Investigation of Efficacy and Safety of NNC0165-1875 as add-on to Semaglutide for Weight Management in Subjects With Obesity
Phase: PHASE2
Conditions: Obesity
Sponsor: Novo Nordisk A/S

C o ver P a ge  f or Pr ot oc ol  
S p o ns or na me:  
N o v o N or dis k A/ S  
N C T n u m ber  
N C T 0 4 9 6 9 9 3 9  
S p o ns or t rial I D: 
N N 9 7 7 5 -4 7 0 8  
Official title of st u d y:  
I n vesti gati o n of efficac y a n d safet y of N N C 0 1 6 5-1 8 7 5 as a d d -
o n t o se ma gl uti de f or wei g ht ma na ge me nt i n s u bjects wit h 
o besit y  
D oc u me nt date:  
0 5 A pril 2 0 2 2  

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
Stat us:  
Fi n al  
P a ge:  
1  of 1 1 6  
Pr ot oc ol
P r ot o c ol  titl e: I n v esti g ati o n of effi c a c y a n d s af et y of N N C 0 1 6 5 -1 8 7 5 as a d d -o n t o 
s e m a gl uti d e f o r w ei g ht  m a n a g e m e nt i n s u bj e cts wit h o b esit y  
S u bst a nce: N N C 0 1 6 5 -1 8 7 5  
U ni vers al Tri al N u m ber:  U 1 1 1 1 -1 2 5 4 -9 0 4 6  
E u dr a C T N u m ber:  
I N D N u m ber: 1 3 9, 5 9 2 
Tri al p h ase: 2 a  
I n t he f oll o wi n g, N o v o N or dis k A/ S a n d its affiliates will be state d as “ N o v o N or dis k”. 
T his c o nfi de ntial d oc u me nt is t he pr o pert y of N o v o N or dis k. N o u n p u blis he d i nf or mati o n c o ntai ne d herei n ma y be 
discl ose d wit h o ut pri or writte n a p pr o val fr o m N o v o N or dis k. Access t o t his d oc u me nt m ust be restricte d t o rele va nt 
parties.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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  Pr ot oc ol  versi o n 4. 0
1
1 1 6
T his c o nfi de ntial d oc u me nt is t he pr o pert y of N o v o N or dis k. N o u n p u blis he d i nf or mati o n c o ntai ne d herei n ma y be 
discl ose d w it h o ut pri or writte n a p pr o val fr o m N o v o N or dis k. Access t o t his d oc u me nt m ust be restricte d t o rele va nt 
parties.
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
Stat us:  
Fi n al  
P a ge:  
2  of 1 1 6  
P r ot oc ol a me n d me nt  s u m m ar y of c h a n ges t a ble 
D O C U M E N T HI S T O R Y  
D oc u me nt versi o n  
D ate  
A p plic a ble i n c o u ntry( -ies) a n d/ or site(s) 
Pr ot oc ol versi o n 4. 0  
0 5  A pril  2 0 2 2  
U S A  
Pr ot oc ol versi o n 3. 0  
0 3  N o ve m ber  2 0 2 1  
U S A  
Ori gi nal P r ot oc ol versi o n 2. 0 
1 1 Marc h 2 0 2 1  
Pr ot oc ol ve rsi o n 4. 0 ( 0 5  A pril  2 0 2 2)  
O verall rati o nale f or pre p ari n g pr ot oc ol, versi o n 4. 0:  
T he o verall rati o nale f or t his pr ot oc ol a me n d me nt was  t o u p date t h e d ose a n d d osi n g re gi me n f or 
part 2 b, f oll o wi n g t h e safet y a n d t olera bilit y e val u ati o n of part 1.  
Safet y d ata f or t he 2 . 0 m g d ose of N N C 0 1 6 5 -1 8 7 5 were n ot a vaila ble fr o m part 1 of t he trial d ue t o 
treat me nt disc o nti n uati o n attri b ute d t o t olera bilit y iss ues wit h t he d ose escal ati o n re gi me n use d i n 
part  1.  T he l o wer starti n g d ose a n d t he d ose escalati o n re gi me n us e d f or t he 1. 0 m g N N C 0 1 6 5 -1 8 7 5 
d ose gr o u p a p peare d t olera ble.  Base d o n p art 1,  t h e N o v o N or dis k Safet y C o m mittee has deci de d t o 
u p date part 2 b b y  l o weri n g t he starti n g d ose t o 0. 0 5 m g  N N C 0 1 6 5 -1 8 7 5/ place b o , b y a d di n g  e xtra 
ste ps i n t he d os e escal ati o n re gi me n a n d b y c h a n gi n g t he mai nte n a nce d os e t o 1. 0 m g fr o m 2. 0 m g 
N N C 0 1 6 5 -1 8 7 5/ place b o . I n a d diti o n, t w o e xtra treat me nt ar ms ha ve b ee n a d de d  f or safet y 
e val uati o n of t he 2. 0 m g d ose of N N C 0 1 6 5 -1 8 7 5 , i n w hic h 1 2  s u bjects will be ra n d o mise d 2: 1 t o 
2. 0 m g N N C 0 1 6 5 -1 8 7 5/ place b o . T he s a me l o w st arti n g d os e ( 0. 0 5 mg) a n d d ose escal ati o n re gi m en  
will be use d f or t he 1. 0 m g a n d t he 2. 0  m g  N N C 0 1 6 5 -1 8 7 5 / place b o tr eat me nt ar ms. Bas e d o n t he 
c ha n ges  t o t he d ose escal ati o n re gi me n, tw o a d diti o nal site visits  ( V 1 3 b a n d V 1 4c) a n d o n e 
a d diti o nal p h o ne visit ( P 1 4 b) ha ve bee n a d d e d t o part 2 b . F urt h er m ore, t h e r u n -i n peri o d wit h 
se ma gl uti de h as bee n e xte n de d, beca use t he a d diti o nal visits V 9. 1 a n d V 9. 2 ha ve bee n acti vate d.  
A d diti o nall y , the pr ot oc ol  has bee n u p date d wit h t he i nf or mati o n t hat f o ur of t he la b orat or y assa ys 
use d i n t he trial are f or researc h us e o nl y, he nce  data will  n ot be s hare d wit h t he sites b ut will be 
tra nsferre d dir ectl y t o N o v o N or dis k.  
Secti o n # a n d n a me  Descri pti o n  of c h a n ge  
Brief r ati o n ale  
T hr o u g h o ut t he 
pr ot oc ol  
N N C 0 1 6 5 -1 8 7 5/ place b o  2. 0  m g  1. 0 m g  
Visit 1 0  (r a n d o mis ati o n): Wee k 2 4  Wee k 3 2  
E n d -of -tre at me nt visit: Wee k 4 0  Wee k 4 8  
P art 2 b has bee n u p date d t o 
a l o wer mai nte na nce d ose of 
1. 0  m g  N N C 0 1 6 5 -
1 8 7 5/ place b o  f or efficac y 
a n d safet y e val uati o n of 
N N C 0 1 6 5 -1 8 7 5 .  
F urt her m ore , at s mall c o h ort 
will be ra n d o mise d  t o t he 
2. 0 m g d ose  of N N C 0 1 6 5 -
1 8 7 5/ place b o f or safet y 
e val uati o n of N N C 0 1 6 5 -
1 8 7 5 2. 0 m g .  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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  Pr ot oc ol  versi o n 4. 0
2
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
Stat us:  
Fi n al  
P a ge:  
3  of 1 1 6  
Secti o n # a n d n a me  Descri pti o n  of c h a n ge  
Brief r ati o n ale  
T he a d diti o nal r u n-i n visits 
V 9. 1 a n d V 9. 2 ha ve bee n 
acti vate d, he nce wee k 
n u m bers a n d d urati o ns of 
part 2 ha ve bee n u p date d.  
Secti o n 1. 1  S y n o psis  T o c o m pare t he safet y a n d t ol era bilit y of N N C 0 1 6 5 -1 8 7 5 1. 0 m g 
a n d N N C 0 1 6 5 -1 8 7 5 2. 0 m g  a d de d o n t o se ma gl uti de s.c. 2. 4  m g 
…  
P art 2 is a 4 0  4 8 -wee k, ra n d o mise d f o ur-ar me d , d o u ble-bli n de d 
( wit hi n ar ms), r a n d o mise d, place b o-c o ntr olle d, t w o-ar me d,  
m ulti -ce ntre, pr o of -of -pri nci pl e trial c o m pari n g o nce wee kl y 
N N C 0 1 6 5 -1 8 7 5 as a d d o n t o o nce -wee kl y se ma gl uti de s.c. 2. 4 
m g vers us place b o as a d d o n t o o nce wee kl y se ma gl uti de s.c. 2. 4 
m g i n s u bj ects wit h o besit y . 
I n p art 2 b, 1 2 s u bjects will be r a n d o mise d 2: 1 t o t he 2. 0 m g 
N N C 0 1 6 5 -1 8 7 5/ pl ace b o ar ms, f or s afet y e v al u ati o n of t he 2. 0 
m g d ose. T he re m ai ni n g s u bjects will be r a n d o mise d 2: 1 t o 
t he 1. 0 m g N N C 0 1 6 5 -1 8 7 5/ pl ace b o ar ms f or e v al u ati o n of 
effic ac y a n d s afet y of N N C 0 1 6 5 -1 8 7 5.  
At  wee k 2 4  visit 1 0 , t he s u bj ects e nter P art 2 b; i n a d diti o n t o 
recei vi n g se ma gl uti de s.c. 2. 4 m g, eli gi ble s u bj ects f ulfilli n g all 
ra n d o misati o n criteria at visit 2  will be ra n d o mise d as f oll o ws: 
1 2 s u bjects will be r a n d o mis e d 2: 1 t o recei ve N N C 0 1 6 5 -1 8 7 5 
2. 0  m g or pl ace b o 2. 0  m g a n d t he re mi n der of s u bjects will be 
r a n d o mise d  ( 2: 1) t o recei ve N N C 0 1 6 5-1 8 7 5 2. 0  m g  1. 0  m g  or 
2. 0  m g  place b o 1. 0  m g . T he starti n g d ose of NN C 0 1 6 5 -1 8 7 5 is 
0. 2 5  m g  0. 0 5 m g  a n d d ose esc alati o n wit h N N C 0 1 6 5 -1 8 7 5 or 
N N C 0 1 6 5 -1 8 7 5  place b o will be perf or me d e ver y sec o n d we e k t o 
re ac h t he mai nte na nce d ose s of 1. 0 m g or 2. 0 m g . 
Safet y e val uati o n of t he 2. 0 
m g d ose of N N C 0 1 6 5 -1 8 7 5 
was n ot p ossi ble i n part 1, 
d ue t o treat me nt 
disc o nti n uati o n i n t he 
2. 0  m g d ose  gr o u p . 
F or t hat reas o n  t w o e xtra 
treat me nt ar ms ha ve bee n 
a d de d t o part 2 b, i n w hic h  
1 2 s u bj ects will be 
ra n d o mise d 2: 1 t o t he 2. 0 
m g d ose of N N C 0 1 6 5 -
1 8 7 5/ place b o f or safet y 
e val uati o n.  
Secti o n 1. 2  Fl o wc hart  
* *If visit A d diti o n al visits  9. 1 a n d 9. 2 h a ve bee n acti v ate d  are ne e de d 
b ot h visits will mi mic visit 9 . 
i P Y Y m ai nte n a nce peri o d f or 1. 0 m g N N C 0 1 6 5 -1 8 7 5/ pl ace b o a n d 
P Y Y d os e esc al ati o n a n d m ai nt e n a nce peri o d f or 2. 0 m g N N C 0 1 6 5 -
1 8 7 5/ pl ace b o  
T o matc h t he ne w d osi n g 
re gi me n i n part 2 b, tw o ne w  
site visits ( V 1 3 b a n d V 1 4 c) 
a n d o ne ne w p h o ne visit 
( P 1 4 b) ha ve bee n  a d de d  t o 
t he fl o wc hart, a n d t he p h o ne 
visits P 1 5 a n d P 1 7 ha ve 
bee n m o ve d t o occ ur o ne 
wee k  after a site visit  
i nstea d of t w o wee ks after. 
F urt her m ore, t he wee k 
n u m bers ha ve bee n u p date d 
t o reflect t hat V. 9. 1 a n d 
V 9. 2 ha ve bee n acti vate d .  
Secti o n 2. 1  Trial 
rati o nale 
T he i nitial r u n -i n peri o d i n P art 2 of t he trial ( P art 2a) all o ws f or 
wei g ht l oss t o be o btai ne d wit h se ma gl uti de s.c. 2. 4 m g, bef ore 
t he a d diti o n of N N C 0 1 6 5-1 8 7 5 2. 0 m g  1. 0 m g  t h us all o wi n g f or 
a n y a d diti o nal wei g ht l oss o btai ne d b y t his a d diti o n t o be 
c o m pare d wit h t he wei g ht l oss o btai ne d wit h c o nti n ui n g 
se ma gl uti de s.c. 2. 4 m g o nl y. F urt her m ore, s afet y e v al u ati o n 
of t he N N C 0 1 6 5 -1 8 7 5 2. 0 m g d ose will be perf or me d i n a i n a 
s m all c o h ort. T his trial will pr o vi de pr o of of pri nci ple a n d 
s afet y e v al u ati o n t o g ui de f urt her cli nical de vel o p me nt. 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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V V- T M F- 5 0 4 2 3 4 5
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1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4  of 1 1 6  
 
Secti o n # a n d n a me  Descri pti o n  of c h a n ge  
Brief r ati o n ale  
Secti o n 3. 2. 1  Pri mar y 
e n d p oi nt  
Pri m ar y e n d p oi nt f or N N C 0 1 6 5 -1 8 7 5 1. 0 m g as a n a d d o n t o 
se m a gl uti de 2. 4 m g vers us pl ace b o 1. 0 m g  as a n a d d o n t o 
se m a gl uti de 2. 4 m g: 
Pri mar y e n d p oi nt will be 
e val uate d f or t he 1. 0 m g 
d ose of N N C 0 1 6 5 -1 8 7 5  
Secti o n 3. 2. 2. 2  
S u p p orti ve sec o n dar y 
e n d p oi nts  
S u p p orti ve sec o n d ar y e n d p oi nts f or N N C 0 1 6 5 -1 8 7 5 1. 0 m g 
as a n a d d o n t o se m a gl uti de 2. 4 m g vers us pl ace b o 1. 0 m g  as 
a n a d d o n t o se m a gl uti de 2. 4 m g:  
S u p p orti ve sec o n d ar y e n d p oi nts f or N N C 0 1 6 5 -1 8 7 5 1. 0 m g 
or 2. 0 m g as a n a d d o n t o se m a gl uti de 2. 4 m g vers us pl a ce b o 
1. 0 m g or 2. 0 m g as a n a d d o n t o se m a gl uti de 2. 4 m g:  
T a ble wi t h s u p p orti ve 
sec o n dar y e n d p oi nts has 
bee n di vi de d i n t w o t o 
disti n g uis h  bet wee n 
e n d p oi nts rele va nt f or t he 
1. 0 m g d ose, a n d e n d p oi nts 
rele va nt f or b ot h 1. 0 m g a n d 
2. 0 m g d oses of N N C 0 1 6 5 -
1 8 7 5 . 
Secti o n 4. 1  O verall 
desi g n  
P art 2 is a 4 0  4 8 -wee k, ra n d o mise d f o ur-ar me d , d o u ble-bli n de d 
( wit hi n ar ms), r a n d o mise d, place b o-c o ntr olle d, t w o-ar me d,  
m ulti -ce ntre, pr o of -of -pri nci pl e trial c o m pari n g o nce wee kl y 
N N C 0 1 6 5 -1 8 7 5 2. 0 m g …  
P art 2 will e v al u ate effic ac y a n d s afet y f or N N C 0 1 6 5 -1 8 7 5 
1. 0  m g, a n d s afet y f or N N C 0 1 6 5 -1 8 7 5 2. 0 m g.  
 
At wee k  2 4  3 2 , s u bj ects… will e nter P art 2 b a n d be ra n d o mise d 
i n a 2: 1 ma n ner t o recei ve eit her o nce-wee kl y N N C 0 1 6 5 -1 8 7 5 
2. 0  1. 0 m g or N N C 0 1 6 5 -1 8 7 5  place b o 1. 0 m g  as a d d -o n t o o nce -
wee kl y se ma gl uti de 2. 4 m g. P art 2 b i ncl u des 6  8  wee ks of 
N N C 0 1 6 5 -1 8 7 5  2. 0 m g /N N C 0 1 6 5 -1 8 7 5  place b o  1. 0 m g  d ose 
escalati o n f oll o we d b y 1 0  8  wee ks of N N C 0 1 6 5 -1 8 7 5  2. 0 
m g /N N C 0 1 6 5 -1 8 7 5  place b o 1. 0 m g mai nte na nce u ntil e n d -of -
treat me nt. I n p art 2 b, a s m all c o h ort (1 2  s u bjects) will be 
r a n d o mise d 2: 1 t o N N C 0 1 6 5 -1 8 7 5/ pl ace b o 2. 0 m g, t hese 
s u bjects will h a ve 1 0 w ee ks of d ose esc al ati o n f oll o w e d b y 6 
w ee ks o n N N C 0 1 6 5 -1 8 7 5/ pl ace b o  2. 0  m g  m ai nte n a nce u ntil 
e n d-of -tre at me nt. F or all gr o u ps,  V v isits will ta ke place e ver y 
2  wee ks d uri n g N N C 0 1 6 5 -1 8 7 5 2. 0 m g/ N N C 0 1 6 5 -1 8 7 5 place b o  
d ose escalati o n a n d alter nati n g visits/ p h o ne c o ntacts will ta ke 
place e ver y 2 wee k s f or t he re mai ni n g peri o d u ntil e nd -of -
treat me nt. 
 
