai n pr o per fl ui d i nta ke a n d t o c o nsi der i ncreasi n g it if t he y 
se nse greater t hirst, m ore uri ne pr o d uctio n, or if t h e y feel dizz y or fai nt. 
Patie nt c o m m u nicati o n car ds will be pri nte d wit h t he f oll o wi n g f or patie nts wit h T 2 D: 
“ T he f oll o wi n g a d vice m a y b e usef ul i n hel pi n g y o u t o mai ntai n pr o pe r h y drati o n a n d pre v e nt 
de h y drati o n: 
•  De h y drati o n is w he n y o ur b o d y l oses t o o m u c h fl ui d, fre q ue ntl y d ue t o diarr hea or 
i ncreas e d uri nati o n 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 2 0 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 2 0 
•  C o nsi der i ncreasi n g t he a m o u nt of fl ui ds y o u dri n k if: 
- 
Y o u se nse gr eater t hirst t ha n us ual 
- 
Y o u ha ve a dr y m o ut h or crac k e d li ps 
- 
Y o u ha ve a fe ver 
- 
Y o u ha ve diarr hea or v o miti n g  
- 
Y o u uri nate m ore fre q u e ntl y or i n lar ger a m o u nts t ha n us ual 
- 
Y o u get u p i n t he mi d dle of t he ni g ht t o uri nat e ( m ore t ha n us ual) 
- 
Y o u feel dizz y or li g ht- h ea de d 
- 
Y o u e x ercise, or w h e n it is h ot o utsi de”.  
Rec o g nizi n g D K A 
P ote ntial GI a d v erse e ve nts occ urri n g wit h s ota glifl ozi n ma y m as k pres e nti n g s y m pt o ms of D K A. 
Patie nt c o m m u nicati o n car ds will be pri nte d wit h t he f oll o wi n g: 
“If y o u ha v e a n y of t hese s y m pt o ms o n t he list, t he n c o ntact y o ur st u d y site i m me diatel y f or 
assista nce wit h ma na gi n g y o ur dia betes: 
•  I n a bilit y t o mai ntai n oral i nta ke 
•  Ge ner alize d wea k ness 
•  A b d o mi nal ( bell y) pai n 
•  I n crease d w ei g ht l oss 
•  Fe ver 
•  Fre q u e nt uri nati o n, i ncl u di n g at ni g ht 
•  Fr uit y-sce nte d breat h 
•  C o nf usi o n 
•  Ac ute ill ness 
•  C o nsiste ntl y el e vate d bl o o d gl uc os e 
•  Feeli n g ver y t hirst y or dri n ki n g a l ot 
•  Na usea or v o miti n g 
•  Ha vi n g tr o u ble t hi n ki n g clearl y or feeli n g tire d. 
It is p ossi ble t o ha ve D K A e ve n if y o ur bl o o d gl u c ose is n ot ele vate d. Re gar dless of y o ur bl o o d 
gl uc ose l e vel, if y o u ha v e a n y of t hes e s y m pt o ms o n t he list, t he n c o ntact y o ur st u d y site 
re gar di n g t he n ee d t o be e val uate d f or p ossi ble D K A, w hic h will i ncl u de s pecific bl o o d testi n g. If 
y o ur st u d y site is cl ose d a n d y o ur st u d y d o ct or is  n ot a vaila ble, g o t o t he n earest e mer ge n c y r o o m 
f or e val u ati o n. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 2 1 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 2 1 
If y o u ar e sc he d ul e d f or a pr oce d ure or s ur ger y t hat re q uires y o u t o n ot ta k e a n y f o o d or li q ui ds, 
please c o ntact y o ur st u d y d oct or f or i nstr ucti o ns o n c o nti n ui n g st u d y dr u g. I n s u c h cas es y o ur 
st u d y d oct or ma y a d vise y o u N O T t o ta ke y o ur stu d y dr u g fr o m t he da y pri or t o t he pr oce d ure or 
s ur ger y u ntil after t h e pr o ce d ure or s ur ger y is c om plete, a n d y o u are ta ki n g f o o d a n d li q ui ds as 
y o u n or m all y d o.” 
W he ne ver A E d ata is c ollecte d or t he p atie nt  re p orts D K A or i nterc urre nt ill ness (i ncl u di n g 
i nfecti o ns), ge neralize d wea k ness, i ncreas e d wei g ht l oss, GI s y m pt o ms i ncl u di n g na us ea, 