I n pr ot oc ol v ersi o n 4. 0, t he t w o a d diti o n al r u n-i n visits ( V 9. 1 
a n d V 9. 2) h a ve bee n acti v ate d.  
T he trial desi g n descri pti o n 
a n d  fi g ure have  bee n 
u p date d  wit h t he ne w d ose  
a n d d ose escalati o n  re gi me n 
f or N N C 0 1 6 5 -1 8 7 5/ place b o 
i n part 2 b. T w o e xtra 
treat me nt ar ms ha ve bee n 
a d de d f or t he 2. 0  m g d ose  
N N C 0 1 6 5 -1 8 7 5/ place b o . 
F urt her m ore , t he wee k 
n u m bers ha ve bee n u p date d 
t o reflect t hat V 9. 1 a n d 
V 9. 2 ha ve bee n acti vate d.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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V V- T M F- 5 0 4 2 3 4 5
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1
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 of
  Pr ot oc ol  versi o n 4. 0
4
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
Stat us:  
Fi n al  
P a ge:  
5  of 1 1 6  
Secti o n # a n d n a me  Descri pti o n  of c h a n ge  
Brief r ati o n ale  
Secti o n 4. 2  Scie ntific 
rati o nale f or trial 
desi g n  
F urt her m ore, t he tri al desi g n will all o w f or e v al u ati o n of 
s afet y, t oler a bilit y a n d P K pr o perties i n t he N N 0 1 6 5-1 8 7 5 2. 0 
m g d ose  gr o u p . 
T he ne w treat me nt ar ms i n 
part 2 b, wit h 2. 0 m g 
N N C 0 1 6 5 -1 8 7 5/ place b o 
will c o ntri b ute t o e val u ati o n 
of t he safet y, t olera bilit y 
a n d P K pr o perties f or 
N N C 0 1 6 5 -1 8 7 5.  
Secti o n 4. 3  
J ustificati o n f or d ose 
I n p art 1 of t his tri al ( N N 9 7 7 5-4 7 0 8), s afet y, t oler a bilit y a n d 
P K pr o perties w ere t o be e x pl ore d f or b ot h 1. 0 m g a n d 2. 0 
m g N N C 0 1 6 5 -1 8 7 5/ pl ace b o. H o w e ver, d at a f or t he 2. 0 m g 
d ose of N N C 0 1 6 5 -1 8 7 5 w ere n ot a v ail a ble fr o m p art 1 of t he 
tri al, d ue t o tre at me nt disc o nti n u ati o n attri b ute d t o 
t oler a bilit y iss ues wit h t he d ose esc al ati o n re gi me n use d i n 
p art 1. T he l o w er st arti n g d ose a n d t he d ose esc al ati o n 
re gi me n use d f or t h e 1. 0 m g N N C 0 1 6 5 -1 8 7 5 d ose gr o u p 
a p pe a re d t oler a ble. B ase d o n p art 1, t he f oll o wi n g c h a n ges 
are m a de f or p art 2 b i n Pr ot oc ol versi o n 4. 0: t he N o v o 
N or dis k S afet y C o m mittee h as deci de d t o u p d ate p art 2 b b y 
l o w eri n g t he st arti n g d ose t o 0. 0 5 m g N N C 0 1 6 5-
1 8 7 5/ pl ace b o, b y a d di n g e xtr a ste ps i n t he d ose esc al ati o n 
re gi me n a n d b y c h a n gi n g t h e m ai nte n a nce d ose t o 1. 0 m g 
N N C 0 1 6 5 -1 8 7 5/ pl ace b o. I n a d diti o n, t w o e xtr a tre at me nt 
ar ms h a ve bee n a d de d f or s afet y e v al u ati o n of t he 2. 0 m g 
d ose of N N C 0 1 6 5 -1 8 7 5, i n w hic h 1 2 s u bjects will be 
r a n d o mise d 2: 1 t o 2. 0 m g N N C 0 1 6 5 -1 8 7 5/ pl ace b o.  
T he j ustificati o n f or d ose 
secti o n has bee n u p date d t o 
i ncl u de i nf or mati o n a b o ut 
t he c ha n ges ma de t o part 2 b. 
Secti o n 6. 1  
Treat me nts 
a d mi nistere d  
…  d ose escalati o n ma y be p ost p o ne d b y o ne  1 -2  wee k s at t he 
discreti o n of t he i n vesti gat or.  
F or p art 1;  b ot h N N C 0 1 6 5 -1 8 7 5/ place b o a n d se ma gl uti de 
s h o ul d be re d uce d if t he s u bj ect d oes n ot t olerate t he ra n d o mise d 
tar get d ose. 
F or p art 2 b; N N C 0 1 6 5 -1 8 7 5/ pl ace b o s h o ul d be re d uce d if t he 
s u bject d oes n ot t oler ate t he r a n d o mise d t ar get d ose. 
Se m a gl uti de s h o ul d p refer a bl y st a y at 2. 4 m g b ut is all o w e d 
t o be re d uce d, as per i n vesti g at or’s discreti o n 
I n T a ble 6 -5,  d osi n g details 
f or N N C 0 1 6 5-1 8 7 5/ place b o 
i n part 2 b, ha ve  bee n 
u p date d t o t he ne w  d osi n g 
re gi me n a n d ne w wee k 
n u m bers  f or t he 1. 0  m g a n d 
2. 0 m g ar ms . 
Clarificati o n of t he differe nt 
d ose re d ucti o n a p pr oac hes 
f or part 1 c o m pare d wit h  
part 2 b of t he trial.  
Secti o n 6. 3  Meas ure 
t o mi ni mise bias: 
Ra n d o m isati o n a n d 
bli n di n g  
As s u bjects o n tre at me nt wit h N N C 0 1 6 5-1 8 7 5 / pl ace b o 2. 0 m g 
nee d t o be cl osel y m o nit ore d f or s afet y a n d t oler a bilit y, t he 
r a n d o mis ati o n of t he 2. 0 m g d ose gr o u ps  will be restricte d t o 
1 -3  sites.
T o e ns ure safet y m o nit ori n g 
of s u bj ect s recei vi n g 2. 0 m g 
N N C 0 1 6 5 -1 8 7 5, 
ra n d o misati o n of s u bj ects 
f or t he 2. 0 m g ar ms will be 
restricte d t o 1-3 sites.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
Stat us:  
Fi n al  
P a ge:  
6  of 1 1 6  
Secti o n # a n d n a me  Descri pti o n  of c h a n ge  
Brief r ati o n ale  
Secti o n 6. 6  D ose 
m o dificati o n  
N ot a p plica ble f or t his trial . Please refer t o Secti o n 6. 1 f or 
descri pti o n of misse d d ose(s)  a n d f or g ui d a nce o n d ose 
re d ucti o n i n c ase t he s u bject d oes n ot t oler ate t he 
r a n do mise d t ar g et d ose . 
T he  refere nce t o Secti o n 6. 1 
has  bee n u p date d t o i ncl u de 
d ose re d ucti o ns i n case t he 
s u bj ect d oes n ot t olerate t he 
ra n d o mise d tar get d ose. 
Secti o n 7. 1  
Disc o nti n uati o n of 
trial treat me nt 
6 . A n u n acce pt a ble A E defi ne d as a n y se vere A E a n d/ or
seri o us A E ( S A E) j u d ge d as pr o b a bl y or p ossi bl y rel ate d t o
tri al pr o d uct b y t he i n vesti g at or
A ne w di sc o nti n uati o n 
criterio n  has bee n a d de d  f or 
c o nsi derati o n of safet y a n d 
t olera bilit y.  
Secti o n 8. 2. 4  
Electr ocar di o gra ms  
P art 2 o nl y:  
•
At visits w here P K s a m ples are c ollecte d t he E C G
rec o r di n gs m ust be perf or me d pri or t o P K s a m ple
c ollecti o n
T his was state d f or part 1, 
b ut is als o a p plica ble f or 
part 2.  
Secti o n 8. 2. 5. 1  Uri ne 
sa m ples 
Ne utr o p hil gelati nase -associ ate d  li p ocali n/cre ati ni ne 
T he na me of t he la b orat or y 
para meter ne utr o p hil 
gela ti nase-ass li p ocali n was 
u p date d t o ne utr o p hil 
gelati nase -ass ociate d 
li p ocali n/creati ni ne, beca use 
t hese res ults are re p orte d as 
a rati o. 
Secti o n 8. 8  
Bi o mar kers  
T he ass a ys use d f or S ol u ble Le pti n Rece pt o r a n d Le pti n are 
f or rese a rc h use o nl y, t hese res ults will be re p orte d directl y 
t o N o v o N or dis k. 
T he list of bi o mar kers was 
u p date d wit h b u llet i n de nts 
f or clarificati o n. 
It was a d de d t hat t he data 
f or s ol u ble le pti n rece pt or 
a n d le pti n will be re p orte d 
directl y t o N o v o N or dis k.  
Secti o n 9. 1  Statistical 
h y p ot heses  
P art 2  
F or t he pri mar y e n d p oi nt perce nta ge wei g ht c ha n ge fr o m 
ra n d o misati o n ( wee k 2 4  3 2 ) t o e n d-of -treat me nt ( wee k 4 0 4 8 ), 
t he s u peri orit y test f or N N C 0 1 6 5-1 8 7 5 1. 0 m g  a n d se ma gl uti de 
s.c. 2. 4 m g vers us place b o 1. 0 m g  a n d se ma gl uti de s.c. 2. 4 m g
will b e carrie d o ut as f oll o ws. As all s u bj ects will recei ve
se ma gl uti de s.c. 2. 4 m g a n d t o ease n otati o n, se ma gl uti de s.c. 2. 4
m g is i g n ore d i n t he n otati o n. Let μ
N N C 0 1 6 5 -1 8 7 5 , 1. 0 m g 2. 0 m g a n d
μ place b o , 1. 0 m g de n ote t he tr u e mea n of perce nta ge wei g ht c ha n ge
f or d ose le vel N N C 0 1 6 5-1 8 7 5 1. 0 m g  2. 0 m g  a n d t he place b o
1. 0 m g  gr o u p, res pecti vel y.
T e xt u p date d t o clarif y t hat 
efficac y e val uati o ns f or 
part  2 will be perf or me d 
usi n g t he p o p ulati o n of 
s u bj ects ra n d o mise d t o t he 
1. 0 m g d ose of N N C 0 1 6 5 -
1 8 7 5/ place b o.  
Secti o n 9. 2  Sa m ple 
size deter mi nati o n  
I n pr ot oc ol v ersi o n 4. 0, t he a d diti o n al r u n-i n visits ( V 9. 1 a n d 
V 9. 2) h a ve bee n acti v ate d, t his me a ns t h at t he s u bjects will 
be 8 w ee ks l o n ger o n se m a gl uti de 2. 4 m g bef ore 
r a n d o mis ati o n. H o w e ver, t his d oes n ot affect t he p o w er.  
Ne w te xt a d de d t o clarif y 
t hat t he acti vati o n of V 9. 1 
a n d V 9. 2 d oes n ot affect t he 
p o wer.  
Secti o n 9. 4. 3  
Sec o n dar y e n d p oi nt  
T E A Es a n d treat me nt e mer ge nt S A Es will be s u m marise d b y 
descri pti ve statistics f or b ot h 1. 0 m g N N C 0 1 6 5-1 8 7 5/ pl ace b o 
a n d 2. 0 m g N N C 0 1 6 5 -1 8 7 5/ pl ace b o . 
Safet y e val uati o n will b e 
d o ne f or b ot h 1. 0 m g a n d 
2. 0 m g d oses.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
Stat us:  
Fi n al  
P a ge:  
7  of 1 1 6  
Secti o n # a n d n a me  Descri pti o n  of c h a n ge  
Brief r ati o n ale  
Secti o n 9. 5  Data base 
l oc k 
Secti o n 9. 5 D at a b ase l oc k  
P art 1:  
D B L 1 of p art 1 will be perf or me d after L P L V ( w ee k 1 6). 
T he d at a i n sc o pe are p h ar m ac o ki netic a n d s afet y l a b d at a 
u ntil w ee k 1 6, w hic h will be use d f or t he i niti al s afet y 
c o m mittee decisi o n. After D B L 1, d at a will be u n bli n de d f or 
p art 1. U n bli n di n g after D B L 1 is n ot of a n y c o ncer n f or 
c o nti n ui n g p a rt 2, as sites a n d s u bjects are dissi mil ar f or p art 
1 a n d p art 2 of t he tri al.  
D B L 2 of p art 1 will be perf or me d after t he rest of t he d at a 
h as bee n c ollecte d. T he d at a i n sc o pe are p h ar m ac o ki neti c 
a n d s afet y l a b d at a ( u ntil w ee k 2 4) a n d a nti b o d y d at a.  
P art 2:  
D B L of p art 2 will be perf or me d after L P L V. After t he D B L 
h as bee n c o m plete d, t he d at a will be u n bli n de d f or p art 2.   
T o clarif y t hat u n bli n di n g of 
data fr o m part 1 at D B L 1 
c o ncer ns data fr o m part 1 
( u ntil wee k 1 6) o nl y. 
Secti o n 1 0. 2  
A p pe n di x 2: Cli nical 
la b orat or y tests 
A f o ot n ote h ave bee n a d de d t o A p pe n dix 2, T a ble  1 0 -1:  
1 Res ults o bt ai ne d usi n g ass a ys f or rese arc h use o nl y will be 
re p orte d directl y t o N o v o N or dis k.  
F o ot n otes h ave bee n a d de d t o A p pe n dix 2, T a ble  1 0 -2 :  
2 Res ults fr o m bi o m ar ker ass a ys rel ate d t o h u n ger a n d 
s atiet y, f or rese a rc h use o nl y, will be re p orte d directl y t o 
N o v o N or dis k.  
3 Res ults o bt ai ne d usi n g as s a y f or rese arc h use o nl y will be 
re p orte d directl y t o N o v o N or dis k.  
F urt her m ore, t he ass a ys use d f or gl uc a g o n, ne utr o p hil 
gel ati n ase -ass oci ate d li p oc ali n/cre ati ni ne, s ol u ble le pti n 
rece pt o r a n d le pti n are f or rese arc h use o nl y, he nce t hes e 
res ults will n ot be r e p orte d t o t he sites, b ut will be re p orte d 
directl y t o N o v o N or dis k.  
Ne utr o p hil gelati nase -ass ociat e d li p ocali n /cre ati ni ne 
T he f oll o wi n g la b orat or y 
assa ys are f or researc h use 
o nl y:  
•
Gl uca g o n
•
Ne utr o p hil gelati nase -
ass ociate d
li p ocali n/creati ni ne
•
S ol u ble le pti n rece pt or
•
le pti n
F or t hese 4 la b orat or y 
para meters, t he res ults are 
n ot distri b ute d t o sites b ut 
directl y t o N o v o N or dis k.  
I n T a ble 1-2, /cre ati ni ne 
was a d de d t o t he para meter 
na me, beca use t hese res ults 
are re p orte d as a rati o.  
Secti o n 1 0. 4  
A p pe n di x 4: 
C o ntrace pti ve 
g ui da nce a n d 
c ollecti o n of 
pre g na nc y 
i nf or mati o n 
I n de nts h ave bee n a d de d t o t he b ullet list wit h fe m ales n ot 
c o nsi dere d w o m a n of c hil d be ari n g p ote nti al ( W O C B P).  
T he b ullet list wit h 
cate g ories of fe males n ot 
c o nsi dere d W O C B P was 
missi n g se veral i n de nts. 
T his has bee n u p date d t o 
clarif y t he cate g ories.  
N o c ha n ges were ma d e t o 
t he c o nte nt of t he te xt. 
Secti o n 1 0. 8  
A p pe n di x 8: 
Rete nti o n of h u ma n 
bi osa m ples  
at V 1 0, V 1 4, V 1 4 c a n d V 1 8 
•
Ser u m a n d plas ma (f or a nal ys es of circ ulati n g bi o mar kers)
H u ma n bi osa m ples will als o 
be c ollecte d at t he ne w visit 
( V 1 4c). 
Secti o n 1 0. 9  
A p pe n di x 9: 
Miti gati o ns t o e ns ure 
s u bj ect safet y a n d 
data i nte grit y d uri n g 
e pi de mics/ pa n de mics 
(e. g. C O VI D-1 9)  
Visit 1 4 c has bee n a d de d t o 
fl owc hart of mi ni m u m 
assess me nts f or part 2 t o be 
perf or me d d uri n g l oc k d o w n  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
Stat us:  
Fi n al  
P a ge:  
8  of 1 1 6  
Secti o n # a n d n a me  Descri pti o n  of c h a n ge  
Brief r ati o n ale  
Secti o n 1 0. 1 1  
Pr ot oc ol a me n d me nt 
hist or y  
A p pe n di x 1 1: Pr ot oc ol a me n d me nt hist or y …  
T he pre vi o us a me n d me nt 
rati o nale a n d descri pti o n 
has bee n m o ve d t o 
A p pe n di x 1 1.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
9  of 1 1 6  
 
Ta ble of C o nte nts  
 
P a ge  
P r ot oc ol ame n d me nt  s u m m ar y of c h a n ges t a ble ........................................................................................... 2  
T a ble of C o nte nts .............................................................................................................................................. 9  
1  P r ot oc ol s u m m ar y  ..................................................................................................................................... 1 3  
1. 1  
S y n o psis  ............................................................................................................................................ 1 3  
1. 2  
Fl o wc hart  .......................................................................................................................................... 1 8  
2  I ntr o d ucti o n ............................................................................................................................................... 2 5  
2. 1  
Trial rati o nale  .................................................................................................................................... 2 5  
2. 2  
Bac k gr o u n d  ....................................................................................................................................... 2 6  
2. 2. 1  
Pe pti de Y Y ( N N C 0 1 6 5 -1 8 7 5)  ........................................................................................... 2 6  
2. 2. 2  
Gl uca g o n -li ke pe pti de-1 (se ma gl uti de)  ............................................................................. 2 6  
2. 2. 3  
Trial p o p ulati o n  ................................................................................................................. 2 6  
2. 3  
Be nefit -ris k assess me nt ..................................................................................................................... 2 7  
2. 4  
Ris k assess me nt  ................................................................................................................................ 2 8  
2. 4. 1  
Be nefit assess me nt  ............................................................................................................. 3 3  
2. 4. 2  
O verall be nefit -ris k c o ncl usi o n ......................................................................................... 3 3  
3  O bjecti ves a n d e n d p oi nts  .......................................................................................................................... 3 4  
3. 1  
Pri mar y, sec o n dar y a n d e x pl orat or y o bj ecti ves a n d esti ma n ds ......................................................... 3 4  
3. 2  
Pri mar y, sec o n dar y a n d e x pl orat or y e n d p oi nts  ................................................................................. 3 5  
3. 2. 1  
Pri mar y e n d p oi nt  ............................................................................................................... 3 5  
3. 2. 2  
Sec o n dar y e n d p oi nts  .......................................................................................................... 3 6  
3. 2. 2. 1  
C o nfir mat or y sec o n dar y e n d p oi nts  ................................................................ 3 6  
3. 2. 2. 2  
S u p p orti ve sec o n dar y e n d p oi nts  .................................................................... 3 6  
3. 2. 3  
E x pl orat or y e n d p oi nts ........................................................................................................ 3 7  
4  Tri al desi g n  ................................................................................................................................................ 3 8  
4. 1  
O verall desi g n  ................................................................................................................................... 3 8  
4. 2  
Scie nt ific rati o nale f or trial desi g n .................................................................................................... 4 1  
4. 2. 1  
S u bj ect i n p ut i nt o desi g n  ................................................................................................... 4 1  
4. 3  
J ustificati o n f or d ose ......................................................................................................................... 4 1  
4. 4  
E n d of trial defi niti o n  ........................................................................................................................ 4 2  
5  Tri al p o p ul ati o n  ......................................................................................................................................... 4 3  
5. 1  
I ncl usi o n criteria ............................................................................................................................... 4 3  
5. 2  
E xcl usi o n criteria  .............................................................................................................................. 4 3  
5. 3  
Lifest yle c o nsi derati o ns  .................................................................................................................... 4 4  
5. 3. 1  
Meals a n d dietar y restricti o ns  ............................................................................................ 4 4  
5. 3. 2  
Caffei ne, alc o h ol a n d t o bacc o  ........................................................................................... 4 5  
5. 3. 3  
P h ysical acti vit y  ................................................................................................................. 4 5  
5. 4  
Scree n fail ures  ................................................................................................................................... 4 5  
5. 5  
R u n -i n criteria a n d/ or ra n d o misati o n criteria .................................................................................... 4 5  
5. 5. 1  
R u n -i n criteria .................................................................................................................... 4 6  
5. 5. 2  
Ra n d o misati o n criteria  ....................................................................................................... 4 6  
5. 5. 3  
D osi n g da y criteria  ............................................................................................................ 4 6  
6  Tre at me nts  ................................................................................................................................................. 4 7  
6. 1  
Treat me nts a d mi nistere d  ................................................................................................................... 4 7  
6. 1. 1  
Me dical de vices  ................................................................................................................. 5 0  
6. 1. 1. 1  
I n vesti gati o nal me dical de vices ..................................................................... 5 0  
6. 1. 1. 2  
N o n -i n vesti gati o nal me dical de vices ............................................................. 5 0  
6. 2  
Pre parati o n/ ha n dli n g/st ora ge/acc o u nta bilit y  ..................................................................................... 5 1  
6. 3  
Meas ures t o mi ni mise bias: Ra n d o misati o n a n d bli n di n g ................................................................. 5 1  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 0  of 1 1 6  
 
6. 4  
Treat me nt c o m plia nce  ....................................................................................................................... 5 3  
6. 5  
C o nc o mita nt me dicati o n  ................................................................................................................... 5 3  
6. 6  
D ose m o dificati o n  ............................................................................................................................. 5 4  
6. 7  
Treat me nt after e n d of trial  ............................................................................................................... 5 4  
7  Disc o nti n u ati o n of tri al tre at me nt a n d s u bject disc o nti n u ati o n/ wit h dr a w al  ....................................... 5 5  
7. 1  
Disc o nti n uati o n of trial treat me nt  ..................................................................................................... 5 5  
7. 1. 1  
T e m p orar y disc o nti n uati o n of trial treat me nt  .................................................................... 5 6  
7. 2  
S u bj ect disc o nti n uati o n/ wit h dra wal fr o m t he trial  ............................................................................ 5 6  
7. 2. 1  
Re place me nt of s u bjects  .................................................................................................... 5 7  
7. 3  
L ost t o f oll o w -u p ............................................................................................................................... 5 7  
8  Tri al assess me nts a n d pr oce d ures ............................................................................................................ 5 8  
8. 1  
Efficac y assess me nts  ......................................................................................................................... 5 9  
8. 1. 1  
B o d y meas ure me nts  ........................................................................................................... 5 9  
8. 1. 2  
Cli nical efficac y la b orat or y assess me nts  ........................................................................... 5 9  
8. 2  
Safet y assess me nts  ............................................................................................................................ 6 0  
8. 2. 1  
Me ntal Healt h i nstr u me nts ................................................................................................. 6 0  
8. 2. 2  
P h ysical e xa mi nati o ns  ....................................................................................................... 6 1  
8. 2. 3  
Vital si g ns  .......................................................................................................................... 6 1  
8. 2. 4  
Electr ocar di o gra ms  ............................................................................................................ 6 2  
8. 2. 5  
Cli nical safet y la b orat or y assess me nts  .............................................................................. 6 2  
8. 2. 5. 1  
Uri ne sa m ples  ................................................................................................. 6 2  
8. 2. 6  
I nj ecti o n site reacti o ns ....................................................................................................... 6 3  
8. 3  
A d verse e ve nts a n d seri o us a d verse e ve nts  ....................................................................................... 6 3  
8. 3. 1  
Ti me peri o d a n d fre q ue nc y f or c ollecti n g A E a n d S A E i nf or mati o n  ................................ 6 4  
8. 3. 2  
Met h o d of detecti n g A Es a n d S A Es  .................................................................................. 6 4  
8. 3. 3  
F oll o w -u p of A Es a n d S A Es  ............................................................................................. 6 4  
8. 3. 4  
Re g ulat or y re p orti n g re q uire me nts f or S A Es  .................................................................... 6 5  
8. 3. 5  
Pre g na nc y  .......................................................................................................................... 6 5  
8. 3. 6  
T ec h ni cal c o m plai nts ......................................................................................................... 6 5  
8. 4  
Treat me nt of o ver d ose  ...................................................................................................................... 6 5  
8. 5  
P har mac o ki netics  .............................................................................................................................. 6 6  
8. 6  
P har mac o d y na mics  ........................................................................................................................... 6 6  
8. 7  
Ge netics  ............................................................................................................................................ 6 7  
8. 8  
Bi o mar kers  ........................................................................................................................................ 6 7  
8. 9  
Bi osa m ples f or f ut ure researc h  ......................................................................................................... 6 7  
8. 1 0  I m m u n o ge nicit y assess me nts ............................................................................................................ 6 8  
9  St atistic al c o nsi der ati o ns  .......................................................................................................................... 6 9  
9. 1  
Statistical h y p ot heses  ........................................................................................................................ 6 9  
9. 2  
Sa m ple size deter mi nati o n  ................................................................................................................ 6 9  
9. 3  
P o p ulati o ns f or a nal yses  ................................................................................................................... 7 1  
9. 4  
Statistical a nal yses  ............................................................................................................................ 7 2  
9. 4. 1  
Ge neral c o nsi derati o ns  ...................................................................................................... 7 2  
9. 4. 2  
Pri mar y e n d p oi nt  ............................................................................................................... 7 3  
9. 4. 3  
Sec o n dar y e n d p oi nt  ........................................................................................................... 7 4  
9. 4. 3. 1  
C o nfir mat or y sec o n dar y e n d p oi nts  ................................................................ 7 4  
9. 4. 3. 2  
S u p p orti ve sec o n dar y e n d p oi nts  .................................................................... 7 4  
9. 4. 4  
E x pl orat or y e n d p oi nt  ......................................................................................................... 7 5  
9. 4. 5  
Ot her safet y a nal yses  ......................................................................................................... 7 5  
9. 4. 6  
Ot her a nal yses  ................................................................................................................... 7 6  
9. 4. 6. 1  
P har mac o ki netic  a n d/ or p har mac o d y na mic m o delli n g  .................................. 7 6  
9. 5  
Data base l oc k  .................................................................................................................................... 7 6  
9. 6  
I nterim a nal yses  ................................................................................................................................ 7 6  
9. 7  
Data m o nit ori n g c o m mittee  .............................................................................................................. 7 6  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 1  of 1 1 6  
 
9. 8  
Re p orti n g of t he mai n part of t he trial  ............................................................................................... 7 6  
1 0  S u p p orti n g d oc u me nt ati o n a n d o per ati o n al c o nsi der ati o ns .................................................................. 7 7  
1 0. 1  A p pe n di x 1: Re g ulat or y, et hical, a n d trial o versi g ht c o nsi derati o ns  ................................................ 7 7  
1 0. 1. 1  
Re g ulat or y a n d et hical c o nsi derati o ns  ............................................................................... 7 7  
1 0. 1. 2  
Fi na ncial discl os ure  ........................................................................................................... 7 7  
1 0. 1. 3  
I nf or me d c o nse nt pr ocess .................................................................................................. 7 7  
1 0. 1. 4  
I nf or mati o n t o s u bj ects d uri n g trial ................................................................................... 7 8  
1 0. 1. 5  
Data pr otecti o n  .................................................................................................................. 7 8  
1 0. 1. 6  
C o m mittees str uct ure  ......................................................................................................... 7 9  
1 0. 1. 6. 1  
N o v o N or dis k safet y c o m mittee ..................................................................... 7 9  
1 0. 1. 6. 2  
I nter nal N o v o N or dis k safet y o versi g ht gr o u p ............................................... 7 9  
1 0. 1. 6. 3  
Data m o nit ori n g c o m mittee ............................................................................ 7 9  
1 0. 1. 6. 4  
E ve nt a dj u dicati o n c o m mittee  ........................................................................ 7 9  
1 0. 1. 7  
Disse mi nati o n of cli nical trial data  .................................................................................... 7 9  
1 0. 1. 8  
Data q ualit y ass ura nce  ....................................................................................................... 7 9  
1 0. 1. 8. 1  
Case re p ort f or ms  ........................................................................................... 7 9  
1 0. 1. 8. 2  
M o nit ori n g  ..................................................................................................... 8 0  
1 0. 1. 8. 3  
Pr ot oc ol c o m plia nce  ....................................................................................... 8 0  
1 0. 1. 9  
S o urce d oc u me nts  .............................................................................................................. 8 1  
1 0. 1. 1 0  Rete nti o n of cli nical trial d oc u me ntati o n  .......................................................................... 8 1  
1 0. 1. 1 1  Trial a n d site cl os ure .......................................................................................................... 8 1  
1 0. 1. 1 2  Res p o nsi bilities  .................................................................................................................. 8 2  
1 0. 1 . 1 3 I n de m nit y state me nt .......................................................................................................... 8 3  
1 0. 1. 1 4  P u blicati o n p olic y  .............................................................................................................. 8 3  
1 0. 1. 1 4. 1  
C o m m u nicati o n of res ults  .............................................................................. 8 3  
1 0. 1. 1 4. 2  
A ut h ors hi p  ...................................................................................................... 8 4  
1 0. 1. 1 4. 3  
Sit e -s pecific p u blicati o n(s) b y i n vesti gat or(s)................................................ 8 4  
1 0. 1. 1 4. 4  
I n vesti gat or access t o data a n d re vie w of res ults ........................................... 8 4  
1 0. 2  A p pe n di x 2: Cli nical la b orat or y tests ................................................................................................ 8 5  
1 0. 3  A p pe n di x 3: A d verse e ve nts: Defi niti o ns a n d pr oce d ures f or rec or di n g, e val uati o n, f oll o w -u p, 
a n d re p orti n g ..................................................................................................................................... 8 8  
1 0. 3. 1  
Defi niti o n of A E  ................................................................................................................ 8 8  
1 0. 3. 2  
Defi niti o n of a n S A E  ......................................................................................................... 8 8  
1 0. 3. 3  
Descri pti o n of A Es re q uiri n g a d diti o nal data c ollecti o n  ................................................... 8 9  
1 0. 3. 4  
Rec or di n g a n d f oll o w -u p of A E a n d/ or S A E  ..................................................................... 9 1  
1 0 . 3. 5 
Re p orti n g of S A Es  ............................................................................................................. 9 3  
1 0. 4  A p pe n di x 4: C o ntrace pti ve g ui da nce a n d c ollecti o n of pre g na nc y i nf or mati o n  ............................... 9 5  
1 0. 5  A p pe n di x 5: Tec h nical c o m plai nts: Defi niti o n a n d pr oce d ures f or rec or di n g, e val uati o n, 
f oll o w-u p a n d re p orti n g  .................................................................................................................... 9 8  
1 0. 5. 1  
Defi niti o n of tec h nical c o m plai nt  ...................................................................................... 9 8  
1 0. 5. 2  
Rec or di n g a n d f oll o w -u p of tec h nical c o m plai nts  ............................................................. 9 8  
1 0. 5. 3  
Re p orti n g of tec h nical c o m plai nts  ..................................................................................... 9 9  
1 0. 6  A p pe n di x 6: Ge netics  ...................................................................................................................... 1 0 0  
1 0. 7  A p pe n di x 7: Me dical de vice a d verse e ve nts, a d verse de vice effects, seri o us a d verse e ve nts 
a n d de vice deficie ncies: Defi niti o n a n d pr oce d ures f or rec or di n g, e val uati n g, f oll o w-u p, a n d 
re p orti n g .......................................................................................................................................... 1 0 1  
1 0. 7. 1  
Defi niti o n of A E a n d a d verse de vice effects ( A D E)  ....................................................... 1 0 1  
1 0. 7. 2  
Defi niti o n of S A E, seri o us a d verse de vice effect ( S A D E) a n d u ne xce pte d seri o us 
a d verse de vice effect ( U S A D E)  ...................................................................................... 1 0 1  
1 0. 7. 3  
Defi niti o n of de vice deficie nc y  ....................................................................................... 1 0 2  
1 0. 7. 4  
Rec or di n g a n d f oll o w -u p of A E a n d/ or S A E a n d de vice deficie ncies  ............................ 1 0 2  
1 0. 7. 5  
Re p orti n g of S A Es  ........................................................................................................... 1 0 3  
1 0. 7. 6  
Re p orti n g of de vice deficie ncies  ..................................................................................... 1 0 3  
1 0. 8  A p pe n di x 8: Rete nti o n of h u ma n bi osa m ples  ................................................................................. 1 0 4  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 2  of 1 1 6  
 
1 0. 9  A p pe n di x 9: Miti gati o ns t o e ns ure s u bject safet y a n d data i nte grit y d uri n g 
e pi de mics/ pa n de mics (e. g. C O VI D -1 9)  .......................................................................................... 1 0 6  
1 0. 9. 1  
Visits  ................................................................................................................................ 1 0 6  
1 0. 9. 2  
Assess m e nts ..................................................................................................................... 1 0 6  
1 0. 9. 3  
Trial pr o d uct  .................................................................................................................... 1 0 7  
1 0. 9. 3. 1  
Alter nati ve dis pe nsi n g met h o ds  ................................................................... 1 0 7  
1 0. 9. 4  
Mi ni m u m assess me nts f or Part 2 t o be perf or me d d uri n g  l oc k d o w n .............................. 1 0 7  
1 0. 1 0  A p pe n di x 1 0: A b bre viati o ns  ........................................................................................................... 1 0 9  
1 0. 1 1  A p pe n di x 1 1: Pr ot oc ol a me n d me nt hist or y  .................................................................................... 1 1 1  
1 1  Ref ere nces  ................................................................................................................................................ 1 1 3  
 
Attac h me nt I Gl o bal list of ke y staff a n d rel e va nt de part me nts a n d s u p pliers 
Attac h me nt II C o u ntr y list of ke y st aff a n d rele va nt de part me nts  
 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 3  of 1 1 6  
 
1  Pr ot oc ol s u m m ar y  
1. 1  
S y n o psis  
R ati o n ale:  
T he prese nt tri al is desi g ne d t o i n vesti gate effi cac y a n d s afet y of N N C 0 1 6 5 -1 8 7 5 s u bc uta ne o us 
(s.c.) o nce wee kl y as a n a d d o n t o se ma gl uti de s.c. 2. 4 m g o nce  wee kl y c o m pare d t o c o nti n ui n g 
se ma gl uti de s. c. 2. 4 m g o nce wee kl y al o ne f or wei g ht ma na ge me nt i n s u bjects wit h o besit y. T he 
trial c o nsists of t w o parts, Part 1 a n d Part 2. I n Part 1, safet y a n d t olera bilit y will be ass esse d d uri n g 
c o-escalati o n of N N C 0 1 6 5 -1 8 7 5 a n d se ma gl uti de. I n Part 2, N N C 0 1 6 5 -1 8 7 5 will be a d de d o n t o 
se ma gl uti de s. c. 2. 4 m g at stea d y stat e t o c o m pare t he efficac y a n d safet y of N N C 0 1 6 5 -1 8 7 5 a d de d 
o n t o se ma gl uti de s.c. 2. 4 m g vers us c o nti n ui n g se ma gl uti de s.c. 2. 4 m g al o ne. T he i nitial r u n -i n 
peri o d i n Part 2 of t he tri al ( Part 2a) all o ws f or wei g ht l oss t o be o btai ne d wit h se ma gl uti de s.c. 
2. 4  m g bef ore t he a d diti o n of N N C 0 1 6 5 -1 8 7 5 ( Part 2 b), t h us all o wi n g f or wei g ht l oss o btai ne d b y 
t his a d diti o n t o be c o m pare d wit h t he wei g ht l oss o btai ne d wit h c o nti n ui n g se ma gl uti de s. c. 2. 4 m g 
o nl y. T his trial will pr o vi de pr o of of pri nci ple t o g ui de f urt her  cli nical de vel o p me nt.  
O bjecti ves a n d e n d p oi nts:  
P art 1  
Pri m ar y o bjecti ve  
T o e val uate t he s afet y a n d t olera bilit y of c o -es calati o n of o nce -wee kl y d oses of N N C 0 1 6 5 -1 8 7 5 a n d 
se ma gl uti de s. c. 2. 4 m g a d mi nistere d si m ulta ne o usl y as se parat e d oses i n s u bjects wi t h o besit y. 
P art 2  
Pri m ar y o bjecti ve  
T o c o m pare t h e effect of N N C 0 1 6 5 -1 8 7 5 1. 0 m g a d de d o n t o se ma gl uti de s.c. 2. 4 m g at stea d y state 
vers us c o nti n ui n g s e ma gl uti de s.c. 2. 4 m g al o n e o n b o d y wei g ht i n s u bjects wit h o besit y.  
Sec o n d ar y o bjecti ve  
T o c o m pare t h e effect of N N C 0 1 6 5 -1 8 7 5 1. 0 m g a d de d o n t o se ma gl uti de s.c. 2. 4 m g at stea d y state 
vers us c o nti n ui n g s e ma gl uti de s.c. 2. 4 m g al o n e i n s u bjects wit h o besit y o n:  
•  Gl ycae mic c o ntr ol  
•  Waist circ u mfere n ce  
•  Car di o vasc ular ris k fact ors  
T o c o m pare t h e safet y a n d t o lera bilit y of N N C 0 1 6 5-1 8 7 5  1. 0 m g a n d N N C 0 1 6 5 -1 8 7 5 2. 0 m g  a d de d 
o n t o se ma gl uti de s.c. 2. 4  m g vers us c o nti n ui n g se ma gl uti de s.c. 2. 4 m g al o ne i n s u bjects wit h 
o besit y.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 4  of 1 1 6  
 
Pri m ar y e n d p oi nt  
P art 1  
E n d p oi nt title  
Ti me fr a me  
U nit  
N u m ber of treat me nt -e mer ge nt 
a d verse e ve nts ( T E A Es)  
Fr o m ti me of d osi n g ( da y 1) t o 
f oll o w-u p ( wee k 2 4)  
N u m ber of e ve nts  
P art 2  
E n d p oi nt title  
Ti me fr a me  
U nit  
C ha n ge i n b o d y wei g ht  
Fr o m ra n d o misati o n ( wee k 3 2 ) t o 
e n d of treat me nt ( wee k 4 8 ) 
P erce nta ge  
Esti m a n ds  
Esti ma n ds a p pl y f or st atistical a nal ysis of Part 2. 
Pri m ar y esti m a n d  
T he esti ma n d will q ua ntif y t he a vera ge tr eat me nt of N N C 0 1 6 5 -1 8 7 5  1. 0 m g  as a n a d d o n t o 
se ma gl uti de s. c. 2. 4 m g relati ve t o place b o  1. 0 m g  as a n a d d o n t o se ma gl uti de s.c. 2. 4 m g 
re gar dl ess of treat me nt disc o nti n uati o n a n d resc u e i nter ve nti o ns (a nti-o besit y dr u gs or de vices or 
bariatric s ur ger y) wit h res pect t o relati ve c ha n ge i n b o d y wei g ht fr o m wee k 3 2  t o wee k 4 8 . T he 
s u bject p o p ulati o n is all s u bjects ra n d o mise d t o 1. 0 m g  N N C 0 1 6 5 -1 8 7 5/ place b o,  w h o are a bl e t o 
reac h t h e tar get d ose of s e ma gl uti de 2. 4 m g d uri n g 3 2  wee ks of r u n -i n wit h escalati n g se ma gl uti de 
d oses.  
A d diti o n al esti m a n d  
T he esti ma n d will q ua ntif y t he a vera ge tr eat me nt of N N C 0 1 6 5 -1 8 7 5 1. 0 m g as a n a d d o n t o 
se ma gl uti de s. c. 2. 4 m g relati ve t o place b o 1. 0 m g as a n a d d o n t o se ma gl uti de s.c. 2. 4 m g i n all 
s u bjects w h o re mai n o n ra n d o mise d treat me nt f or t he e ntire pla n ne d d urati o n of t he treat me nt 
peri o d a n d d o n ot start a n y resc ue i nter ve nti o n (a nti -o besit y dr u gs or de vices or bariatric s ur ger y) 
wit h res pect t o rel ati ve c ha n ge i n b o d y wei g ht fr o m wee k 3 2  t o wee k 4 8 . T he s u bject p o p ulati o n is 
all s u bjects ra n d o mise d t o 1. 0 m g N N C 0 1 6 5 -1 8 7 5/ place b o , w h o are a bl e t o reac h t h e tar get d ose of 
se ma gl uti de 2. 4 m g d uri n g 3 2  w ee ks of r u n -i n wit h escalati n g se ma gl uti de d oses. 
Attri b ute  
 
Tre at me nt  
N N C 0 1 6 5 -1 8 7 5 as a n a d d o n t o se ma gl uti de s.c. 2. 4 m g vers us c o nti n ui n g o n 
place b o as a n a d d o n t o se ma gl uti de s.c. 2. 4 m g  
P o p ul ati o n  
All s u bj ects  ra n d o mise d t o 1. 0 m g N N C 0 1 6 5 -1 8 7 5/ place b o f or w h o m se ma gl uti de 
ha s bee n escalate d t o t he tar get d ose wit h se ma gl uti de 2. 4 m g at wee k 2 8  a n d at 
tar get d ose at t he ra n d o misati o n visit ( wee k 3 2 ) 
E n d p oi nt  
P erce nt c ha n ge i n b o d y wei g ht fr o m wee k 3 2  t o wee k 4 8  
I nterc urre nt e v e nts 
Treat me nt disc o nti n uati o n: tre at me nt p olic y strate g y  
Resc ue i nter ve nti o ns (a nti -o besit y dr u gs or de vices or bariatric s ur ger y): treat me nt 
p olic y/effecti ve ness p olic y str ate g y 
P o p ul ati o n -le vel s u m m ar y 
Differe nce i n a vera ge perce nt c ha n ge i n b o d y wei g ht bet wee n N N C 0 1 6 5 -1 8 7 5  
1. 0  m g  as a n a d d o n t o se ma gl uti de s.c. 2. 4 m g vs. place b o 1. 0 m g as a n a d d o n t o 
se ma gl uti de s.c. 2. 4 m g  
  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 5  of 1 1 6  
 
 
O ver all desi g n:  
P art 1  
Part 1 is a 1 6 -wee k, f o ur -ar me d, d o u ble -bli n de d ( wit hi n ar ms), ra n d o mise d, place b o -c o ntr olle d  
si n gle-site trial c o m pari n g c o-escalati o n of t w o d oses of N N C 0 1 6 5 -1 8 7 5 as a n a d d o n t o 
se ma gl uti de s. c. 2. 4 m g v ers us place b o a d de d o n t o se ma gl uti de s. c. 2. 4 m g i n s u bjects wit h o besit y. 
I n t otal, 2 4 s u bje cts will be ra n d o mise d 2: 1: 2: 1 t o recei v e N N C 0 1 6 5-1 8 7 5 1. 0 m g/ N N C 0 1 6 5 -1 8 7 5 
place b o or N N C 0 1 6 5 -1 8 7 5 2. 0 m g/ N N C 0 1 6 5 -1 8 7 5 place b o. All s u bjects will recei ve s e ma gl uti de 
2. 4 m g. T he f oll o w -u p peri o d is 8 wee ks ( please see Fi g ure  4 -1 ). 
P art 2  
Part 2 is a 4 8 -wee k, f o ur-ar me d, d o u ble -bli n de d ( wit hi n ar ms), ra n d o mise d, place b o -c o ntr olle d, 
m ulti -ce ntre, pr o of -of -pri nci ple trial c o m pari n g o n ce wee kl y N N C 0 1 6 5 -1 8 7 5 as a d d o n t o o nce -
wee kl y se ma gl uti de s.c. 2. 4 m g vers us place b o as a d d o n t o o nce wee kl y s e ma gl uti de s.c. 2. 4 m g i n 
s u bjects wit h o besit y. I n t otal, 9 0 s u bjects are pla n ne d t o be e nr olle d i n Part 2a t o e ns ure 
a p pr o xi matel y 7 5 s u bjects eli gi ble f or ra n d o misati o n i n Part 2 b. T he f oll o w -u p peri o d is 8  wee ks.   
I n p art 2 b, 1 2  s u bjects will be ra n d o mise d 2: 1 t o t he 2. 0 m g N N C 0 1 6 5 -1 8 7 5/ place b o  ar ms f or safet y 
e val uati o n of t he 2. 0 m g d ose. T he re m ai ni n g s u bj ects will be ra n d o mise d 2: 1 t o t he 1. 0  m g 
N N C 0 1 6 5 -1 8 7 5/ place b o  ar ms f or e v al uati o n of efficac y a n d s afet y of N N C 0 1 6 5-1 8 7 5.  
Ke y i ncl usi o n criteri a  
S u bjects are eli gi ble t o b e i ncl u de d i n t he trial o nl y if all of t h e f oll o wi n g criteria a p pl y : 
•  I nf or me d c o ns e nt o btai ne d bef ore a n y trial-relate d acti vities. Trial-rel ate d acti vities are a n y 
pr oce d ures t hat are carrie d o ut as part of t he trial, i ncl u di n g acti vities t o deter mi ne s uita bilit y f or 
t he trial. 
•  Male or fe m ale, a ge a b o v e or e q ual t o 1 8 ye ars at t he ti me of si g ni n g i nf or m e d c o nse nt.  
•  B o d y Mass I n d e x ( B MI) 3 0. 0 –  4 5. 0 k g/ m 2 ( b ot h i ncl usi ve) at t he scree ni n g visit. 
Ke y e xcl usi o n criteri a  
•  H b A 1 c ≥ 4 8 m m ol/ m ol ( 6. 5 %) as meas ure d b y a ce ntral la b orat or y at scree ni n g.  
•  Hist or y of t y p e 1 or t y pe 2 di a betes mellit us.  
Attri b ute  
 
Tre at me nt  
N N C 0 1 6 5 -1 8 7 5 as a n a d d o n t o se ma gl uti de s.c. 2. 4 m g vers us c o nti n ui n g place b o 
as a n a d d o n t o se ma gl uti de s. c. 2. 4 m g  
P o p ul ati o n  
All s u bj ects ra n d o mise d t o 1. 0 m g N N C 0 1 6 5 -1 8 7 5/ place b o f or w h o m se ma gl uti de 
ha s bee n escalate d t o t he tar get d ose wit h se ma gl uti de 2. 4 m g at wee k 2 8  a n d at 
tar get d ose at t he ra n d o misati o n visit ( wee k 3 2 ) 
E n d p oi nt  
Relati ve c ha n ge i n b o d y wei g ht fr o m wee k 3 2  t o wee k 4 8  
I nterc urre nt e v e nts 
Treat me nt disc o nti n uati o n: h y p ot hetical strate g y  
Resc ue i nter ve nti o ns (a nti -o besit y dr u gs or de vices or bariatric  s ur ger y): 
h y p ot hetical/efficac y strate g y  
P o p ul ati o n -le vel s u m m ar y 
Differe nce i n a vera ge perce nt c ha n ge i n b o d y wei g ht bet wee n N N C 0 1 6 5 -1 8 7 5 
1. 0  m g as a n a d d o n t o se ma gl uti de s.c. 2. 4 m g vs. place b o as a n a d d o n t o 
se ma gl uti de s.c. 2. 4 m g  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
1 5
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 6  of 1 1 6  
 
N u m ber of s u bjects:  
P art 1  
A p pr o xi matel y 7 5  s u bj ects will be scree ne d t o ac hie ve 2 4 s u bjects ra n d o ml y assi g ne d t o trial 
pr o d uct.  
P art 2  
Base d o n N N 9 5 3 6 -4 3 7 6 it is e x pecte d t hat 1 7 % s u bjects will dr o p o ut bef ore ra n d o misati o n i n 
wee k  3 2  or n ot b e a ble t o meet t he eli gi bilit y criteria at wee k 3 2 . T o acc o u nt f or t his, it is pla n ne d t o 
all o w a p pr o xi matel y 9 0 patie nts t o e nter (treat me nt or r u n -i n peri o d) at Visit 2 t o e ns ure t hat 7 5 
s u bjects are ra n d o mize d at wee k 3 2 . F urt her, a p pr o xi matel y 1 0 6 s u bjects will be scree n e d t o e ns ure 
a p pr o xi matel y 9 0 eli gi ble s u bjects (c o m plete Visit 2 or s uccessf ull y e nter r u n -i n peri o d). 
Tre at me nt gr o u ps a n d d ur ati o n:  
P art 1  
T he t otal trial d urati o n f or t he i n di vi d ual s u bject will be a p pr o xi matel y 2 6 wee ks. T he tri al i ncl u des 
a scree ni n g peri o d of a p pr o xi matel y 2 wee ks. Eli gi ble s u bjects f ulfilli n g all ra n d o misati o n criteria at 
visit 2 will be ra n d o mise d i n a 2: 1: 2: 1 ma n ner t o recei ve t ar get d oses of N N C 0 1 6 5 -1 8 7 5 1. 0 m g, 
N N C 0 1 6 5 -1 8 7 5 1. 0 m g place b o, N N C 0 1 6 5 -1 8 7 5 2. 0 m g or N N C 0 1 6 5 -1 8 7 5 2. 0 m g place b o. All 
s u bjects will recei ve s e m a gl uti de s.c. 2. 4 m g. T h e starti n g d ose of se ma gl uti de is 0. 2 5 m g i n all 
ar ms. T he starti n g d ose of N N C 0 1 6 5 -1 8 7 5 is 0. 0 5 m g or 0. 1 m g, de p e n di n g o n treat me nt ar m 
( please see Fi g ure  4 -1 ). T he treat me nt c o nti n ues u ntil t he ‘e n d of treat me nt’ visit f oll o we d b y a n 
8 -wee k f oll o w -u p peri o d.  
P art 2  
T he t otal trial d urati o n f or t he i n di vi d ual s u bject will be a p pr o xi matel y 5 8  wee ks. Part 2 c o nsists of  
a scree ni n g peri o d of a p pr o xi matel y 2 wee ks f oll o we d b y t w o treat me nt parts : a 3 2 -wee k o p e n -la bel 
r u n-i n part wit h d ose es calati o n of se ma gl uti de al o ne (Part 2a), a n d a 1 6 -wee k sec o n d p art ( Part 2 b), 
w here N N C 0 1 6 5 -1 8 7 5 or N N C 0 1 6 5 -1 8 7 5 place b o is a d de d t o se ma gl uti de s.c. 2. 4 m g. I n Part 2a, 
all s u bjects will recei ve s e ma gl uti de wit h d ose escalati o n e ver y 2 wee ks f or 8 wee ks fr o m 0. 2 5 m g 
se ma gl uti de t o t he tar get d ose of 2. 4 m g . At visit 1 0 , t he s u bjects e nter Part 2 b; i n a d diti o n t o 
recei vi n g se m a gl uti de s.c. 2. 4 m g, eli gi ble s u bjects f ulfilli n g all ra n d o misati o n criteria will be 
ra n d o mise d as f oll o w s: 1 2 s u bjects will be ra n d o mise d 2: 1 t o recei ve N N C 0 1 6 5 -1 8 7 5 2. 0  m g or 
place b o 2. 0  m g a n d t he re m i n der of s u bjects will be ra n d o mise d  ( 2: 1) t o r ecei ve N N C 0 1 6 5-1 8 7 5 
1 . 0 m g or pla ce b o 1 . 0 m g.  T he starti n g d os e of N N C 0 1 6 5 -1 8 7 5 is 0. 0 5  m g a n d d ose escal ati o n wit h 
N N C 0 1 6 5 -1 8 7 5 or place b o will be perf or me d e ver y s ec o n d wee k t o reac h t he mai nte na nce d ose of 
1 . 0 m g or 2. 0 m g . T he tr eat me nt c o nti n ues u ntil t he ‘e n d of tr eat me nt’ visit f oll o we d b y a n 8-wee k 
f oll o w-u p peri o d.  
T he f oll o wi n g tri al pr o d u cts will be s u p plie d b y N o v o N or dis k f or t he d urati o n of t he trial:  
•  N N C 0 1 6 5 -1 8 7 5 A 0. 2  m g/ m L/ P la ce b o A, 3 m L cartri d ge f or use i n N o v o P e n® 4 ( d ura ble 
de vice)  
•  N N C 0 1 6 5 -1 8 7 5 A 5. 0  m g/ m L/ Pla ce b o A, 3 m L cartri d ge f or use i n N o v o P e n ® 4 ( d ura ble 
de vice)  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
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1
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 of
  Pr ot oc ol  versi o n 4. 0
1 6
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 7  of 1 1 6  
 
•  Se ma gl uti de B 3. 0 m g/ m L 3 m L P D S 2 9 0 pre -fille d pe n-i nject or 
D at a m o nit ori n g c o m mittee:  
N ot a p plica ble i n  t his trial. 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
1 7
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
      
Date:  
0 5 A pril 2 0 2 2  
Stat us:  
Fi n al  
N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
      
V ersi o n:  
4. 0  
P a ge:  
1 8  of 1 1 6  
 
1. 2  
Fl o w c h art  
P art 1  
 
 
Pr ot oc ol  
Secti o ns  
Scree ni n g  
R a n d o mis ati o n  
P Y Y a n d Se m a d ose es c al ati o n a n d m ai nte n a nce peri o d  
E n d of tre at me nt  
P ost tre at me nt  
E n d of tri al  
 Visit  
 
V 1  
V 2  
V 3  
V 4  
V 5  
V 6  
V 7  
V 8  
V 9  
V 1 0  
V 1 1  
V 1 2  
V 1 3  
V 1 4  
V 1 5  
V 1 6  
V 1 7  
Ti mi n g i n Wee ks ( W)  
 
-1  
0  
2  
4  
6  
8  
1 0  
1 2  
1 4  
1 6  
1 8  
2 4  
 Ti mi n g of Visit ( Da ys)  
 
-7  
1  
4 *  
1 5  
1 8 *  
2 9  
3 2 *  
4 3  
5 7  
6 0 *  
7 1  
8 5  
8 8 *  
9 9  
1 1 3  
1 2 7  
1 6 9  
 Visit Wi n d o w ( Da ys)  
 