v o miti n g, or a b d o mi nal p ai n or ot her s y m pt o ms or  si g ns t hat t he I n vesti gat or belie ves ma y b e 
c o nsiste nt wit h D K A, t he n t he site will deter mi ne if a n assess me nt f or D K A is a p pr o priate. If 
la b orat or y testi n g c o nfir ms prese nce of meta b olic aci d osis, t he n t he “ P ossi ble D K A” e- C R F will 
be c o m plete d. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 2 2 of 3 6 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol N o. 0 2  
1 9- D e c- 2 0 1 7 
E F C 1 4 8 3 4 - s ot a glifl o zi n 
V er si o n n u m b er: 1 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al 
P a g e 1 2 2 
A p p e n di x E  
M e a s ur e m e nt of Bl o o d Pr e s s ur e a n d P ul s e R at e 
T he B P meas ure me nt de vice s h o ul d be cali brate d acc or di n g t o ma n ufact urer i nstr ucti o ns.  
E q ui p me nt 
1.  Bl o o d press ur e meas ure me nts will be ta ke n b y  a n a ut o mate d bl o o d press ure m o nit or or a 
ma n ual s p h y g m o ma n o m eter 
2.  Bla d der Le n gt h – S h o ul d nearl y or c o m pletel y e ncircle t he patie nt’s ar m. F or ma n y a d ults, 
t he sta n dar d “a d ult” size bla d der is n ot lo n g e n o u g h a n d t he “lar ge” size bla d der is 
rec o m me n de d 
3.  Bla d der Wi dt h – S h o ul d be at l east 4 0 % of t h e bla d der le n gt h. 
P ati e nt F act o rs 
E xtra ne o us varia bles ass ociate d  wit h t he meas ure me nt of B P s h o ul d be mi ni mize d. T hese i ncl u de: 
1.  F o o d i nta ke, caff ei ne- c o ntai ni n g be v era ges,  ci garette s m o ki n g, or stre n u o us e x ercise 
wit hi n 2 h o urs pri or t o meas ure m e nt 
2.  F ull uri nar y bla d d er 
3.  T he patie nt s h o ul d n ot be all o we d t o tal k w hile B P is bei n g meas ure d 
4.  T he patie nt s h o ul d be place d i n t he e x a mi nati o n r o o m a n d t he c uff s h o ul d b e place d o n t h e 
patie nt’s n o n d o mi na nt ar m. T he pr o per size d c uff s h o ul d fit s n u gl y wit h t he l o wer e d ge 2 
t o 3 c m a b o ve t he a nt ec u bital f ossa. 
5.  T he patie nt s h o ul d be all o we d t o sit q uietl y i n a c o mf orta bl y war m place (t e m perat ure 
ar o u n d 2 5° C or 7 7° F) f or 5 mi n utes wit h t he ar m s u p p orte d at heart le vel, prefera bl y wit h 
t he c uff i n place a n d wit h n o restricti ve clot hi n g o n t he ar m. T he p atie nt s h o ul d be 
e nc o ura ge d n ot t o te nse his or her m uscles. 
N o n d o mi n a nt Ar m 
T he patie nt’s n o n d o mi na nt ar m s h o ul d be t he ar m d eclare d b y t he patie nt as bei n g n o n d o mi na nt. 
T he n o n d o mi na nt ar m s h o ul d t he n be use d f or all s eate d B P meas ure m e nts t hr o u g h o ut t he st u d y. 
Me as ure me nt Tec h ni q ue 
F oll o wi n g t he 5- mi n ute r est peri o d, 3 se parate seate d B Ps s h o ul d be meas ure d wit h at least 
1 mi n ute bet wee n B P meas ure me nts a n d wit h t he c uff f ull y deflate d bet w ee n meas ure me nts. 
All 3 B Ps will be rec or d e d i n t he patie nt’s e- C R F. T he mea n of t h e 3 seate d B Ps will c o nstit ute 
t he B P val ue f or t hat visit. 
T hree seate d p ulse rate m eas ure m e nts will be o btai ne d. T he mea n of t he 3 s eate d p ulse rate 
meas ure me nts will c o nstit ute t he p ulse rate v al ue f or t hat visit. 
( el e ctr o ni c 
 
 
 
2. 0)
( el e ctr o ni c 
 
 
 
1. 0)
Pa ge 1 2 3 of 3 6 0