-7/ 0  
± 0  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
0/ 5  
    Atte n d Visit Fasti n g  
5. 3. 1  
 
X  
 
 
 
 
 
 
X  
 
 
 
 
 
X  
 
X  
    I nf or me d C o nse nt a n d De m o gr a p h ya  
1 0. 1. 3  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Eli gi bilit y Criteria  
5. 1 ,5. 2  
X  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Ra n d o misati o n Criteria a n d Ra n d o misati o n  
7. 1  
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Disc o nti n uati o n Criteria  
7. 1  
 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
 
 
    C o nc o mita nt Me dicati o n  
6. 5  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
    Me dical Hist or y/ C o nc o mita nt Ill ness  
8. 2  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Wei g ht Hist or y  
8. 2  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Ris k Fact ors  
8. 2  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    T o bacc o Use c 
8. 2  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    C hil d beari n g P ote ntial  
1 0. 4  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Hi g hl y se nsiti ve u ri n e p re g na nc y Testb  
1 0. 4  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
    B o d y Meas ure me nts  
8. 1. 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       Hei g ht  
8. 1. 1  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       B o d y Wei g ht  
8. 1. 1  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
       B MI  
8. 1. 1  
X  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       Waist Circ u mfere nc e  
8. 1 . 1 
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
X  
 
 
    P h ysical E x a mi n ati o n  
8. 2. 2  
X  
 
 
 
 
X  
 
 
X  
 
 
X  
 
 
X  
X  
X  
    A d verse E ve nt  
8. 3 ,1 0. 3  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
    A E Re q uiri n g A d diti o nal Data  
1 0. 3. 3  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       Ac ute Gall bla d der Disease  
1 0. 3. 3  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
       Ac ute P a ncreatitis  
1 0. 3. 3  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
       Ac ute Ki d ne y I nj ur y  
1 0. 3. 3  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
 .
-
 |
1
V V- T M F- 5 0 4 2 3 4 5
  Pr ot oc ol  versi o n 4. 0
 |
1 8
 of
1 1 6

Pr ot o c ol  
      
Date:  
0 5 A pril 2 0 2 2  
Stat us:  
Fi n al  
N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
      
V ersi o n:  
4. 0  
P a ge:  
1 9  of 1 1 6  
 
 
 
Pr ot oc ol  
Secti o ns  
Scree ni n g  
R a n d o mis ati o n  
P Y Y a n d Se m a d ose es c al ati o n a n d m ai nte n a nce peri o d  
E n d of tre at me nt  
P ost tre at me nt  
E n d of tri al  
 Visit  
 
V 1  
V 2  
V 3  
V 4  
V 5  
V 6  
V 7  
V 8  
V 9  
V 1 0  
V 1 1  
V 1 2  
V 1 3  
V 1 4  
V 1 5  
V 1 6  
V 1 7  
Ti mi n g i n Wee ks ( W)  
 
-1  
0  
2  
4  
6  
8  
1 0  
1 2  
1 4  
1 6  
1 8  
2 4  
 Ti mi n g of Visit ( Da ys)  
 
-7  
1  
4 *  
1 5  
1 8 *  
2 9  
3 2 *  
4 3  
5 7  
6 0 *  
7 1  
8 5  
8 8 *  
9 9  
1 1 3  
1 2 7  
1 6 9  
 Visit Wi n d o w ( Da ys)  
 
-7/ 0  
± 0  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
0/ 5  
       He patic E ve nt  
1 0. 3. 3  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
       Mali g na nt Ne o plas m  
1 0. 3. 3  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
    I njecti o n Site Reacti o n 
1 0. 3. 3  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
    Me dicati o n Err or, Mis use a n d A b use  
1 0. 3. 3  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
    Tec h nical C o m plai nt  
1 0. 5  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
    La b orat or y Assess me nts  
1 0. 2  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       Bi oc he mistr y  
1 0. 2  
X  
 
X  
 
X  
 
X  
 
 
X  
 
 
X  
 
X  
X  
X  
       A nti b o dies d  
1 0. 2  
 
X  
 
X  
 
X  
 
 
X  
 
 
X  
 
 
X  
 
X  
       Pr ostate S pecific A nti ge n i n ser u m f 
1 0. 2  
X  
 
 
 
 
 
 
 
X  
 
 
 
 
 
X  
 
X  
       C oa g ulati o n P ara meter  
1 0. 2  
X  
 
 
 
X  
 
X  
 
 
X  
 
 
X  
 
X  
X  
X  
       Gl u c ose Meta b olis m  
1 0. 2  
X e 
X  
 
 
 
 
 
 
X  
 
 
 
 
 
X  
 
X  
       Hae mat ol o g y  
1 0. 2  
X  
 
X  
 
X  
 
X  
 
 
X  
 
 
X  
 
X  
X  
X  
       H or m o nes  
1 0. 2  
 
X  
 
 
 
X  
 
 
X  
 
 
X  
 
 
X  
 
X  
       Li pi ds  
1 0. 2  
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
X  
 
X  
       Uri nal ysis  
1 0. 2  
 
X  
 
 
 
X  
 
 
X  
 
 
X  
 
 
X  
 
X  
       2 4 -h o ur uri ne  
1 0. 2  
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
X  
 
 
    P K  
8. 5 ,8. 6  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       Se ma gl uti de  plas ma  
 
 
 
 
X  
 
X  
 
 
X  
 
 
X  
 
 
X  
 
X  
       N N C 0 1 6 5 -1 8 7 5 plas ma  
 
 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
    E C G g 
8. 2. 4  
 
X  
X  
 
X  
 
X  
 
 
X  
 
 
X  
 
X  
X  
X  
    Vital Si g ns  
8. 2. 3  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
    Bi osa m ples f or F ut ure A nal ysis h  
1 0. 8  
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
X  
 
 
    Cli nical O utc o me Ass ess me nts  
8. 2. 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       C -S S R S Baseli ne  
8. 2. 1  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       C -S S R S Si nce Last Visit  
8. 2. 1  
 
X  
 
 
 
 
 
 
X  
 
 
 
 
 
X  
 
 
       P atie nt Healt h Q uesti o n naire - 9 ( P H Q -9)  
8. 2. 1  
X  
X  
 
 
 
 
 
 
X  
 
 
 
 
 
X  
 
 
    A d mi nistrati o n of trial pr o d uct  
6  
 
X  
 
X  
 
X  
 
X  
X  
 
X  
X  
 
X  
X  
 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
 .
-
 |
1
V V- T M F- 5 0 4 2 3 4 5
  Pr ot oc ol  versi o n 4. 0
 |
1 9
 of
1 1 6

Pr ot o c ol  
      
Date:  
0 5 A pril 2 0 2 2  
Stat us:  
Fi n al  
N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
      
V ersi o n:  
4. 0  
P a ge:  
2 0  of 1 1 6  
 
 
 
Pr ot oc ol  
Secti o ns  
Scree ni n g  
R a n d o mis ati o n  
P Y Y a n d Se m a d ose es c al ati o n a n d m ai nte n a nce peri o d  
E n d of tre at me nt  
P ost tre at me nt  
E n d of tri al  
 Visit  
 
V 1  
V 2  
V 3  
V 4  
V 5  
V 6  
V 7  
V 8  
V 9  
V 1 0  
V 1 1  
V 1 2  
V 1 3  
V 1 4  
V 1 5  
V 1 6  
V 1 7  
Ti mi n g i n Wee ks ( W)  
 
-1  
0  
2  
4  
6  
8  
1 0  
1 2  
1 4  
1 6  
1 8  
2 4  
 Ti mi n g of Visit ( Da ys)  
 
-7  
1  
4 *  
1 5  
1 8 *  
2 9  
3 2 *  
4 3  
5 7  
6 0 *  
7 1  
8 5  
8 8 *  
9 9  
1 1 3  
1 2 7  
1 6 9  
 Visit Wi n d o w ( Da ys)  
 
-7/ 0  
± 0  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
± 2  
0/ 5  
    Dr u g acc o u nta bilit y  
 
 
 
 
X  
 
X  
 
X  
X  
 
X  
X  
 
X  
X  
 
 
    Ha n d O ut I D Car d  
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Ha n d O ut D ose Re mi n der Car d  
8  
 
X  
 
X  
 
X  
 
 
X  
 
 
X  
 
 
 
 
 
    Ha n d O ut a n d I nstr uct i n Diar y  
8  
 
X  
 
X  
 
X  
 
 
X  
 
X  
X  
 
X  
 
 
 
    C ollect, Re vie w a n d Tra nscri b e Diaries  
8  
 
 
 
X  
 
X  
 
 
X  
 
 
X  
 
 
X  
 
 
    I nf or mati o n a b o ut uri ne c ollecti o n a n d        
dis pe nsi n g of uri n e c o ntai ner  
8. 2. 5. 1  
X  
 
 
 
 
 
 
 
 
 
 
 
 
X  
 
 
 
    Trai ni n g i n De vices  
6. 1. 1. 1  
 
X  
 
X  
 
X  
 
X  
X  
 
X  
X  
 
X  
 
 
 
*V isit m ust b e at least t w o da ys after or ma x f o ur da ys after pre vi o us d osi n g visit 
a De m o gra p h y c o nsists of date of birt h, se x, et h nicit y a n d race (acc or di n g t o l ocal re g ulati o n). 
b F or fe male s u bj ects of c hil d b eari n g p ote ntial.  
c S m o ki n g is defi ne d as s m o ki n g at least o ne ci garette or e q ui vale nt d ail y.  
d A nti b o d y sa m ples m ust b e ta ke n pre -d ose.  
e O nl y H b A 1c  
f Male s u bj ects o nl y  
g T hree  c o nse c uti ve E C G rec or di n gs m ust b e perf or me d after t he s u bj ect has bee n  place d i n a s upi ne p ositi o n f or at least 1 0 mi n utes  
h D N A sa m ple will o nl y be c ollecte d at visit 2. Ser u m a n d plas ma sa m ples will be c ollecte d at all t he mar ke d visits.
 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
 .
-
 |
1
V V- T M F- 5 0 4 2 3 4 5
  Pr ot oc ol  versi o n 4. 0
 |
2 0
 of
1 1 6

Pr ot o c ol  
      
Date:  
0 5 A pril 2 0 2 2  
Stat us:  
Fi n al  
N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
      
V ersi o n:  
4. 0  
P a ge:  
2 1  of 1 1 6  
 
P art 2  
 
Pr ot oc ol 
Secti o ns  
Scree ni n g  
Se m a d ose esc al ati o n  
R u n i n peri o d  
Se m a gl uti de M ai nte n a nce  
R u n i n peri o d  
R a n d o mis ati o n  
P Y Y d os e esc al ati o n  
 
 
P Y Y M ai nte n a nc e pe ri o d i 
E n d of 
tre at me nt 
E n d of tri al  
 Visit  
 
V 1  
V 2  
V 3  V 4  V 5  
V 6  
V 7  
V 8  V 9  
V 9. 1 * 
V 9. 2 * V 1 0  
V 1 1  
V 1 2  
V 1 3  
V 1 3 b  
V 1 4  
P 1 4 b  
V 1 4c  
P 1 5  V 1 6  
P 1 7  V 1 8  
V 1 9  
 Ti mi n g of Visit Wee ks ( W)  
 
-1  
0  
2  
4  
6  
8  
1 2  
1 6  
2 0  
2 4  
2 8  
3 2  
3 4  
3 6  
3 8  
4 0  
4 2  
4 3  
4 4  
4 5  
4 6  
4 7  
4 8  
5 6  
 Visit Wi n d o w ( Da ys)  
 
-7/ 0  
± 3  
± 3  ± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
0/ 5  
    Atte n d Visit Fasti n g  
5. 3. 1  
 
X  
 
 
 
 
 
 
 
 
 
X  
 
 
 
 
X  
 
X  
 
 
 
X  
X  
    I nf or me d C o nse nt a n d  
    De m o gra p h y a  
1 0. 1. 3  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Eli gi bilit y Criteria  
5. 1 ,5. 2  
X  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Ra n d o misati o n Criteria  
    an d Ra n d o misati o n  
7. 1  
 
 
 
 
 
 
 
 
 
 
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
    Disc o nti n uati o n Criteria  
7. 1  
 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
 
    C o nc o mita nt Me dicati o n  
6. 5  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
    Me dical Hist or y/   
    C o nc o mita nt Ill ness  
8. 2  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Wei g ht Hist or y  
8. 2  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Ris k fact ors  
8. 2  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    T o bacc o Use c 
8. 2  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    C hil d beari n g P ote ntial  
1 0. 4  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Hi g hl y se nsiti ve uri n e  
    pre g na nc y Test b  
1 0. 4  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
 
X  
 
X  
X  
    B o d y Meas ure me nts  
8. 1. 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Hei g ht  
8. 1. 1  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    B o d y Wei g ht  
8. 1. 1  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
 
X  
 
X  
X  
    B MI  
8. 1. 1  
X  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Waist Circ u mfere nce  
8. 1. 1  
 
X  
 
 
 
 
 
 
 
 
 
X  
 
 
 
 
X  
 
X  
 
 
 
X  
 
    P h ysical E x a mi n ati o n  
8. 2. 2  
X  
 
 
 
 
 
 
 
 
 
 
X  
 
 
 
 
 
 
 
 
 
 
X  
 
    A d verse E ve nt  
8. 3 ,1 0. 3  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
    A E Re q uiri n g A d diti o nal  
    Data  
1 0. 3. 3  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       Ac ute Ki d ne y I nj ur y  
1 0. 3. 3  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
 .
-
 |
1
V V- T M F- 5 0 4 2 3 4 5
  Pr ot oc ol  versi o n 4. 0
 |
2 1
 of
1 1 6

Pr ot o c ol  
      
Date:  
0 5 A pril 2 0 2 2  
Stat us:  
Fi n al  
N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
      
V ersi o n:  
4. 0  
P a ge:  
2 2  of 1 1 6  
 
 
Pr ot oc ol 
Secti o ns  
Scree ni n g  
Se m a d ose esc al ati o n  
R u n i n peri o d  
Se m a gl uti de M ai nte n a nce  
R u n i n peri o d  
R a n d o mis ati o n  
P Y Y d os e esc al ati o n  
 
 
P Y Y M ai nte n a nc e pe ri o d i 
E n d of 
tre at me nt 
E n d of tri al  
 Visit  
 
V 1  
V 2  
V 3  V 4  V 5  
V 6  
V 7  
V 8  V 9  
V 9. 1 * 
V 9. 2 * V 1 0  
V 1 1  
V 1 2  
V 1 3  
V 1 3 b  
V 1 4  
P 1 4 b  
V 1 4c  
P 1 5  V 1 6  
P 1 7  V 1 8  
V 1 9  
 Ti mi n g of Visit Wee ks ( W)  
 
-1  
0  
2  
4  
6  
8  
1 2  
1 6  
2 0  
2 4  
2 8  
3 2  
3 4  
3 6  
3 8  
4 0  
4 2  
4 3  
4 4  
4 5  
4 6  
4 7  
4 8  
5 6  
 Visit Wi n d o w ( Da ys)  
 
-7/ 0  
± 3  
± 3  ± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
0/ 5  
       Ac ute Gall bla d der  
       Disease  
1 0. 3. 3  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
       Ac ute P a ncreatitis  
1 0. 3. 3  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
       He patic E ve nt  
1 0. 3. 3  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
       Mali g na nt Ne o plas m  
1 0. 3. 3  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
    Me dicati o n Err or, Mis use  
    a n d A b use  
1 0. 3. 3  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
    I njecti o n Site Reacti o n 
1 0. 3. 3  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
    Tec h nical C o m plai nt  
1 0. 5  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
    La b orat or y Assess me nts  
1 0. 2  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       Bi oc he mistr y  
1 0. 2  
X  
 
 
 
 
 
 
 
 
 
 
X  
 
X  
 
 
X  
 
X  
 
X  
 
X  
X  
       A nti b o dies d  
1 0. 2  
 
X  
 
 
 
 
 
 
 
 
 
X  
X  
X  
 
 
X  
 
X  
 
X  
 
X  
X  
       Bi o mar kers  
1 0. 2  
X f 
X g  
 
 
 
 
 
 
 
 
 
X f g 
 
 
 
 
X f g 
 
X f g 
 
 
 
X f g 
X f g 
       C oa g ulati o n P ara meter  
1 0. 2  
X  
 
 
 
 
 
 
 
 
 
 
X  
 
X  
 
 
X  
 
X  
 
X  
 
X  
X  
       Gl u c ose Meta b olis m  
1 0. 2  
X e 
X  
 
 
 
 
 
 
 
 
 
X  
 
 
 
 
X  
 
X  
 
 
 
X  
X  
       Hae mat ol o g y  
1 0. 2  
X  
 
 
 
 
 
 
 
 
 
 
X  
 
X  
 
 
X  
 
X  
 
X  
 
X  
X  
       H or m o nes  
1 0. 2  
 
X  
 
 
 
 
 
 
 
 
 
X  
 
X  
 
 
X  
 
X  
 
 
 
X  
X  
       Li pi ds  
1 0. 2  
 
X  
 
 
 
 
 
 
 
 
 
X  
 
 
 
 
X  
 
X  
 
 
 
X  
X  
       Uri nal ysis  
1 0. 2  
 
X  
 
 
 
 
 
 
 
 
 
X  
 
X  
 
 
X  
 
X  
 
X  
 
X  
X  
       2 4 -h o ur uri ne  
1 0. 2  
 
 
 
 
 
 
 
 
 
 
 
X  
 
 
 
 
 
 
 
 
 
 
X  
 
P K  
8. 5 ,8. 6  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       Se ma gl uti de plas ma  
 
 
 
 
 
 
 
 
 
 
 
 
X  
 
 
 
 
X  
 
X  
 
 
 
X  
X  
       N N C 0 1 6 5 -1 8 7 5 plas ma  
 
 
 
 
 
 
 
 
 
 
 
 
 
X  
X  
X  
X  
X  
 
X  
 
X  
 
X  
X  
    E C G  
8. 2. 4  
 
X  
 
 
 
 
 
 
 
 
 
X  
 
 
 
 
X  
 
X  
 
 
 
X  
X  
    Vital Si g ns  
8. 2. 3  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
 
X  
 
X  
X  
    Cli nical O utc o me  
    A ssess me nts 
8. 2. 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
       C -S S R S Baseli ne  
8. 2. 1  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
 .
-
 |
1
V V- T M F- 5 0 4 2 3 4 5
  Pr ot oc ol  versi o n 4. 0
 |
2 2
 of
1 1 6

Pr ot o c ol  
      
Date:  
0 5 A pril 2 0 2 2  
Stat us:  
Fi n al  
N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
      
V ersi o n:  
4. 0  
P a ge:  
2 3  of 1 1 6  
 
 
Pr ot oc ol 
Secti o ns  
Scree ni n g  
Se m a d ose esc al ati o n  
R u n i n peri o d  
Se m a gl uti de M ai nte n a nce  
R u n i n peri o d  
R a n d o mis ati o n  
P Y Y d os e esc al ati o n  
 
 
P Y Y M ai nte n a nc e pe ri o d i 
E n d of 
tre at me nt 
E n d of tri al  
 Visit  
 
V 1  
V 2  
V 3  V 4  V 5  
V 6  
V 7  
V 8  V 9  
V 9. 1 * 
V 9. 2 * V 1 0  
V 1 1  
V 1 2  
V 1 3  
V 1 3 b  
V 1 4  
P 1 4 b  
V 1 4c  
P 1 5  V 1 6  
P 1 7  V 1 8  
V 1 9  
 Ti mi n g of Visit Wee ks ( W)  
 
-1  
0  
2  
4  
6  
8  
1 2  
1 6  
2 0  
2 4  
2 8  
3 2  
3 4  
3 6  
3 8  
4 0  
4 2  
4 3  
4 4  
4 5  
4 6  
4 7  
4 8  
5 6  
 Visit Wi n d o w ( Da ys)  
 
-7/ 0  
± 3  
± 3  ± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
0/ 5  
       C -S S R S Si nce Last Visit  
8. 2. 1  
 
X  
 
 
 
 
 
 
 
 
 
X  
 
 
 
 
X  
 
X  
 
 
 
X  
 
    P atie nt Healt h  
    Q uesti o n naire –  9  
    ( P H Q-9)  
8. 2. 1  
X  
X  
 
 
 
 
 
 
 
 
 
X  
 
 
 
 
X  
 
X  
 
 
 
X  
 
    Bi osa m ples f or F ut ure  
    A nal ysis h  
1 0. 8  
 
X  
 
 
 
 
 
 
 
 
 
X  
 
 
 
 
X  
 
X  
 
 
 
X  
 
    I W R S Sessi o n 
6  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
 
X  
 
X  
 
    Treat me nt C o m plia nce  
6. 4  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
 
X  
 
X  
 
    Dr u g Dis pe nsi n g  
6  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
 
X  
 
X  
 
    Ha n d O ut I D Car d  
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Ha n d O ut D ose Re mi n der  
    Car d  
8  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
 
 
 
 
 
    Ha n d O ut a n d I nstr uct i n  
    Diar y  
8  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
 
X  
 
 
 
    C ollect, Re vie w a n d  
    Tra nscri b e Diaries  
 
 
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
 
 
 
X  
 
    I nf or mati o n a b o ut Uri ne  
    c ollecti o n a n d dis pe nsi n g  
    of uri ne c o ntai ner  
8. 2. 5. 1  
 
 
 
 
 
 
 
 
 
 
X  
 
 
 
 
 
 
 
 
 
X  
 
 
 
    Trai ni n g i n De vices  
6. 1. 1. 1  
 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
 
X  
 
 
 
*A d diti o nal visits  9. 1 a n d 9. 2 ha ve bee n acti vate d . 
a De m o gra p h y c o nsists of date of birt h, se x, et h nicit y a n d race (acc or di n g t o l ocal re g ulati o n).  
b F or fe male s u bjects of c hil d beari n g p ote ntial.  
c S m o k i n g is d efi n e d as s m o ki n g at least o ne ci garette or e q ui vale nt dail y. 
d A nti b o d y sa m ples m ust b e ta ke n pre -d ose.  
e O nl y H b A 1c  
f Pr ostate S pecific A nti ge n i n ser u m - o nl y male s u bjects  
g Le pti n a n d S ol u ble Le pti n Rece pt or  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
 .
-
 |
1
V V- T M F- 5 0 4 2 3 4 5
  Pr ot oc ol  versi o n 4. 0
 |
2 3
 of
1 1 6

Pr ot o c ol  
Date:  
0 5 A pril 2 0 2 2  
Stat us:  
Fi n al  
N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
P a ge:  
2 4  of 1 1 6  
h D N A sa m ple will o nl y be c ollecte d  at visit 2. Ser u m a n d plas ma s a m ples will be c ollecte d at all t h e mar ke d visit   
i P Y Y mai nte na nce peri o d f or 1. 0 m g N N C 0 1 6 5 -1 8 7 5 / place b o a n d P Y Y d ose escalati o n a n d mai nte na nce peri o d  f or 2. 0 m g N N C 0 1 6 5-1 8 7 5 / place b o 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
 .
-
 |
1
V V- T M F- 5 0 4 2 3 4 5
  Pr ot oc ol  versi o n 4. 0
 |
2 4
 of
1 1 6

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
Stat us:  
Fi n al  
P a ge:  
2 5  of 1 1 6  
2  I ntr o d ucti o n 
T he pre v ale nce of o besit y has b ee n i ncreasi n g d uri n g t he last 3 0 years1, wit h a c urre nt esti mate d 
w orl d wi de pre v ale nce of m ore t ha n 6 0 0 milli o n pe o ple 2. O besit y is ass ociat e d wit h a n i ncrease d 
ris k of t y p e 2 dia betes ( T 2 D)3, 4, d ysli pi dae mia, h y perte nsi o n5, cardi o vasc ular disease 6, o bstr ucti ve 
slee p a p n oea7, n o n-alc o h olic fatt y li ver disease/ n o n -alc o h olic steat o h e patitis ( N A F L D/ N A S H) 8, 
uri nar y i nc o nti ne nce 9, se veral t y pes of ca ncers1 0, a n d i ncrease d m ortalit y1 1, 1 2. I n a d diti o n t o t hese 
pat h o p h ysi ol o gic c h a n ges, i n di vi d uals wit h o besit y e x perie n ce re d uce d healt h -relate d q ualit y of life, 
i ncl u di n g re d u ce d p h ysic al f u ncti o n1 3 -1 5. I n rec o g niti o n of t he seri o us a n d e xte nsi ve c o nse q ue nces 
of o besit y, s e veral pr ofessi o nal ass ociati o ns a n d or ga nisati o ns w orl d wi de n o w classif y o besit y as a 
disease 1 6 -1 9. 
T he ris k of o besit y -relate d c o m plicati o ns a n d c o m or bi dities i ncreases wit h i ncreasi n g B MI. A 
wei g ht l o ss of 5– 1 0 % h as bee n s h o w n t o ha ve si g nifica nt healt h be n efits i n i n di vi d uals wit h o besit y 
i n ter ms of decreasi n g t h e ris k of T 2 D pr o gressi o n2 0, i m pr o vi n g h y p erte nsi o n2 1, d ysli pi dae mia2 2, 
a n d N A F L D/ N A S H 2 3. I n a d diti o n, i m pr o ve me nts i n patie nt-re p orte d h ealt h-relate d q u alit y of life 
i ncl u di n g p h ysical f u n cti o n ha ve bee n de m o nstrat e d wit h wei g ht l oss2 4. T heref ore, ac hie vi n g a n d 
mai ntai ni n g wei g ht l oss i n i n di vi d uals wit h o besit y is cr u cial. C urre nt sta n dar d of care c o nsists of 
lifest yle c o u nselli n g i ncl u di n g re d uce d-cal ori e diets a n d i ncreas e d p h ysical acti vit y. H o we ver, wit h 
t his first-li ne treat me nt f or o besit y, o nl y o ne i n fi ve i n di vi d uals s uccessf ull y ac hie ve a si g nifi ca nt 
l o n g-ter m wei g ht l oss2 5. 
P har mac ot hera p y ma y t h eref ore ser ve as a val ua bl e a dj u nct t o lifest yl e i nter ve nti o n f or  i n di vi d uals 
wit h o besit y t o ac hie v e a n d s ustai n a cli nicall y rel e va nt wei g ht l oss, i m pr o ve c o m or bi d c o n diti o ns, 
a n d facilitate a healt hier lifest yle. Fe w wei g ht ma n a ge me nt me dicati o ns are c urre ntl y a v aila ble a n d 
t here is a nee d f or m or e effecti ve a n d safe t hera pe utic o pti o ns f or t he treat me nt of o besit y, 
es peciall y treat me nts tar geti n g w ei g ht mai nte n a nce a n d t he treat me nt a n d pre ve nti o n of 
c o m or bi dities 1 6, 2 6 -3 1. 
2. 1  
Tri al r ati o n ale  
T he prese nt tri al is desi g ne d t o i n vesti gate effi cac y a n d s afet y of N N C 0 1 6 5 -1 8 7 5 (s.c.) o nce -wee kl y 
as a d de d t o se ma gl uti de s.c. 2. 4 m g o n ce  wee kl y c o m pare d t o c o nti n ui n g s e ma gl uti de s.c. 2. 4 m g 
o nce  wee kl y al o ne f or wei g ht ma n a ge me nt i n s u bjects wit h o besit y. N N C 0 1 6 5 -1 8 7 5 is a l o n g -
acti n g p e pti de Y Y ( P Y Y) 3 -3 6 a nal o g ue a n d a s electi ve Y 2 rece pt or a g o nist, i nte n de d f or c hr o nic 
wei g ht ma n a ge me nt b y s. c.  a d mi nistrati o n i n c o m bi nati o n wit h se ma gl uti de, a l o n g -acti n g 
gl uc a g o n -li ke pe pti de-1 ( G L P -1) rece pt or a g o nist ( R A). As P Y Y a n d G L P -1 are c o -secrete d fr o m 
i ntesti nal L-cells u p o n fee di n g, t here is c o nsi dera ble i nterest i n i n vesti gati n g t he effect of t hes e  2 
h or m o nes i n c o m bi nati o n. C o -i nf usi o n of P Y Y3 -3 6 a n d G L P -1 has bee n s h o w n t o e x ert a s y n er gistic 
s u p pressi ve effect o n e ner g y i nta k e i n h u ma ns a n d n o n-h u ma n s pecies 3 2, 3 3. 
T he trial c o nsists of t w o parts, Part 1 a n d Part 2. I n Part 1, safet y a n d t olera bilit y will be assesse d 
d uri n g c o -escalati o n of N N C 0 1 6 5 -1 8 7 5 a n d se ma gl uti de. I n Part 2, N N C 0 1 6 5 -1 8 7 5 1 . 0 m g will be 
a d de d t o se ma gl uti de s.c. 2. 4 m g at stea d y st ate t o c o m pare t he effi cac y a n d safet y of 
N N C 0 1 6 5 -1 8 7 5 a d de d o n t o se ma gl uti de s.c. 2. 4 m g vers us c o nti n ui n g se ma gl uti de s.c. 2. 4 m g 
al o ne. T he i nitial r u n -i n peri o d i n Part 2 of t he tri al ( Part 2a) all o ws f or wei g ht l oss t o be o btai ne d 
wit h se ma gl uti de s.c. 2. 4 m g, bef ore t he a d diti o n of N N C 0 1 6 5 -1 8 7 5 1 . 0 m g t h us all o wi n g f or a n y 
N N 9 7 7 5- 4 7 0 8
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Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
2 6  of 1 1 6  
 
a d diti o nal wei g ht l oss o btai ne d b y t his a d diti o n t o be c o m pare d wit h t he wei g ht l oss o btai ne d wit h 
c o nti n ui n g se ma gl uti de s.c. 2. 4 m g o nl y. F urt her m ore , safet y e val uati o n of t he N N C 0 1 6 5 -1 8 7 5 
2. 0  m g d ose will be perf or me d i n a s mall c o h ort. T his trial will pr o vi de pr o of of pri nci ple  a n d s afet y 
e val uati o n t o g ui d e f urt h er cli nical de vel o p me nt. 
2. 2  
B ac k gr o u n d  
2. 2. 1  
Pe pti de Y Y ( N N C 0 1 6 5 -1 8 7 5)  
E n d o ge n o us P Y Y is secrete d t o get her wit h G L P -1 b y L -cells i n t he distal g ut i n res p o nse t o n utrie nt 
i nta ke. After s ecreti o n, P Y Y is clea ve d i nt o its acti ve f or m P Y Y 3 -3 6, w hic h has bee n s h o w n t o 
re d uce f o o d i nta ke a n d l o wer b o d y w ei g ht i n se v eral a ni mal s pecies a n d i n h u ma ns 3 4. T he 
mec ha nis m of acti o n is m ost li kel y acti vati o n of t he Y 2 rece pt or e x presse d i n t he h y p ot hala m us, a 
ke y re gi o n of t he brai n f or re g ulati o n of e n er g y h o me ostasis 3 5. 
O ne p hase 1 tri al wit h N N C 0 1 6 5 -1 8 7 5 has rece ntl y bee n c o m plete d. A c o m pre he nsi ve re vie w of 
res ults fr o m t he n o n-cli ni cal a n d cli nical st u dies of N N C 0 1 6 5 -1 8 7 5 ca n b e f o u n d i n t he c urre nt 
e diti o n of t he I n vesti gat or’s Br oc h ure3 6 a n d a n y u p dates here of.  
2. 2. 2  
Gl uc a g o n -li ke pe pti de-1 (se m a gl uti de)  
G L P -1 R A is a p h ysi ol o gic al re g ulat or of a p petite a n d G L P -1 rece pt ors are prese nt i n se veral areas 
of t he brai n i n v ol ve d i n a p petite re g ulati o n 3 7. Se ma gl uti de is a  o n ce -wee kl y G L P -1 a nal o g ue 
a p pr o ve d f or t he treat me nt of a d ults wit h T 2 D at a d ose of 1. 0 m g ( Oze m pic ® ) a n d is c urre ntl y 
u n der de vel o p me nt b y N o v o N or dis k f or wei g ht ma na ge me nt wit h o nce -wee kl y se ma gl uti de s.c. 
d oses of 2. 4 m g.  
A gl o bal p h ase 3a cli nical de vel o p me nt pr o gra m m e wit h o nce -wee kl y se m a gl uti de s.c. 2. 4 m g has 
bee n c o m plete d i n s u bjects wit h o ver wei g ht or o besit y ( S T E P pr o gra m me). T he pr o gra m me 
c o nsist e d of f o ur trials  a n d e nr olle d a p pr o xi matel y 4, 5 0 0 a d ults wit h o ver wei g ht or o b esit y. T h e 
lar gest trial ( N N 9 5 3 6-4 3 7 3; S T E P  1) i n vesti gate d t he efficac y a n d safet y of o nce -wee kl y 
se ma gl uti de s. c. 2. 4 m g o n b o d y w ei g ht o v er 6 8 wee ks c o m pare d t o place b o i n 1, 9 6 1 a d ults wit h 
o ver wei g ht or o b esit y wit h c o m or bi dities, b ot h i n c o nj u ncti o n wit h lifest yle i nt er ve nti o n. S u bjects 
treate d wit h se ma gl uti de s.c. 2. 4 m g ac hie ve d a m ea n wei g ht l oss of 1 4. 9 %, fr o m a baseli ne b o d y 
wei g ht of 1 0 5. 3 k g, c o m pare d t o a 2. 4 % wei g ht l oss wit h place b o. I n a d diti o n, 8 6 .4 % of t h ose w h o 
recei v e d se ma gl uti de s.c. 2. 4 m g reac h e d a wei g ht l oss of 5 % or m ore after 6 8 wee ks, c o m p are d t o 
3 1. 5 % wit h place b o. Se ma gl uti de s.c. 2. 4 m g a p peare d t o b e a safe a n d well t olerate d pr ofile i n li n e 
wit h w hat has pre vi o usl y bee n o bser ve d f or s e ma gl uti de (ref). T h e m ost c o m m o n a d verse e v e nts 
( A Es) a m o n g s u bjects treate d wit h se ma gl uti de s.c. 2. 4 m g were gastr oi ntesti nal e ve nts. M ost were 
tra nsie nt a n d mil d or m o derate i n se v erit y.  
A c o m pre he nsi v e re vie w of res ults fr o m t he n o n -cli nical a n d cli nical st u dies of se ma gl uti de ca n b e 
f o u n d i n t he c urre nt e diti o n of t he In vesti gat or’s Br oc h ure  a n d a n y u p d ates here of 3 8. 
2. 2. 3  
Tri al p o p ul ati o n  
T he trial p o p ulati o n will c o nsist of s u bjects wit h o besit y ( B MI 3 0. 0 -4 5. 0 k g/ m 2, b ot h i ncl usi ve). 
T hese s u bjects re pres e nt a cli nicall y rele va nt p o p ulati o n f or p har mac ol o gi cal wei g ht ma na ge m e nt 
N N 9 7 7 5- 4 7 0 8
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Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
Stat us:  
Fi n al  
P a ge:  
2 7  of 1 1 6  
as t he y are at si g nifica nt ris k f or wei g ht -relate d c o m or bi dities a n d m ortalit y a n d are li kel y t o be nefit 
fr o m wei g ht re d u cti o n. 
2. 3  
Be nefit -ris k assess me nt  
Mai n be nefits a n d ris ks  are descri be d i n t he bel o w secti o ns. M ore detaile d i nf or mati o n a b o ut t he 
k n o w n a n d e x pecte d be n efits a n d ris ks a n d reas o n a bl y e x pecte d A Es of N N C 0 1 6 5 -1 8 7 5 ma y b e 
f o u n d i n t he c urre nt e diti o n of t he I n vesti gat or’s Br oc h ure3 6 a n d a n y u p dates here of.  
M ore detaile d i nf or mati o n a b o ut t he k n o w n a n d e x pecte d be nefits a n d ris ks a n d reas o n a bl y 
e x pecte d A Es of se ma gl uti de ma y b e f o u n d i n t he c urre nt e diti o n of t he i n vesti gat or’s br oc h ure a n d 
a n y u p d ates here of 3 8.  
T he p ote ntial ris ks descri be d i n t he bel o w secti o n are bas e d o n fi n di n gs i n n o n -cli nical st u dies wit h 
N N C 0 1 6 5 -1 8 7 5 a n d N N C 0 1 6 5 -1 8 7 5 i n c o m bi nati o n wit h se ma gl uti de. T h e i de ntifie d a n d p ote ntial 
ris ks descri be d i n t he bel o w secti o n are base d o n fi n di n gs i n n o n -cli nical st u dies a n d cli nical trials 
wit h se ma gl uti de as well as ot her G L P -1 R As. F or eac h of t h ese ris ks, miti gati n g acti o ns ha ve bee n 
i m ple me nte d t o mi ni mise t he ris ks f or s u bjects e nr olle d i n t his trial. 
N N 9 7 7 5- 4 7 0 8
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
2 8  of 1 1 6  
 
2. 4  
Ris k assess me nt  
P ote nti al ris k of cli nic al 
si g nific a nce 
S u m m ar y of d at a/r ati o n ale f or 
ris k 
Miti g ati o n str ate g y  
 
Tri al tre at me nt  N N C 0 1 6 5 -1 8 7 5  
I ncrease d bl o o d press ure 
I ncrease d bl o o d press ure has b ee n 
o bser ve d i n a safet y p har mac ol o g y 
st u d y i n rats.  
S yst olic, diast olic bl o o d press ure a n d 
p ulse rate will be assesse d fre q ue ntl y  
 
P a pillar y necr osis i n t he ki d ne ys  
A bilateral re nal pa pillar y necr osis 
has bee n o bser ve d i n o ne male i n a 
t o xic ol o g y st u d y i n rats. 
 
E x p os ure ca p is base d o n t he hi g hest 
d ose i n 1 6 -wee k pi g N O A E L . 
Ki d n e y f u ncti o n will be m o nit ore d 
b y bi oc he mistr y assess me nt a n d 
uri nal ysis.  
R o uti ne p har mac o vi gila nce will be 
e xec ute d t hr o u g h o ut t he trial.  
Gastric necr osis  
Diste n de d st o mac h at necr o ps y, 
i nfla m mati o n a n d necr osis i n t he 
m uc osa a n d s u b m uc osa of t he 
n o n -gla n d ular st o mac h has bee n 
o bser ve d i n a d ose ra n ge fi n di n g 
st u d y i n rats. 
I n s o me a ni mals, t he necr osis was 
tra ns m ural, wit h s prea di n g t o ot her 
or ga ns a n d t here b y ca usi n g l o cal 
perit o nitis.  
Fre q ue nt site visits wit h vital si g n s, 
p h ysical e xa mi nati o n a n d safet y 
la b orat or y assess me nts is i ncl u de d. 
R o uti ne p har mac o vi gila nce will be 
e xec ute d t hr o u g h o ut t he trial.  
 
C ha n ge i n male re pr o d ucti ve or ga ns  
Mar ke d decrease i n pr ostate gl a n d 
a n d se mi nal vesicles wei g hts a n d 
ass ociate d wit h hist o pat h ol o g y 
fi n di n gs (e pit helial atr o p h y i n t he 
pr ostate a n d  decrease d secreti o n i n 
t he pr ostate a n d se mi nal vesicl es) 
was o bser ve d i n t o xic ol o g y st u dies 
i n rats. 
S u bj ects wit h a hist or y of pr ostate 
disease will n ot be i ncl u de d i n t he 
trial. 
H or m o nes ( F S H, L H, pr olacti n, 
estra di ol  a n d test oster o ne) a n d 
pr ostate s pecific a nti ge n ( P S A) will 
be assesse d.  
I ncrease d ti dal v ol u me 
I ncrease d res pirat or y rate a n d mi n ute 
v ol u me a n d i ncrease d ti dal v ol u me 
has bee n o bser ve d i n safet y 
p har mac ol o g y st u dies i n rats.  
Vital si g ns i ncl u di n g res pirat or y rate 
a n d o x y ge nati o n will be m o nit ore d.  
 
Na usea, diarr h oea, v o miti n g a n d 
c o nsti pati o n  
Na usea, diarr h oea, v o miti n g a n d 
c o nsti pati o n has bee n o bser ve d w he n 
treati n g s u bj ects wit h 
N N C 0 1 6 5 -1 8 7 5 a n d has bee n 
o bser ve d w he n treati n g s u bj ects wit h 
P Y Y 3 -3 6. 
A l o w starti n g d ose a n d d ose 
escalati o n ste ps will be i m ple me nte d.  
R o uti ne p har mac o vi gila nce will be 
e xec ute d t hr o u g h o ut t he trial . 
I ncrease d uri nar y calci u m 
c o nce ntrati o n  
I ncrease d uri nar y e xcreti o n of 
calci u m has bee n o bser ve d i n a 
t o xicit y st u d y i n rats. 
Uri nar y i o n c o nce ntrati o n will be 
m o nit ore d b y fre q ue nt uri nal ysis a n d 
b y 2 4 -h o ur uri ne c ollecti o ns, 
i ncl u di n g assess me nt of uri nar y i o n 
e xcreti o n.  
I m m u n o ge nicit y ( Aller gic reacti o ns / 
a nti b o d y f or mati o n) 
As is t he case wit h all pr otei n -base d 
p har mace uticals, s u bj ects treate d 
wit h N N C 0 1 6 5 -1 8 7 5 are at a ris k of 
de vel o pi n g i m m u n o ge nic a n d 
aller gic reacti o ns.  
N N C 0 1 6 5 -1 8 7 5 is c o ntrai n dicate d i n  
pers o ns wit h k n o w n or s us pecte d  
h y perse nsiti vit y t o a n y of t he trial 
pr o d uct c o m p o ne nts, i ncl u di n g  
e xci pie nts.  
S u bj ects will be cl osel y m o nit ore d 
f or h y perse nsiti vit y reacti o ns after 
a d mi nistrati o n of t he trial pr o d uct  
 
 
N N 9 7 7 5- 4 7 0 8
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
2 9  of 1 1 6  
 
I nj ecti o n site reacti o ns 
As is t he case wit h all pr otei n -base d 
p har mace uticals, s u bj ect treate d wit h 
N N C 0 1 6 5 -1 8 7 5 are at ris k of 
de vel o pi n g i nj ecti o n site reacti o ns  
Fre q ue nt site visits wit h p h ysi cal 
e xa mi nati o n is i ncl u de d  
Tri al tre at me nt N N C 0 1 6 5 -1 8 7 5 i n c o m bi n ati o n wit h se m a gl uti de  
Decrease d gastric e m pt yi n g a n d 
decrease d i ntesti nal m otilit y  
E n ha nce d decrease i n  i ntesti nal 
m otilit y a n d gastric  e m pt yi n g w he n 
c o m pare d t o si n gle c o m p o ne nts  
Gastr oi ntesti nal si g ns a n d s y m pt o ms 
a n d c ha n ges i n b o wel ha bits will be 
m o nit ore d b y p h ysical e xa mi nati o n 
a n d A E re p orti n g  
R o uti ne p har mac o vi gila nce will be 
e xec ute d t hr o u g h o ut t he trial  
I ncrease d uri ne v ol u me i ncl. 
I ncrease d uri nar y calci u m 
c o nce ntrati o n  
 
I ncreases i n uri nar y v ol u me res ulti n g 
i n l o wer urinar y c o nce ntrati o n of 
calci u m, p otassi u m, c hl ori de, 
p h os p h or us, creati ni ne has bee n 
o bser ve d i n a c o m bi nati o n t o xicit y 
st u d y i n rats. 
Uri ne v ol u me will be m o nit ore d b y 
2 4 -h o ur uri ne v ol u me c ollecti o ns. 
Uri nar y i o n c o nce ntrati o n will be 
m o nit ore d b y fre q ue nt uri nal ysis a n d 
b y 2 4 -h o ur uri ne c ollecti o ns, 
i ncl u di n g assess me nt of uri nar y i o n 
e xcreti o n. 
Tri al tre at me nt se m a gl uti de  
Gastr oi ntesti nal A E  
C o nsiste nt wit h fi n di n gs wit h ot her 
G L P -1 R As, t he m ost fre q ue ntl y 
re p orte d A E i n cli nical trials wit h 
se ma gl uti de were gastr oi ntesti nal 
A Es.  
A l o w starti n g d ose a n d d ose 
escalati o n ste ps will be 
i m ple me nte d.  
C h olelit hiasis  
Fre q ue ntl y re p orte d gall bla d der 
e ve nts i n t he p hase 2 wei g ht 
ma na ge me nt trial ( N N 9 5 3 6 -4 1 5 3) 
a n d were i n a fe w i nsta nces 
c o -re p orte d wit h t he e ve nt 
a dj u dicati o n c o m mittee c o nfir me d 
ac ute pa ncreatitis.  
If c h olelit hiasis is s us pecte d, 
a p pr o priate cli nical f oll o w -u p is t o 
be i nitiate d at t he i n vesti gat or’s 
discreti o n  
Ac ute pa ncreatitis  
Ac ute pa ncreatitis has bee n o bser ve d 
wit h t he use of  G L P -1 R A dr u g 
class.  
S u bj ects wit h a hist or y of c hr o nic 
pa ncreatitis or rece nt pa ncreatitis 
will n ot be e nr olle d i n t he trial. I n 
a d diti o n, trial pr o d uct s h o ul d be 
disc o nti n ue d i n case of s us pici o n of 
pa ncreatitis i n acc or da nce t o Secti o n 
7. 1 . 
P ote nti al ris k of cli nic al 
si g nific a nce 
S u m m ar y of d at a/r ati o n ale f or 
ris k 
Miti g ati o n str ate g y  
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 0  of 1 1 6  
 
P ote nti al ris k of cli nic al 
si g nific a nce 
S u m m ar y of d at a/r ati o n ale f or 
ris k 
Miti g ati o n str ate g y  
 
Me d ullar y t h yr oi d ca ncer ( M T C) 
( base d o n n o n-cli nical d ata)  
Pr oliferati ve t h yr oi d C -cell c ha n ges 
were see n i n t he m o use a n d rat 
carci n o ge nicit y st u dies after dail y 
e x p os ure t o se ma gl uti de f or 2 years. 
N o h y per plasia was o bser ve d i n 
m o n ke ys after 5 2 wee ks e x p os ure u p 
t o 1 3-f ol d a b o ve t he cli nical plas ma 
e x p os ure at 2. 4 m g/ wee k. I n cli nical 
trials wit h se ma gl uti de, t here ha ve 
bee n n o cli nicall y rele va nt c ha n ges 
i n calcit o ni n le vels. T he C-cell 
c ha n ges i n r o de nts are me diat e d b y 
t he G L P-1 rece pt or, w hic h is n ot 
e x presse d i n t he n or mal h u ma n 
t h yr oi d. Acc or di n gl y, t he ris k of 
G L P -1 rece pt or -me diate d C -c ell 
c ha n ges i n h u ma ns is c o nsi der e d t o 
be l o w.  
E xcl usi o n criteria relate d t o me dical 
hist or y of m ulti ple e n d ocri ne 
ne o plasia t y pe 2 ( M E N 2) or M T C 
ha ve bee n i m ple me nte d.  
P a ncreatic ca ncer  
T here is c urre ntl y n o s u p p ort fr o m  
n o n -cli nical st u dies, cli nical trials or 
p ost -mar keti n g data t hat G L P -1 R A 
base d t hera pies i ncrease t he ris k of 
pa ncreatic ca ncer, b ut pa ncreatic 
ca ncer has bee n classifie d as a 
p ote ntial class ris k of G L P -1 R As b y 
E ur o pea n Me dici nes A ge nc y.  
S u bj ects wit h  a hist or y of mali g na nt 
ne o plas ms wit hi n t he past 5 years 
pri or t o scree ni n g will be e xcl u de d 
fr o m t he trial. 
Aller gic reacti o ns  
As is t he case wit h all pr otei n -base d 
p har mace uticals, s u bj ects treate d 
wit h se ma gl uti de are at ris k of 
de vel o pi n g i m m u n o ge nic  a n d 
aller gic reacti o ns.  
S u bj ects wit h k n o w n or s us pecte d 
h y perse nsiti vit y t o se ma gl uti d e or 
relate d pr o d ucts will n ot be e nr olle d.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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3 0
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 1  of 1 1 6  
 
Tri al pr oce d ures  
P ote nti al ris k of cli nic al 
si g nific a nce 
S u m m ar y of d at a/r ati o n ale f or 
ris k 
Miti g ati o n str ate g y  
 
C O VI D -1 9:  
1. Ris k of C O VI D -1 9 i nfecti o n i n 
relati o n t o partici pati o n i n trial 
 
2. E xte nsi o n of se ma gl uti de treat me nt 
i n P art 2 a. 
 
3. Ot her ris ks relate d t o C O VI D-1 9  
1. S u bj ects ma y be e x p ose d t o t he 
ris k of C O VI D-1 9 tra ns missi o n a n d 
i nfecti o n i n relati o n t o site visits if a n 
o ut brea k is o n g oi n g i n t he gi ve n 
c o u ntr y  
2. E xte nsi o n of se ma gl uti de treat me nt 
f or s o me s u bj ects i n P art 2a ca n be 
c o nsi dere d i n case of a n o ut brea k of 
C O VI D -1 9.  
 
1. T he ris k of C O VI D -1 9 
tra ns missi o n i n relati o n t o site visits 
is o verall c onsi dere d t o be l o w; 
h o we ver, t his ma y var y bet we e n 
ge o gra p hical area. T o mi ni mis e t he 
ris k as m uc h as p ossi ble, t he 
f oll o wi n g meas ures ha ve bee n ta ke n: 
Ca uti o us s u bj ect recr uit me nt 
pla n ni n g e ns ures c o ntr olle d s u bj ect 
e nr ol me nt at sites w here t he 
C O VI D -1 9 pa n de mic is e val uate d t o 
be s ufficie ntl y u n der c o ntr ol, a n d 
w here healt h care res o urces ar e 
e val uate d t o be a de q uate  
G ui da nce is pr o vi de d t o site staff t o 
re q uest t hat o nsite visits are pla n ne d 
t o be as s h ort as p ossi ble. P h ysical 
c o ntact bet wee n s u bj ects a n d site 
staff will b e li mite d t o t he e xte nt 
p ossi ble, a n d pr otecti ve meas ures 
will be i m ple me nte d e. g., use of 
mas ks, sa nitisers, n o aer os ol -
ge nerati n g pr oce d ures, etc. acc or di n g 
t o l ocal re q uire me nts 
2. I n case sites i n P art 2a are bei n g 
te m p oraril y cl ose d d ue t o t he 
C O VI D -1 9 pa n de mic, s u bj ects will 
be all o we d t o e xte n d treat me nt wit h 
se ma gl uti de bef ore a d di n g 
N N C 0 1 6 5 -1 8 7 5. T his is all o we d i n 
or der t o miti gate t hat s u bj ects w o ul d 
ot her wise ha ve t o be disc o nti n ue d if 
it was n ot p ossi ble t o atte n d a site 
vi sit t o a d d N N C 0 1 6 5-1 8 7 5 
acc or di n g t o t he fl o wc hart sc he d ule.  
3. T o mi ni mise ot her ris ks relate d t o 
C O VI D -1 9 t he f oll o wi n g meas ures 
ha ve bee n ta ke n.  
 
 
Eli gi bilit y criteria:  
C O VI D -1 9 testi n g a n d dia g n osis 
s h o ul d be d o ne acc or di n g t o l ocal 
re q uire me nts. 
C o -partici pati o n i n C O VI D -1 9 
st u dies is n ot all o we d 
Treat me nt wit h N N C 0 1 6 5 -1 8 7 5 a n d 
se ma gl uti de: 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 2  of 1 1 6  
 
C O VI D -1 9 testi n g s h o ul d be 
perf or me d acc or di n g t o l ocal 
re q uire me nts. 
I n case of a s u bj ect has a p ositi ve 
C O VI D -1 9 test, t he disc o nti n uati o n 
of t he trial pr o d u ct is at t he 
discreti o n of t he i n vesti gat or 
acc or di n g disc o nti n uati o n crit eria n o. 
1. S u bj ects rec o vere d fr o m a 
C O VI D -1 9 i nfecti o n are all o we d t o 
res u me trial pr o d uct at t he dis creti o n 
of t he i n vesti gat or.  
T he s u bj ect s h o ul d f oll o w t he g ui de 
f or misse d d oses (see Secti o n 6. 1 ) if 
treat me nt s h o ul d be res u me d. 
Ot her  
Pre g na nc y  
Se ma gl uti de  
St u dies i n a ni mals ha ve s h o w n 
re pr o d ucti ve t o xicit y. T here is 
li mite d data fr o m t he use of 
se ma gl uti de i n pre g na nt w o me n.  
 
N N C 0 1 6 5 -1 8 7 5:  
N o n o n -cli nical re pr o -t o xic ol o g y 
data or cli nical data are a vaila ble.  
Se ma gl uti de a n d N N C 0 1 6 5 -1 8 7 5 
s h o ul d n ot be use d d uri n g 
pre g na nc y. E xcl usi o n a n d 
disc o nti n uati o n criteria relate d t o 
pre g na nc y ha ve bee n i m ple me nte d.  
 
F or g ui da nce o n c o ntrace pti o n f or 
w o me n of c hil d beari n g p ote ntial; 
refer t o A p pe n di x 4, Secti o n 1 0. 4   
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 3  of 1 1 6  
 
2. 4. 1  
Be nefit assess me nt  
S u bjects will be treate d wit h a re gi me n a ntici pat e d t o be better t ha n or e q u al t o t he wei g ht 
ma na ge me nt t he y recei ve at t he ti me of e ntr y i nt o t he trial. I n a d diti o n, all s u bjects will u n der g o 
t h or o u g h me dical e val u ati o ns/assess me nts d uri n g t he trial, i ncl u di n g p h ysic al e xa ms, bl o o d tests 
a n d E C Gs.  
2. 4. 2  
O ver all be nefit -ris k c o ncl usi o n  
Ta ki n g i nt o acc o u nt t he meas ures ta k e n t o mi ni mise ris k t o s u bjects partici pati n g i n t his trial, t he 
p ote ntial ris ks i de ntifie d i n ass ociati o n wit h N N C 0 1 6 5 -1 8 7 5 i n c o m bi nati o n wit h se ma gl uti de are 
j ustifie d b y t he a ntici pat e d be nefits t hat ma y be aff or de d t o s u bjects wit h o besit y 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 4  of 1 1 6  
 
3  O bjecti ves a n d e n d p oi nts  
3. 1  
Pri m ar y, sec o n d ar y a n d e x pl or at or y o bjecti ves a n d esti m a n ds  
O bjecti ves  
P art 1  
Pri m ar y o bjecti ve  
T o e val uate t he s afet y a n d t olera bilit y of c o -es calati o n of o nce -wee kl y d oses of N N C 0 1 6 5 -1 8 7 5 a n d 
se ma gl uti de a d mi nistere d si m ulta ne o usl y as se parate d oses i n s u bjects wit h o besit y.  
P art 2  
Pri m ar y o bjecti ve  
T o c o m pare t h e effect of N N C 0 1 6 5 -1 8 7 5  1. 0 m g  a d de d o n t o se ma gl uti de s.c. 2. 4 m g at stea d y 
state, vers us c o nti n ui n g se ma gl uti de s.c. 2. 4 m g al o ne, o n b o d y wei g ht i n s u bjects wit h o besit y.  
Sec o n d ar y o bjecti ve  
T o c o m pare t h e effect of N N C 0 1 6 5 -1 8 7 5 1. 0 m g a d de d o n t o se ma gl uti de s.c. 2. 4 m g at stea d y state 
vers us c o nti n ui n g s e ma gl uti de s.c. 2. 4 m g al o n e i n s u bjects wit h o besit y o n:  
•  Gl ycae mic c o ntr ol  
•  Waist circ u mfere n ce  
•  Car di o vasc ular ris k fact ors  
T o c o m pare t h e safet y a n d t olera bilit y of N N C 0 1 6 5 -1 8 7 5 1. 0 m g a n d N N C 0 1 6 5 -1 8 7 5 2. 0 m g a d de d 
o n t o se ma gl uti de s.c. 2. 4  m g vers us c o nti n ui n g se ma gl uti de s.c. 2. 4 m g al o ne i n s u bjects wit h 
o besit y.  
Esti m a n ds  
Esti ma n ds a p pl y f or st atistical a nal ysis of Part 2.  
Pri m ar y esti m a n d  
T he esti ma n d will q ua ntif y t he a vera ge tr eat me nt of N N C 0 1 6 5 -1 8 7 5 1. 0 m g as a n a d d o n t o 
se ma gl uti de 2. 4 m g relati ve t o place b o as a n a d d o n t o se ma gl uti de 2. 4 m g i n all ra n d o mise d 
s u bjects re gardless of treat me nt disc o nti n uati o n a n d resc ue i nter ve nti o ns (a nti -o besit y dr u gs or 
de vices, or b ariatric s ur ger y) wit h res p ect t o perce nt c ha n ge i n b o d y wei g ht fr o m wee k 3 2  t o 
wee k  4 8  i n all ra n d o mise d s u bjects w h o are a ble t o reac h t h e tar get d ose of se magl uti de d uri n g 
3 2  wee ks of r u n -i n wit h escalati n g se ma gl uti de d oses. 
 
 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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3 4
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 5  of 1 1 6  
 
 
A d diti o n al esti m a n d  
T he esti ma n d will q ua ntif y t he a vera ge tr eat me nt of N N C 0 1 6 5 -1 8 7 5  1. 0  m g  as a n a d d o n t o 
se ma gl uti de 2. 4 m g relati ve t o place b o as a n a d d o n t o se ma gl uti de 2. 4 m g i n all s u bjects w h o 
re mai n o n t heir ra n d o mise d treat me nt f or t he e ntire pla n ne d d urati o n of t he treat me nt peri o d a n d d o 
n ot start a n y resc u e i nter ve nti o n (a nti -o besit y dr u gs or de vices, or bariatri c s ur ger y) wit h res pect t o 
perce n t c ha n ge i n b o d y wei g ht fr o m wee k 3 2  t o wee k 48  i n all ra n d o mise d s u bjects w h o are a ble t o 
reac h t h e tar get d ose of s e ma gl uti de d uri n g 3 2  wee ks of r u n -i n wit h es calati n g se ma gl uti de d oses. 
 
3. 2  
Pri m ar y, sec o n d ar y a n d e x pl or at or y e n d p oi nts  
3. 2. 1  
Pri m ar y e n d p oi nt  
P art 1  
E n d p oi nt title  
Ti me fr a me  
U nit  
N u m ber of treat me nt -e mer ge nt 
a d verse e ve nts ( T E A Es)  
Fr o m ti me of d osi n g ( da y 1) t o 
f oll o w-u p ( wee k 2 4)  
N u m ber of e ve nts  
Attri b ute  
 
Tre at me nt  
N N C 0 1 6 5 -1 8 7 5 as a n a d d o n t o se ma gl uti de 2. 4 m g vers us place b o as a n a d d o n t o 
se ma gl uti de 2. 4 m g 
 
P o p ul ati o n  
All s u bj ects ra n d o mise d t o 1. 0 m g  N N C 0 1 6 5 -1 8 7 5 f or w h o m se ma gl uti de ha s 
bee n escalate d t o t he tar get d ose wit h se ma gl uti de 2. 4 m g at wee k 2 8  a n d at tar get 
d ose at t he ra n d o misati o n visit ( wee k 3 2 ) 
E n d p oi nt  
P erce nt c ha n ge i n b o d y wei g ht fr o m wee k 3 2  t o wee k 48  
I nterc urre nt e v e nts 
Treat me nt disc o nti n uati o n : tre at me nt p olic y strate g y 
Resc ue i nter ve nti o ns (a nti -o besit y dr u gs or de vices, or bariatric s ur ger y): treat me nt 
p olic y/effecti ve ness p olic y str ate g y  
P o p ul ati o n -le vel s u m m ar y 
Differe nce i n a vera ge perce nt c ha n ge i n b o d y wei g ht bet wee n N N C 0 1 6 5 -1 8 7 5 
1. 0  m g as a n a d d o n t o se ma gl uti de s.c. 2. 4 m g v ers us place b o as a n a d d o n t o 
se ma gl uti de s.c. 2. 4 m g  
Attri b ute  
 
Tre at me nt  
N N C 0 1 6 5 -1 8 7 5 as a n a d d o n t o se ma gl uti de 2. 4 m g vers us place b o as a n a d d o n t o 
se ma gl uti de 2. 4 m g 
P o p ul ati o n  
All s u bj ects ra n d o mise d t o 1. 0 m g N N C 0 1 6 5-1 8 7 5 f or w h o m se ma gl uti de has 
bee n escalate d t o t he tar get d ose wit h se ma gl uti de 2. 4 m g at wee k 2 8  a n d at tar get 
d ose at t he ra n d o misati o n visit ( wee k 3 2 ) 
E n d p oi nt  
P erce nt c ha n ge i n b o d y wei g ht fr o m wee k 3 2  t o wee k 48  
I nterc urre nt e v e nts 
Treat me nt disc o nti n uati o n: h y p ot hetical strate g y  
Resc ue i nter ve nti o ns (a nti -o besit y dr u gs or de vices or bariatric s ur ger y): 
h y p ot hetical/efficac y strate g y   
P o p ul ati o n -le vel s u m m ar y 
Differe nce i n a vera ge perce nt c ha n ge i n b o d y wei g ht bet wee n N N C 0 1 6 5-1 8 7 5 
1. 0  m g as a n a d d o n t o se ma gl uti de s.c. 2. 4 m g v ers us place b o as a n a d d o n t o 
se ma gl uti de s.c. 2. 4 m g 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 6  of 1 1 6  
 
P art 2  
Pri mar y e n d p oi nt f or N N C 0 1 6 5 -1 8 7 5 1. 0 m g as a n a d d o n t o se ma gl uti de 2. 4 m g vers us place b o  
1. 0  m g  as a n a d d o n t o se ma gl uti de 2. 4 m g:  
E n d p oi nt title  
Ti me fr a me  
U nit  
C ha n ge i n b o d y wei g ht  
Fr o m ra n d o misati o n ( wee k 3 2 ) t o 
e n d of treat me nt ( wee k 4 8 ) 
perce nta ge  
3. 2. 2  
Sec o n d ar y e n d p oi nts  
3. 2. 2. 1  
C o nfir m at or y s ec o n d ar y e n d p oi nts  
N ot a p plica ble  
3. 2. 2. 2  
S u p p orti ve sec o n d ar y e n d p oi nts  
P art 2  
S u p p orti ve sec o n dar y e n d p oi nts f or N N C 0 1 6 5 -1 8 7 5  1. 0 m g  as a n a d d o n t o se ma gl uti de 2. 4 m g 
vers us place b o  1. 0  m g  as a n a d d o n t o se ma gl uti de 2. 4 m g : 
E n d p oi nt title  
Ti me fr a me  
U nit  
C ha n ge i n b o d y wei g ht  
Fr o m ra n d o misati o n ( wee k 3 2 ) t o 
e n d of treat me nt ( wee k 4 8 ) 
k g  
C ha n ge i n H b A 1 c 
Fr o m ra n d o misati o n ( wee k 3 2 ) t o 
e n d of treat me nt ( wee k 4 8 ) 
P erce nta ge p oi nt  
C ha n ge i n fasti n g plas ma gl uc ose  
Fr o m ra n d o misati o n ( wee k 3 2 ) t o 
e n d of treat me nt ( wee k 4 8 ) 
m m ol/l  
C ha n ge i n fasti n g i ns uli n  
Fr o m ra n d o misati o n ( wee k 3 2 ) t o 
e n d of treat me nt ( wee k 4 8 ) 
p m ol/l  
C ha n ge i n waist circ u mfere nc e  
Fr o m ra n d o misati o n ( wee k 3 2 ) t o 
e n d of treat me nt ( wee k 4 8 ) 
c m 
Relati ve c ha n ge i n t otal c h olester ol  
Fr o m ra n d o misati o n ( wee k 3 2 ) t o 
en d of treat me nt ( wee k 4 8 ) 
rati o t o baseli ne 
Relati ve c ha n ge i n H D L c h olester ol  
Fr o m ra n d o misati o n ( wee k 3 2 ) t o 
e n d of treat me nt ( wee k 4 8 ) 
rati o t o baseli ne 
Relati ve c ha n ge i n L D L c h olester ol  
Fr o m ra n d o misati o n ( wee k 3 2 ) t o 
e n d of treat me nt ( wee k 4 8 ) 
rati o t o baseli ne 
Relati ve c ha n ge i n V L D L c h olester ol  
Fr o m ra n d o misati o n ( wee k 3 2 ) t o 
e n d of treat me nt ( wee k 4 8 ) 
rati o t o baseli ne 
Relati ve c ha n ge i n Tri gl yceri d es  
Fr o m ra n d o misati o n ( wee k 3 2 ) t o 
e n d of treat me nt ( wee k 4 8 ) 
rati o t o baseli ne 
Relati ve c ha n ge i n Free fatt y a ci ds  
Fr o m ra n d o misati o n ( wee k 3 2 ) t o 
e n d of treat me nt ( wee k 4 8 ) 
rati o t o baseli ne 
 
S u p p orti ve sec o n dar y e n d p oi nts f or N N C 0 1 6 5 -1 8 7 5 1. 0 m g or  2. 0 m g as a n a d d o n t o se ma gl uti de 
2. 4 m g vers us place b o  1. 0 m g or 2. 0 m g  as a n a d d o n t o se ma gl uti de 2. 4 m g:  
E n d p oi nt title  
Ti me fr a me  
U nit  
N u m ber of e mer ge nt a d verse e ve nts 
( T E A Es) 
Fr o m baseli ne at ( wee k 0) t o e n d of 
trial ( wee k 5 6 ) 
C o u nt of e ve nts  
N u m ber of seri o us treat me nt e mer ge nt 
a d verse e ve nts ( S A Es)  
Fr o m baseli ne at ( wee k 0) t o e n d of 
trial ( wee k 5 6 ) 
C o u nt of e ve nts  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 7  of 1 1 6  
 
3. 2. 3  
E x pl or at or y e n d p oi nts  
N ot a p plica ble f or t his trial.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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  Pr ot oc ol  versi o n 4. 0
3 7
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 8  of 1 1 6  
 
4  Tri al desi g n  
4. 1  
O ver all desi g n  
P art 1  
Part 1 is a 1 6 -wee k, f o ur -ar me d, d o u ble -bli n de d ( wit hi n ar ms), ra n d o mise d, place b o -c o ntr olle d, 
si n gle-site trial c o m pari n g c o-escalati o n of t w o d oses of N N C 0 1 6 5 -1 8 7 5 as a n a d d o n t o 
se ma gl uti de s. c. 2. 4 m g v ers us place b o a d de d o n t o se ma gl uti de  s. c. 2. 4 m g i n s u bjects wit h o besit y.  
Part 1 i ncl u des a scree ni n g visit t o assess s u bject’s eli gi bilit y. At visit 2 (ra n d o misati o n) eli gi ble 
s u bjects will e nter a 1 2-wee k d ose escal ati o n peri o d f oll o we d b y a 4 -wee k mai nte na nce p eri o d u ntil 
e n d-of -tr eat me nt. Visits will ta ke place e v er y 2 wee ks. F oll o wi n g eac h d os e escal ati o n, 5 a d diti o nal 
visits will ta ke pla ce c orres p o n di n g t o t he pre dicte d T ma x  of N N C 0 1 6 5 -1 8 7 5. T he f oll o w -u p peri o d 
is 8 wee ks t o acc o u nt f or t he l o n g half-life of N N C 0 1 6 5-1 8 7 5 a n d se ma gl uti de. T o assess s u bject 
safet y d uri n g a n d after w as h-o ut of trial pr o d uct, t w o visits are sc he d ule d 2 wee ks  ( visit 1 6) a n d 
8  wee ks ( visit 1 7) after e n d -of -treat me nt. 
N N C 0 1 6 5 -1 8 7 5/ N N C 0 1 6 5 -1 8 7 5 place b o will be c o -escalate d wit h se ma gl uti de e ver y 2 wee ks f or 
t he first 4 wee ks, a n d e ver y 4 wee ks f or t he ne xt 8 wee ks u ntil fi nal tar get d ose le vels are reac h e d. 
T he s tarti n g d os e of N N C 0 1 6 5-1 8 7 5/ N N C 0 1 6 5 -1 8 7 5 place b o is 0. 0 5 m g or 0. 1 m g a n d t he fi nal 
tar get d ose of N N C 0 1 6 5-1 8 7 5/ N N C 0 1 6 5 -1 8 7 5 place b o is 1. 0 m g or 2. 0 m g, de pe n di n g o n t he 
treat me nt ar m. T h e starti n g d ose s e ma gl uti de is 0. 2 5 m g a n d t he fi nal tar get d ose of se ma gl uti de is 
2. 4 m g i n all ar ms. F urt h er i nf or mati o n o n d ose re gi me ns is pres e nte d i n Secti o n 6. 1 .  
A p pr o xi matel y 2 4 s u bj ects will be ra n d o mise d 2: 1: 2: 1 t o recei ve N N C 0 1 6 5 -1 8 7 5 1. 0 m g  / 
N N C 0 1 6 5 -1 8 7 5 1. 0 m g place b o or N N C 0 1 6 5 -1 8 7 5 2. 0 m g  / N N C 0 1 6 5-1 8 7 5 2. 0 m g place b o i n 
c o m bi nati o n wit h se ma gl uti de. Eac h N N C 0 1 6 5 -1 8 7 5 treat me nt ar m will a d mi nister differe nt d ose 
v ol u mes b ut is bli n de d t o war ds place b o  wit h matc hi n g i njecti o n v ol u mes.  
Part 1 will be c o n d ucte d b y a C R O .  
P art 2  
Part 2 is a 4 8 -wee k, f o ur-ar me d, d o u ble -bli n de d  ( wit hi n ar ms), ra n d o mise d, place b o -c o ntr olle d, 
m ulti -ce ntre, pr o of -of -pri nci ple trial c o m pari n g  o n ce wee kl y N N C 0 1 6 5 -1 8 7 5 as a d d o n t o o nce-
wee kl y se ma gl uti de s.c. 2. 4 m g vers us place b o as a d d o n t o o nce -wee kl y s e ma gl uti de  s.c. 2. 4 m g i n 
s u bjects wit h o besit y. Part 2 will e val uate efficac y a n d safet y f or N N C 0 1 6 5 -1 8 7 5 1. 0  m g, a n d s afet y 
f or N N C 0 1 6 5-1 8 7 5 2. 0 m g.  
Part 2 c o nsists of t w o parts : a n o pe n-la bel r u n-i n part ( Part 2a) w here all s u bjects are tr eate d wit h 
o nce -w ee kl y se ma gl uti de a n d a sec o n d part ( Part 2 b) w here o nce -wee kl y N N C 0 1 6 5 -1 8 7 5 or 
N N C 0 1 6 5 -1 8 7 5 place b o is a d de d t o se ma gl uti de s.c. 2. 4 m g.   
Part 2a i ncl u des a scree ni n g vis it t o assess t he s u bject’s eli gi bilit y. At visit 2 eli gi ble s u bjects will 
e nter a 3 2 -wee k r u n -i n p eri o d wit h 8 wee ks of se ma gl uti de d ose-escalati o n a n d 2 4  wee ks of 
se ma gl uti de s. c. 2. 4 m g mai nte na nce. Se m a gl uti de will be escal ate d e v er y 2 wee ks. Visits wil l ta ke 
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Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
3 9  of 1 1 6  
 
place e v er y 2 w ee ks d uri n g se ma gl uti de d os e escalati o n a n d e ver y 4 wee ks d uri n g se m a gl uti de 
mai nte na nce.  
At  wee k 3 2 , s u bjects w h o ha ve reac h e d t he tar get d ose of se ma gl uti de s.c. 2. 4 m g d uri n g t he r u n -i n 
peri o d a n d f ulfil t he ra n d o misati o n criteria (see Secti o n 5. 5. 2 ) will e nter Part 2 b a n d be ra n d o mise d 
i n a 2: 1 ma n ner t o recei v e eit her o nce-wee kl y N N C 0 1 6 5 -1 8 7 5 1. 0 m g or pl ace b o  1. 0 m g  as a d d-o n 
t o o nce-wee kl y se ma gl uti de 2. 4 m g. Part 2 b i ncl u des 8  wee ks of N N C 0 1 6 5 -1 8 7 5 /place b o  1. 0  m g 
d ose escal ati o n f oll o we d b y 8  w ee ks of N N C 0 1 6 5 -1 8 7 5/ place b o  1. 0  m g mai nte na nce u ntil e n d -of -
treat me nt. I n part 2 b, a s mall c o h ort ( 1 2 s u bjects) will be ran d o mise d 2: 1 t o N N C 0 1 6 5 -1 8 7 5  
2. 0  m g/ place b o  2. 0 m g , t hese s u bjects will ha ve 1 0 wee ks of d os e escalati o n f oll o we d b y 6 wee ks 
o n N N C 0 1 6 5 -1 8 7 5/ place b o 2. 0  m g  mai nte na n ce u ntil e n d -of -treat me nt. F or all gr o u ps, v isits will 
ta ke place e ver y 2 wee ks d uri n g d ose  escalati o n a n d alter nati n g visits/ p h o ne c o ntacts will ta ke place 
e ver y w ee k f or t he re mai ni n g peri o d u ntil e n d -of -treat me nt. A f oll o w -u p visit (‘e n d of trial visit’) 
f or safet y assess me nts is sc he d ule d 8 wee ks after e n d of treat me nt t o acc o u nt f or t he l o ng h alf -life 
of N N C 0 1 6 5 -1 8 7 5 a n d s e ma gl uti de. I nf or mati o n o n d ose re gi me ns is pres e nte d i n Ta ble  6 -2 , 
Ta ble  6 -3 , Ta bl e  6 -4 , Ta ble  6 -5 . 
T he trial d urati o n of Part 2 will be a p pr o xi matel y 5 8  wee ks ; 2 wee ks of scree ni n g, 3 2  wee ks of 
se ma gl uti de r u n-i n, 1 6 w ee ks of N N C 0 1 6 5-1 8 7 5 or N N C 0 1 6 5 -1 8 7 5 place b o a d d o n t o se ma gl uti de 
s.c. 2. 4 m g. T h e f oll o w -u p is 8 wee ks.  
Ni net y  s u bjects are pl a n n e d t o  be e nr olle d i n Part 2a t o e ns ure a p pr o xi matel y 7 5  s u bjects eli gi ble 
f or ra n d o misati o n i n Part 2 b. 
A n o ver vie w of t he trial desi g n f or Part 1 a n d Part 2 is prese nte d i n  Fi g ure  4 -1 . 
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Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 0  of 1 1 6  
 
Fi g ure  4 -1  
O ver vie w of t he tri al desi g n  
 
I n Part 1, acc or di n g t o ‘t he i nter nal N o v o N or dis k safet y o versi g ht gr o u p c harter’, a bli n de d i nter nal 
N o v o N or dis k safet y o v ersi g ht gr o u p will m o nit or t he trial c o nti n u o usl y f or safet y, t olera bilit y a n d 
P K pr o perties o n  t he i n di vi d ual s u bject le vel a n d d ose gr o u p le vel. F oll o wi n g L P L V i n Part 1, t he 
i nter nal N o v o N or dis k safet y o v ersi g ht gr o u p will e val uate t he t otalit y, patt er n a n d se v erit y of 
o bser ve d A Es, la b orat or y para meters a n d P K pr o p ert ies of N N C 0 1 6 5-1 8 7 5 base d o n u n bli n de d 
data.  
Part 1 a n d Part 2a will be c o n d ucte d i n se mi-parall el, as t he recr uit me nt f or t he t w o parts will be 
se parat e d i n ti me all o wi n g f or a c o n cl usi o n t o be ma de o n Part 1 bef ore s u bjects fr o m Part  2a are 
ra n d o mise d int o Part 2 b. T he decisi o n t o pr o gress i nt o Part 2 b will be ta ke n b y t he N o v o  N or dis k 
safet y c o m mittee bas e d o n a rec o m me n d ati o n fr o m t he N o v o N or dis k safet y o versi g ht gr o u p. T h e 
safet y c o m mittee ma y deci de w het her: 
•  t he trial s h o ul d pr ocee d i nt o Part 2 b 
•  t he Part 2 b pr ot oc ol s pecifie d fre q u e nc y of visits a n d/ or cli nical a n d la b orat or y m o nit ori n g 
s h o ul d be a dj uste d 
•  t he Part 2 b pr ot oc ol s pecifie d d ose escalati o n s h o ul d be a dj uste d a n d/ or t he o nce wee kl y tar get 
d ose of 2 m g of N N C 0 1 6 5 -1 8 7 5 s h o ul d be re d u ce d  
If c ha n ges t o t he pr ot oc ol f or Part 2 b are re q uire d base d o n t he o utc o me of Part 1, a n d if t he 
pr ot oc ol a me n d me nt is n ot fi nalise d bef ore t he first s u bjects i n Part 2a reac h t he ra n d o misati o n 
visit ( V 1 0) at wee k 2 4, s u bjects are all o we d t o c o nti n ue i n Part  2a o n o nce -wee kl y se m a gl uti de s.c. 
2. 4 m g u ntil ra n d o misati o n ca n be i nitiate d. T he ma xi m u m all o we d a d diti o nal ti me i n Part 2a is 
8  wee ks w h ere a d diti o nal visits ( V 9. 1 a n d V 9. 2) will ta ke place a p pr o xi matel y e ver y 4 wee ks.  
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Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 1  of 1 1 6  
 
If t he ma xi m u m all o we d a d diti o nal ti me i n Part 2a is use d, t he trial d urati o n of Part 2 will be 
a p pr o xi matel y 5 8 wee ks ( 2 wee ks of scree ni n g, 3 2 wee ks of s e ma gl uti de r u n -i n, 1 6 wee ks of 
N N C 0 1 6 5 -1 8 7 5 2. 4 m g/ N N C 0 1 6 5 -1 8 7 5 place b o a d d o n t o se ma gl uti de  s.c. 2. 4 m g a n d 8 wee ks of 
f oll o w-u p).   
I n pr ot oc ol versi o n 4. 0, t he t w o a d diti o nal r u n-i n visits ( V 9. 1 a n d V 9. 2) ha ve bee n acti vate d.  
4. 2  
Scie ntific r ati o n ale f or tri al desi g n  
T he trial desi g n i n Part 1 will all o w f or t he e val u ati o n of safet y, t olera bilit y a n d P K pr o perties of 
t w o differe nt d os e le vels of o nce-wee kl y N N C 0 1 6 5 -1 8 7 5 c o -es calate d i n c o m bi nati o n wit h o nce -
wee kl y se ma gl uti de. T h e visit str uct ure will all o w f or fre q ue nt i nteracti o n bet wee n s u bject a n d 
i n vesti gat or h ere b y e ns uri n g m o nit ori n g of s u bject safet y, A E ha n dli n g a n d re p orti n g.   
T he trial desi g n i n Part 2 will all o w f or t he c o m paris o n of o nce -wee kl y N N C 0 1 6 5 -1 8 7 5 1 .0  m g 
vers us place b o 1. 0 m g as a d d o n t o o nce -wee kl y s e ma gl uti de s.c. 2. 4 m g. T he 3 2 -wee k r u n -i n 
peri o d ( Part  2a) of t he tri al all o ws f or wei g ht l oss t o be o btai ne d wit h se ma gl uti de s.c. 2. 4 m g 
bef ore t h e a d d  o n of N N C 0 1 6 5 -1 8 7 5 1 . 0 m g. T he desi g n all o ws f or i de ntif yi n g a n y a d diti o nal 
wei g ht l oss b y t he c o m bi nati o n treat me nt c o m pare d t o t he effect of c o nti n ui n g wit h se ma gl uti de s.c. 
2. 4 m g treat me nt.  F urt h er m ore, t he trial desi g n will all o w f or e val uati o n  of safet y, t olera bilit y a n d 
P K pr o perties  i n t he N N 0 1 6 5-1 8 7 5 2. 0 m g d ose  gr o u p . 
A treat me nt d ur ati o n of 1 6 wee ks ( Part 2 b) is c o nsi dere d a p pr o priate t o e v al uate pro of -of -pri nci ple 
f or o nce-wee kl y N N C 0 1 6 5 -1 8 7 5 f or w ei g ht l oss effects a n d will pr o vi de i nf or mati o n o n t he safet y 
a n d t olera bilit y pr ofile of N N C 0 1 6 5 -1 8 7 5 .  
4. 2. 1  
S u bject i n p ut i nt o desi g n  
T here h as bee n n o i nteracti o n wit h s u bjects f or i n p ut t o desi g n of t he c urre nt trial; h o we ver, 
e x perie nce fr o m pre vi o us o besit y trials has b ee n i m ple me nte d t o t he e xte nt p ossi ble.  
4. 3  
J ustific ati o n f or d ose  
N N C 0 1 6 5 -1 8 7 5  
T he d ose le vels of 1. 0 a n d 2. 0 m g of N N C 0 1 6 5 -1 8 7 5 ha ve bee n select e d b ase d o n cli nical a n d 
n o n -cli nical fi n di n gs.  
I n tri al N N 9 7 7 5-4 3 9 8, t h e safet y, t olera bilit y, a n d P K/ P D pr o perties of a si n gle s.c d ose of 
N N C 0 1 6 5 -1 8 7 5 were teste d. Si n gle s.c d ose of N N C 0 1 6 5-1 8 7 5 u p t o 2. 1 m g as m o n ot hera p y, a n d 
si n gle s.c d os e of N N C 0 1 6 5-1 8 7 5 u p t o 1. 7 m g i n c o m bi nati o n wit h se ma gl u ti de 0. 2 5 m g was 
s h o w n t o be safe a n d t olera ble. Base d o n d ata fr o m N N 9 7 7 5-4 3 9 8, t he half -life of N N C 0 1 6 5-1 8 7 5 
is esti mate d t o be a p pr o xi matel y 1 0 da ys, s u p p orti n g o nce-wee kl y d osi n g.  
I n p art 1 of t his trial ( N N 9 7 7 5-4 7 0 8), safet y, t olera bilit y a n d P K pr o pe rties were t o be e x pl ore d f or 
b ot h 1. 0 m g a n d 2. 0 m g N N C 0 1 6 5 -1 8 7 5/ place b o. H o we ver, data f or t he 2. 0 m g d ose of N N C 0 1 6 5 -
1 8 7 5 were n ot a vaila ble fr o m part 1 of t he trial, d u e t o treat me nt disc o nti n uati o n attri b ute d t o 
t olera bilit y iss ues wit h t he d ose escalati o n re gi me n use d i n part 1. T he l o w er starti n g d ose a n d t h e 
d ose escal ati o n re gi me n use d f or t he 1. 0 m g N N C 0 1 6 5 -1 8 7 5 d ose gr o u p a p peare d t olera ble. Bas e d 
N N 9 7 7 5- 4 7 0 8
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Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 2  of 1 1 6  
 
o n part 1, t he f oll o wi n g c ha n ges are ma de f or part 2 b i n Pr ot oc ol versi o n 4. 0: t he N o v o N or dis k 
Safe t y C o m mittee has d eci de d t o u p date part 2 b b y l o weri n g t he starti n g d ose t o 0. 0 5 m g 
N N C 0 1 6 5 -1 8 7 5/ place b o, b y a d di n g e xtra ste ps i n t he d ose escalati o n re gi m e n a n d b y c h a n gi n g t h e 
mai nte na nce d os e t o 1. 0 m g N N C 0 1 6 5 -1 8 7 5/ place b o. I n a d diti o n, t w o e xtra treat me nt ar ms ha ve 
bee n a d d e d f or safet y e v al uati o n of t he 2. 0 m g d os e of N N C 0 1 6 5 -1 8 7 5, i n w hic h 1 2 s u bjects will be 
ra n d o mise d 2: 1 t o 2. 0 m g N N C 0 1 6 5-1 8 7 5/ place b o.  
T he e x p os ure li mits are base d o n t he e x p os ures o bser ve d at t he N O A E L n o n -cli nical t o xicit y st u d y, 
a n d t he ma xi m u m d ose of N N C 0 1 6 5 -1 8 7 5 2. 0 m g is selecte d i n or der n ot t o e xcee d t his. Please 
refer t o t he I n vesti gat or’s Br oc h ure N N C 0 1 6 5-1 8 7 5 a n d a n y u p dates h ere of 3 6. 
Se m a gl uti de  
I n a p hase 3 a trial ( N N 9 5 3 6-4 3 7 3; S T E P 1) c o m prisi n g 1, 9 6 1 a d ults wit h o besit y or o ver wei g ht wit h 
co m or bi dities, s u bjects treate d wit h se ma gl uti de s. c. 2. 4 m g ac hie ve d a mea n wei g ht l oss of 1 4. 9 %, 
fr o m a baseli ne b o d y wei g ht of 1 0 5. 3 k g, c o m pare d t o a 2. 4 % wei g ht l oss wit h place b o. I n a d diti o n, 
8 6. 4 % of t h ose w h o recei ve d se ma gl uti de 2. 4 m g s.c. reac he d  a wei g ht l oss of 5 % or m ore after 6 8 
wee ks, c o m pare d t o 3 1. 5 % wit h place b o.  Se ma gl uti de  2. 4 m g  s.c. a p p eare d t o ha ve a safe a n d well 
t olerate d pr ofile i n li ne wit h w hat has pre vi o usl y b ee n o bser ve d f or s e ma gl uti de 6 2. T he m ost 
c o m m o n a d verse e ve nts a m o n g s u bje cts treate d wit h  se ma gl uti de 2. 4  m g  s. c. were gastr oi ntesti nal 
e ve nts. M ost e ve nts were tra nsie nt, a n d mil d or m o derate i n se v erit y.  
I n N N 9 7 7 5 -4 7 0 8  Part 1, se ma gl uti de d osi n g will be i nitiate d at a o nce -wee kl y d ose of 0. 2 5 m g a n d 
i ncreas e d t o 0. 5 m g a nd 1. 0 m g aft er 2 wee ks. At 1. 0 m g, d ose escalati o n will occ ur e ver y 4 wee ks 
t o d oses of 1. 7 a n d 2. 4 m g/ wee k u ntil t he tar get d ose is reac h e d after a t otal of 1 6 wee ks. Fe wer 
e x pecte d t olera bilit y iss u es at l o wer d ose le vels all o w f or faster d ose es calati o n  at l o wer d oses 
c o m pare d t o hi g her d oses.  
I n N N 9 7 7 5 -4 7 0 8  Part 2 a, se ma gl uti de d osi n g will be i nitiate d at a o nce -wee kl y d ose of 0. 2 5 m g a n d 
f oll o we d b y d ose i ncreas es e ver y 2 wee ks (t o d oses of 0. 5, 1. 0, 1. 7 a n d 2. 4 m g/ wee k), u ntil t he 
tar get d ose is reac h e d aft er 8 wee ks. T he s u bjects will c o nti n ue at se ma gl uti de 2. 4 m g o nce-wee kl y  
f or t he re m ai ni n g p art of t he trial ( u ntil wee k 4 8 ). 
It is well k n o w n t hat t o miti gate gastr oi ntesti nal si de effects wit h G L P-1 R A treat me nt, d ose 
escalati o n t o t he tar get d ose is re q uire d.  
4. 4  
E n d of tri al defi niti o n  
A s u bject is c o nsi dere d t o ha ve c o m plete d t h e trial if he/s he has c o m plete d eit her Part 1 or Part 2 b 
of t he trial i ncl u di n g t he l ast visit i n Part 1 or Part 2 b.  T he e n d of t he tri al is defi ne d as t he d ate of 
t he last visit of t he last s u bject i n Part 2 b. 
N N 9 7 7 5- 4 7 0 8
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Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 3  of 1 1 6  
 
5  Tri al p o p ul ati o n  
Pr os pecti ve a p pr o val of pr ot oc ol de viati o ns t o recr uit me nt a n d e nr ol me nt criteria, als o k n o w n as 
pr ot oc ol wai vers or e x e m pti o ns, is n ot per mitte d. T he i ncl usi o n a n d e x cl usi o n criteria liste d bel o w 
a p pl y f or b ot h Part 1 a n d Part 2 . 
5. 1  
I ncl usi o n criteri a 
S u bjec ts are eli gi ble t o b e i ncl u de d i n t he trial o nl y if all of t h e f oll o wi n g criteria a p pl y: 
1.  I nf or me d c o ns e nt o btai ne d bef ore a n y trial-relate d acti vities. Trial-rel ate d acti vities are a n y 
pr oce d ures t hat are carrie d o ut as part of t he trial, i ncl u di n g acti vit ies t o deter mi ne s uita bilit y f or 
t he trial. 
2.  Male or fe m ale, a ge a b o v e or e q ual t o 1 8 years  at t he ti me of si g ni n g i nf or m e d c o nse nt.  
3.  B MI 3 0. 0 –  4 5. 0 k g/ m 2 ( b ot h i ncl usi ve) at t he scree ni n g visit. 
5. 2  
E xcl usi o n criteri a  
S u bjects are e x cl u de d fr o m t he trial if a n y of t he f oll o wi n g criteria a p pl y:  
Gl yc ae mi a -rel ate d  
1.  H b A 1 c ≥ 4 8 m m ol/ m ol ( 6. 5 %) as meas ure d b y a ce ntral la b orat or y at scree ni n g.  
2.  Hist or y of t y p e 1 or t y pe 2 dia betes mellit us.  
3.  Treat me nt wit h gl uc ose -l o weri n g a ge nt(s) wit hi n 9 0 da ys b ef ore scree ni n g. 
O be sit y-rel ate d  
4.  A self -re p orte d c h a n ge i n b o d y w ei g ht > 5 k g ( 1 1 l bs) wit hi n 9 0 da ys b ef ore scree ni n g 
irres pecti ve of me dical rec or ds. 
5.  Treat me nt wit h a n y me di cati o n i n dicate d f or wei g ht ma na ge me nt wit hi n 9 0 da ys b ef ore 
scree ni n g. 
6.  Pre vi o us or pla n ne d ( d uri n g t he trial p eri o d) o besit y treat me nt wit h s ur ger y or a wei g ht l oss 
de vice. H o we ver, t h e f oll o wi n g are all o we d: ( 1) li p os ucti o n a n d/ or a b d o mi n o plast y, if 
perf or me d > 1 year bef ore scree ni n g, ( 2) la par osc o pic ba n di n g, if t h e ba n d has bee n re m o ve d 
> 1  year bef ore  scree ni n g, ( 3) i ntra gastric ball o o n, if t he ball o o n has bee n re m o ve d > 1 year 
bef ore s cree ni n g or ( 4) d u o de nal -jej u nal b y pass sl ee ve, if t he sl ee ve h as bee n re m o ve d > 1 year 
bef ore s cree ni n g.  
7.  U nc o ntr olle d t h yr oi d disease per i n vesti gat ors dis creti o n.  
8.  Treat m e nt wit h a G L P -1 R A wit hi n 1 8 0 da ys bef ore scree ni n g.  
Me nt al he alt h -rel at e d  
9.  Hist or y of m aj or de pressi ve dis or der wit hi n 2 years bef ore s cree ni n g.  
1 0.  Hist or y of ot h er se v ere ps yc hiatric dis or ders (e. g. , sc hiz o p hre nia or bi p olar dis or der). 
1 1.  A lifeti me hist or y of  a s uici dal atte m pt.  
1 2.  S uici dal be ha vi o ur wit hi n 3 0 da ys b ef ore scree ni n g  
1 3.  S uici dal i deati o n c orres p o n di n g t o t y p e 4 or 5 o n t he C ol u m bia -S uici de Se verit y Rati n g Scal e 
( C-S S R S) wit hi n t he past 3 0 da ys b ef ore scree ni n g  
1 4.  A Patie nt Healt h Q uesti o n naire -9 ( P H Q -9) sc ore ≥ 1 5 at scree ni n g 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
4 3
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 4  of 1 1 6  
 
C ar di o v asc ul ar assess me nts  
1 5.  Sitti n g bl o o d press ure o utsi de t he ra n ge of 9 0 -1 5 9 m m H g f or s yst olic or 5 0 -9 9 m m H g f or 
diast olic at scree ni n g.  
1 6.  P ulse of ≥ 1 0 0 beats/ mi n at scree ni n g.  
1 7.  Prese nce or hist or y of car di o vasc ular diseas e, i ncl u di n g m y ocar dial i nfarcti o n, str o ke, sta ble or 
u nsta ble a n gi na pect oris, tra nsie nt isc hae mic attac k, car diac dec o m p e nsati o n, cli nicall y 
si g nifica nt arr h yt h mias or cli nicall y si g nifica nt c o n d ucti o n dis or ders.  
1 8.  S u bject prese ntl y classifi e d as bei n g i n Ne w Y or k H eart Ass o ciati o n ( N Y H A) Class I V heart 
fail ure. 
Ge ner al s af et y  
1 9.  Prese nce or hist or y of pr ostate disease  
2 0.  Pr ostate S pecific A nti ge n > 4 n g/ m L as m eas ure d b y t he ce ntral la b orat or y at scree ni n g  
2 1.  Re nal i m pair me nt meas ure d as esti mate d Gl o mer ular Filtrati o n Rate (e G F R) val ue of < 6 0 
ml/ mi n/ 1. 7 3 m 2 as defi ne d b y K DI G O 2 0 1 2 3 9 b y t he ce ntral la b orat or y at scree ni n g.  
2 2.  I m paire d li ver f u ncti o n, defi ne d as Al a ni ne A mi n otra nsferase ( A L T) ≥2. 5 ti mes or As partate 
A mi n otra nsferase ( A S T) ≥2. 5 ti mes or Al kali ne P h os p hatase ≥2. 5 ti mes or Bilir u bi n > 1. 5 ti mes 
u p per n or mal li mit  ( U N L), as meas ure d b y t he ce ntral la b orat or y at scree ni n g. 
2 3.  K n o w n or s us pect e d a b use of alc o h ol or recreati o nal dr u gs.  
2 4.  Pers o nal or first -d e gree relati ve(s) hist or y of m ulti ple e n d ocri ne n e o plasia t y p e 2 or me d ullar y 
t h yr oi d carci n o ma. 
2 5.  Prese nce or hist or y of c hr o nic pa ncreatitis.  
2 6.  Prese nce of ac ut e pa ncreatitis wit hi n 1 8 0 da ys pri or t o t he first scree ni n g visit.  
2 7.  Prese nce or hist or y of mali g na nt ne o plas ms wit hi n t he past 5 years pri or t o scree ni n g. Bas al a n d 
s q ua m o us cell s ki n ca ncer a n d a n y carci n o ma i n-sit u are all o we d. 
2 8.  S ur ger y sc he d ul e d d uri n g t he d urati o n of t he trial, e x ce pt f or mi n or s ur gical pr oce d ures, per 
i n vesti gat or discreti o n. 
2 9.  Partici pati o n i n a n y cli nical trial of a n a p pr o ve d or n o n -a p pr o ve d i n vesti gati o nal me dici nal 
pr o d uct wit hi n 9 0 da ys b ef ore s cree ni n g.  
3 0.  K n o w n or s us pect e d h y p erse nsiti vit y t o trial pr o d ucts or relate d pr o d ucts.  
3 1.  Pre vi o us partici pati o n i n t his trial. Partici pati o n is defi ne d as si g ne d i nf or me d c o nse nt.  
3 2.  Ot her s u bject(s) fr o m t he sa me h o use h ol d partici p ati n g i n a n y trial testi n g N N C 0 1 6 5 -1 8 7 5 or 
se ma gl uti de. 
3 3.  Fe male w h o is pre g na nt, breast -fee di n g or i nte n ds t o bec o me pre g n a nt or is of c hil d-beari n g 
p ote ntial a n d n ot usi n g a hi g hl y effecti ve c o ntrac e pti ve met h o d (see A p pe n di x 4, Secti o n 1 0. 4 ) 
3 4.  C O VI D -1 9 vacci n ati o ns wit hi n  3 0 da ys bef ore  s cree ni n g. 
3 5.  A n y dis or d er, u n willi n g n ess or i na bilit y, n ot c o vere d b y a n y of t he ot her e x cl usi o n criteria, 
w hic h i n t he i n vesti gat or’s o pi ni o n mi g ht je o par dise s u bject’s safet y or c o m plia nce wit h t he 
pr ot oc ol.  
5. 3  
Lif est yle c o nsi der ati o ns  
T o e ns ure ali g n me nt re gar di n g perf or m a nce of ass ess me nts acr oss s u bjects a n d trial sites, t he bel o w 
restricti o ns a p pl y. 
5. 3. 1  
Me als a n d diet ar y rest ricti o ns  
•  S u bjects m ust atte n d visits fasti n g acc or di n g t o t h e fl o wc hart ( Secti o n 1. 2 ). 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
4 4
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 5  of 1 1 6  
 
•  Fasti n g is defi ne d as:  
•  n o f o o d or li q ui d, e x ce pt f or water, f or at least 8 h o urs pri or t o t he visit.  
•  n o water 2 h o urs pri or t o t he visit.  
•  If t he s u bject is n ot fasti n g as re q uire d, t h e s u bject m ust be calle d i n f or a n e w visit wit hi n t he 
visit wi n d o w t o ha ve t he fasti n g pr oce d ures perf or me d.  
•  Pr oce d ures re q uiri n g t he s u bject t o fast i ncl u de bl o o d sa m pli n g of F P G, fasti n g ser u m i ns uli n 
a n d free fatt y aci ds.  
5. 3. 2  
C affei ne, alc o h ol a n d t o b acc o  
•  T o bac c o us e is defi ne d as s m o ki n g at least o ne ci garette or e q ui vale nt dail y.  
•  S u bject s h o ul d a v oi d caffei ne a n d s m o ki n g at least 3 0 mi n utes pri or t o meas ure me nt of bl o o d 
press ure.  
5. 3. 3  
P h ysic al acti vit y  
N ot a p plica ble f or t his trial.  
5. 4  
Scree n f ail ures  
Scree n fail ures are defi ne d as s u bjects w h o c o nse nt t o partici pate i n t he cli nical trial b ut are n ot 
eli gi ble f or partici pati o n acc or di n g t o i ncl usi o n/e xcl usi o n criteria. A mi ni mal set of scree n fail ure 
i nf or mati o n is re q uire d t o e ns ure tra ns p are nt re p orti n g of scree n fail ur e s u bjects t o meet 
re q uire me nts fr o m re g ulat or y a ut h orities. Mi ni mal i nf or mati o n i ncl u des i nf or me d c o nse nt dat e, 
de m o gra p h y, scree n fail ure details, eli gi bilit y criteria, a n d a n y s eri o us a d verse e ve nt ( S A E).  
O nl y Part 2 of t h e trial will be ha n dle d b y I W R S.  
A scree n fail ure sessi o n m ust be ma de i n t he i nteracti ve we b res p o nse s yst e m (I W R S) f or Part 2 . 
F or Part 1 t he  s cree n fail ure reas o n m ust be e ntere d i n t he e C R F e n d of trial f or m.   
I n di vi d uals w h o d o n ot meet t he criteri a f or p arti ci pati o n i n t his trial ma y n ot be rescree n e d. If t he 
s u bject has faile d o n e of t he i ncl usi o n criteria or f ulfille d o ne of t he e x cl usi o n criteria relate d t o 
la b orat or y para meters, re-sa m pli n g is n ot all o we d. H o we ver, i n case of tec h nical iss ues (e. g. , 
hae m ol ys e d or l ost), re -s a m pli n g is all o we d f or t he affecte d para m eters. 
H o we ver, if a s u bject is i na d verte ntl y ra n d o mise d i n vi olati o n of t he i ncl usi o n a n d e x cl usi o n criteria 
( R VI E) t he f oll o wi n g pr oce d ure m ust be p erf or me d:  
•  Te m p orar y disc o nti n uati o n of ra n d o mise d treat me nt  
•  Safet y ris k e val uati o n b y t he pri nci pal i n vesti gat or a n d t he me dical r es p o nsi ble fr o m 
N o v o  N or dis k A/ S t o deter mi ne w het her ra n d o mis e d treat me nt s h o ul d be restarte d or 
per ma ne ntl y disc o nti n ue d (a treat me nt disc o nti n uati o n sessi o n ma de i n I W R S)  
•  S u b missi o n of a n i m p orta nt pr ot oc ol de viati o n a n d n otificati o n of t he I E C/I R B a n d re g ulat or y 
a ut h orities acc or di n g t o l ocal re q uir e me nts.  
5. 5  
R u n -i n criteri a a n d/ or r a n d o mis ati o n criteri a  
First d ose m ust o n l y be a d mi nistere d after assess me nts relate d t o pri mar y a n d/ or sec o n d ar y 
e n d p oi nts are c o m plet e d.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
4 5
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 6  of 1 1 6  
 
Re -sa m pli n g is n ot all o w e d if t he s u bject has faile d a n y of t he r u n-i n/ra n d o misati o n criteria relat e d 
t o la b orat or y para meters. H o we ver, i n case of tec h nical iss ues (e. g., hae m ol ys e d or l ost), 
re-sa m pli n g is all o we d f or t he affecte d para meters. 
5. 5. 1  
R u n -i n criteri a 
P art 2 a  
T o be eli gi ble t o e nter r u n -i n, all r u n-i n criteri a m ust be a ns were d “ yes ” 
1.  A P H Q -9 sc ore of < 1 5 at wee k 0  
2.  N o s uici dal be ha vi o ur i n t he peri o d bet wee n scree ni n g a n d wee k 0  
3.  N o s uici dal i deati o n c orres p o n di n g t o t y pe 4 or 5 o n t he C -S S R S i n t he peri o d bet wee n 
scree ni n g a n d wee k 0 
5. 5. 2  
R a n d o mis ati o n criteri a  
P art 1  
T o be ra n d o mise d, all ra n d o misati o n criteria m ust be a ns were d “ yes ” 
1.  A P H Q -9 sc ore of < 1 5 at wee k 0  
2.  N o s uici dal be ha vi o ur i n t he peri o d bet wee n scree ni n g a n d wee k 0  
3.  N o s uici dal i deati o n c orres p o n di n g t o t y pe 4 or 5 o n t he C -S S R S i n t he peri o d bet wee n 
scree ni n g a n d wee k 0 
P art 2 b  
T o be ra n d o mise d, all ra n d o misati o n criteria m ust be a ns were d “ yes” 
1.  Atte n d t he ra n d o misati o n visit ( wee k 3 2 ) 
2.  Ha ve es calate d t o t he t ar get d ose wit h se ma gl uti de s.c. 2. 4 m g b y wee k 2 8  
3.  Are at tar get d ose at t he ra n d o misati o n visit ( wee k 3 2 ) 
 
S u bject n ot f ulfilli n g t he ra n d o misati o n criteria will be c o nsi dere d r u n -i n fail ure. All r u n -i n fail ures 
s h o ul d atte n d t he ‘e n d of trial’ visit 8 wee ks + 5 da ys after t heir wee k 3 2  visit.  
5. 5. 3  
D osi n g d a y criteri a  
N ot a p plica ble f or t his trial.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
 .
-
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1
 |
 of
  Pr ot oc ol  versi o n 4. 0
4 6
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 7  of 1 1 6  
 
6  Tre at me nts  
6. 1  
Tre at me nts a d mi nistere d  
I n vesti g ati o n al me dici n al pr o d ucts (I M P) 
All trial pr o d ucts liste d i n Ta ble  6 -1  are c o nsi d ere d I M Ps a n d are s u p plie d b y N o v o N or dis k.  
T a ble  6 -1  
I n vesti g ati o n al me dici n al pr o d ucts pr o vi de d b y N o v o N or dis k  
Tri al pr o d uct 
n a me:  
 
N N C 0 1 6 5 -1 8 7 5 A 
0. 2  m g/ ml   
N N C 0 1 6 5 -1 8 7 5 A 
5. 0  m g/ ml  
Se ma gl uti de B  
3. 0 m g/ ml  
N N C 0 1 6 5 -1 8 7 5 
Place b o A  
D os a ge f or m  
S ol uti o n f or 
i nj ecti o n 
S ol uti o n f or i nj ecti o n  
S ol uti o n f or 
i nj ecti o n 
S ol uti o n f or 
i nj ecti o n 
R o ute of 
a d mi nistr ati o n  
S u bc uta ne o us  
S u bc uta ne o us  
S u bc uta n o us  
S u bc uta n o us  
D osi n g 
i nstr ucti o ns 
O nce -wee kl y  
O nce -wee kl y  
O nce -wee kl y  
O nce -wee kl y  
P ac k a gi n g  
 
3 ml cartri d ge f or 
use i n N o v o P e n ®  4 
( d ura ble de vice) 
3 ml cartri d ge f or use i n 
N o v o P e n ®  4 ( d ura ble 
de vice)  
P D S 2 9 0 pe n i nj ect or 
t o be use d is wit h a 
U 1 0 0 scale o n t he 
scale dr u m  
3 ml cartri d ge f or 
use i n N o v o P e n ® 4 
( d ura ble de vice) 
 
•  Se ma gl uti de will be a d mi nistere d as o pe n -l a bel, w hile N N C 0 1 6 5-1 8 7 5 is bli n de d b y 
c orres p o n di n g pla ce b o.  
•  D osi n g m ust be a d mi nistere d o n site at all site visits, f or b ot h Part 1 a n d Part 2. O n site t he d ose 
s h o ul d be a d mi nistere d b y t he i n vesti gat or or dele gat e d staff. T h e i n vesti gat or m ust d oc u me nt 
t hat directi o ns f or use ( D F U) are gi ve n t o t he s u bj ect ver b all y a n d i n writi n g  
•  F or t he d osi n g at h o me, s u bjects will be i nstr u cte d t o i nject trial pr o d ucts o nce  wee kl y o n t he 
sa me da y of t he wee k (t o t he e xte nt p ossi ble) t hr o u g h o ut t he trial.  
•  I n Part 1 a n d 2 b all s u bjects will be i nstr ucte d t o i nject t w o i njecti o ns (at t he sa me ti me) eac h 
wee k; o ne d os e of se ma gl uti de a n d o ne d os e N N C 0 1 6 5 -1 8 7 5/ place b o.  
•  I n Part 2a, all s u bjects will be i nstr ucte d t o i nject o ne i njecti o n wit h se ma gl uti de eac h wee k. 
•  Trial pr o d ucts c a n be ta k e n at a n y ti me of da y, irres pecti ve of ti mi n g of meals.  
•  Trial pr o d uct i njecti o ns s h o ul d be a d mi nistere d s u bc ut a ne o usl y i n t he t hi g h or a b d o me n  
•  T he a d mi nistrati o n of N N C 0 1 6 5 -1 8 7 5/ place b o m ust al wa ys b e i n t he ri g ht si de of t he a b d o me n 
or t he ri g ht t hi g h. 
•  T he a d mi nistrati o n of se ma gl uti de m ust al wa ys b e i n t he left si de of t he a b d o me n or t he left 
t hi g h.  
•  D osi n g i nf or m ati o n m ust be c ollecte d i n t he desi g nate d pa per d osi n g di ar y, e ntries m ust be 
e ntere d i n t he case re p ort f or m ( C R F) a n d c o ntai ns:  
•  Date  
•  Ti me of d ose  
•  Val ue s h o w n i n d ose c o u nter or n ot ta ke n  
•  I nje cti o n site:  
▪ t hi g h or a b d o me n  
•  I nje cti o n si de 
▪ left or ri g ht   
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
4 7
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 8  of 1 1 6  
 
•  D ose Val ue e ntere d b y site staff  
•  If a sc h e d ule d d ose of a n y trial pr o d u ct is misse d, it s h o ul d be a d mi nistere d as s o o n as n otice d, 
pr o vi de d t he ti me t o t he ne xt sc he d ule d d ose is at least 2 da ys ( 4 8 h o urs). If a d ose is misse d a n d 
t he ne xt sc he d ule d d ose is less t ha n 2 da ys ( 4 8 h o urs) a wa y, t he s u bject s h o ul d n ot a d mi nister a 
d ose u ntil t he ne xt sc he d ule d d ose. A misse d d ose s h o ul d n ot affect t he s c h e d ule d d osi n g d a y of 
t he wee k. T h e sc he d ul e d d osi n g da y of t h e wee k s h o ul d re mai n t he sa me t hr o u g h o ut t he tri al if 
p ossi ble.  
•  If ≥ 2 c o nsec uti ve d oses of trial pr o d uct are misse d, t he s u bject s h o ul d be e nc o ura ge d t o 
rec o m me nce t he treat me nt, if c o nsi dere d safe as p er t he i n vesti gat or’s discreti o n a n d if t he 
s u bject d oes n ot meet a n y of t he dis c o ntin uati o n criteria ( Secti o n 7. 1 ). T h e trial pr o d uct s h o ul d 
be c o nti n ue d as s o o n as t he sit uati o n all o ws. T he misse d d oses s h o ul d n ot affect t he sc he d ul e d 
d osi n g da y of t h e wee k. T he start d ose f or re -i nitiati o n of trial pr o d uct is at t he i n vesti gat or’s 
discreti o n. I n cas e of q uesti o ns relate d t o re -i nitiati o n of trial pr o d uct, t he i n vesti gat or s h o ul d 
c o ns ult N o v o N or dis k gl o bal me dical e x perts.  
•  T o pre ve nt  pe n mi x -u p a n d me dicati o n err ors, T he Pe n Differe ntiati o n G ui de m ust be use d 
d uri n g tr ai ni n g of site staff a n d s u bjects a n d ha n de d o ut t o s u bjects w he n a d mi nisteri n g trial 
pr o d ucts at h o me  ( please see Pe n Differe n ce G ui d a nce ) 
T a ble  6 -2  
P art 1. D osi n g det ails f or N N C 0 1 6 5 -1 8 7 5 a n d c orres p o n di n g pl ace b o ar ms 
d uri n g t he esc al ati o n a n d m ai nte n a nce p h ases usi n g t he N o v o Pe n ® 4  
T ar g et 
d ose  
U nit  
Visit 2  
R a n d o mis ati o n  
Visit 4  
Wee k 2  
Visit 6  
Wee k 4  
Visit 9  
Wee k 8  
Visit  1 2  
Wee k 1 2  
& u ntil E n d of 
tre at me nt 
1. 0 m g   D ose i n m g  
0. 0 5  
0. 1  
0. 2 5  
0. 5  
1. 0  
Pr o d uct Stre n gt h  i n m g/ ml 
0. 2  
0. 2  
5. 0  
5. 0  
5. 0  
V ol u me i n m L  
0. 2 5  
0. 5  
0. 0 5  
0. 1  
0. 2  
V al ue s h o w n i n d ose c o u nter  
2 5  
5 0  
5  
1 0  
2 0  
2. 0 m g   D ose i n m g  
0. 1  
0. 2 5  
0. 5  
1. 0  
2. 0  
Pr o d uct Stre n gt h  i n m g/ ml 
0. 2  
5. 0  
5. 0  
5. 0  
5. 0  
V ol u me i n m L  
0. 5  
0. 0 5  
0. 1  
0. 2  
0. 4  
V al ue s h o w n i n d ose c o u nter  
5 0  
5  
1 0  
2 0  
4 0  
 
T a ble  6 -3  
P art 1. D osi n g det ails f or se m a gl uti de B 3. 0 m g/ m L P D S 2 9 0 d uri n g t he 
esc al ati o n a n d m ai nte n a nce p h ase  
T ar g et 
d ose  
U nit  
Visit 2  
R a n d o mis ati o n  
Visit 4  
Wee k 2  
Visit 6  
Wee k 4  
Visit 9  
Wee k 8  
Visit 1 2  
Wee k 1 2  
& u ntil E n d of 
tre at me nt 
2. 4 m g   D ose i n m g  
0. 2 5  
0 .5  
1. 0  
1. 7  
2. 4  
V ol u me i n m L  
0. 0 8  
0. 1 7  
0. 3 4  
0. 5 7  
0. 8 0  
V al ue s h o w n i n d ose c o u nter 
8  
1 7  
3 4  
5 7  
8 0  
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
4 8
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
4 9  of 1 1 6  
 
T a ble  6 -4  
P art 2 a a n d 2 b. D osi n g det ails f or se m a gl uti de B 3. 0 m g/ m L P D S 2 9 0 d uri n g t he 
esc al ati o n a n d m ai nte n a nce p h ase  
T ar g et 
d ose  
U nit  
Visit 2  
Wee k 0  
Visit 3  
Wee k 2  
Visit 4  
Wee k 4  
Visit 5  
Wee k 6  
Visit 6  
Wee k 8  
Visit 7  
Wee k 1 2  
M ai nte n a nce  
Visit 1 0  
Wee k 3 2  
R a n d o mis ati o n 
& u ntil E n d of 
tre at me nt 
2. 4 m g   D ose i n m g  
0. 2 5  
0. 5  
1. 0  
1. 7  
2. 4  
2. 4  
2. 4  
V ol u me i n m L  
0. 0 8  
0. 1 7  
0. 3 4  
0. 5 7  
0. 8 0  
0. 8 0  
0. 8 0  
V al ue s h o w n i n 
d ose c o u nter  
8  
1 7  
3 4  
5 7  
8 0  
8 0  
8 0  
 
T a ble  6 -5  
P art 2 b. D osi n g det ails f or N N C 0 1 6 5 -1 8 7 5 a n d c orres p o n di n g pl ace b o ar ms 
d uri n g t he esc al ati o n a n d m ai nte n a nce p h ases usi n g t he N o v o Pe n ® 4  
T ar g et 
d ose  
U nit  
Visit 1 0  
R a n d o mis ati o n  
Wee k 3 2  
Visit 1 1  
Wee k 3 4  
Visit 1 2  
Wee k 3 6  
Visit 1 3  
Wee k 3 8   
Visit 1 3 b  
Wee k 4 0  
Visit 1 4  
Wee k 4 2  & u ntil  
E n d of 
tre at me nt 
1. 0 m g   D ose i n m g  
0. 0 5  
0. 1  
0. 2 5  
0. 5  
1. 0  
1. 0  
m g/ ml  
5. 0  
5. 0  
5. 0  
5. 0  
5. 0  
5. 0  
V ol u me i n m L  
0. 0 1  
0. 0 2  
0. 0 5  
0. 1  
0. 2  
0. 2  
V al ue s h o w n i n 
d ose c o u nter  
1  
2  
5  
1 0  
2 0  
2 0  
2. 0 m g  D ose i n m g  
0. 0 5  
0. 1  
0. 2 5  
0. 5  
1. 0  
2. 0  
m g/ ml  
5. 0  
5. 0  
5. 0  
5. 0  
5. 0  
5. 0  
V ol u me i n m L  
0. 0 1  
0. 0 2  
0. 0 5  
0. 1  
0. 2  
0. 4  
V al ue s h o w n i n 
d ose c o u nter  
1  
2  
5  
1 0  
2 0  
4 0  
 
All s u bjects s h o ul d ai m t o reac h t h e rec o m me n de d tar get d ose of N N C 0 1 6 5-1 8 7 5/ place b o a n d 
se ma gl uti de wit hi n t heir ar m. 
•  I n case of u nacce pta bl e A Es as j u d ge d b y t he i n v esti gat or, d os e escalati o n ma y b e p ost p o ne d b y 
1 -2  wee k s at t he discreti o n of t he i n vesti gat or. T his s h o ul d o nl y b e all o w e d if t he s u bject w o ul d 
ot her wise disc o nti n ue tri al pr o d uct c o m pletel y a n d if c o nsi dere d s afe t o c o nti n ue t he trial 
pr o d uct, as per t he i n vesti gat or’s discreti o n.  
•  If a s u bject d o es n ot t olerate t he ra n d o mise d t ar get d ose, t he s u bject ma y sta y at a l o wer d os e 
le vel. T his s h o ul d o nl y b e all o we d if t he s u bject w o ul d ot her wise disc o nti n ue trial pr o d uct 
c o m pletel y a n d if c o nsi d ere d safe t o c o nti n ue o n trial pr o d uct, as per i n vesti gat or’s discreti o n.  
•  t he l o wer d ose le v el is at t he discreti o n of t he i n vesti gat or  
•  F or part 1; b ot h N N C 0 1 6 5 -1 8 7 5/ place b o a n d s e ma gl uti de s h o ul d be re d uce d if t he s u bject d oes 
n ot t olerate t he ra n d o mise d tar get d ose  
•  F or part 2 b; N N C 0 1 6 5 -1 8 7 5/ place b o s h o ul d be re d uce d if t he s u bject d oes n ot t olerate t he 
ra n d o mise d tar get d os e. Se ma gl utide s h o ul d prefera bl y st a y at 2. 4 m g b ut is all o we d t o be 
re d uce d, as per i n v esti gat or’s discreti o n 
•  I n case of de viati o ns fr o m t he pla n ne d d ose es cal ati o n re gi me n, it is rec o m me n de d t hat t he 
s u bject ma ke at least o ne atte m pt t o re-escalate t o t he rec o m me n d e d tar get le vel d ose, as p er t he 
i n vesti gat or’s discreti o n. 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
4 9
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5 0  of 1 1 6  
 
•  It is rec o m me n de d t hat t h e i n vesti gat or c o ns ults N o v o N or dis k i n case of persiste nt de viati o ns 
fr o m t he pla n ne d escalati o n re gi me n. 
A d ose re mi n der car d will be ha n de d o ut t o t he s u bjects at eac h s ite visit d uri n g t he escal ati o n 
peri o d. T he ha n d o ut d ose re mi n der car d will c o ntai n i nf or mati o n o n:  
•  T he d ose t o be ta k e n u ntil ne xt site visit  
•  A re mi n der f or t he s u bject t o bri n g trial pr o d u ct t o site f or t he d osi n g at site.  
N o n -i n vesti g ati o n al me dici n al pr o d ucts  
N ot a p plica ble.  
A u xiliar y s u p plies will b e pr o vi de d b y N o v o N or dis k i n acc or da n ce wit h t he trial materials ma n u al 
( T M M) ( See T a ble  6 -6 ). 
T a ble  6 -6  
A u xili ar y s u p plies pr o vi de d b y N o v o N or dis k  
A u xili ar y s u p pl y  
Det ails  
Nee dles  
N o v o Fi ne Pl us 3 2 G, 4 m m  
N o v o Fi ne 3 2 G, 6 m m  
De vice  
N o v o P e n ®  4  
Directi o ns f or use ( D F U)  
D F U f or N o v o P e n ®  4  
D F U f or P D S 2 9 0 pe n -i nj ect or 
O nl y nee dles pr o vi de d a n d a p pr o ve d b y N o v o N or dis k m ust be use d f or a d mi nistrati o n of trial 
pr o d uct.  
6. 1. 1  
Me dic al de vices  
6. 1. 1. 1  
I n vesti g ati o n al me dic al de vices 
N ot a p plica ble f or t his trial.  
6. 1. 1. 2  
N o n -i n vesti g ati o n al me dic al de vices 
N o n -i n vesti gati o nal me dical de vices are liste d i n Secti o n 6. 1  as a u xiliar y s u p plies.  
N o v o Pe n ®  4 is a d ura ble de vice w hic h is n ot u n der i n vesti gati o n i n t his trial. N o v o Pe n®  4 is a 
re usa ble dial-a-d ose p e n -i nject or desi g ne d t o be us e d wit h N o v o N or dis k Pe nfill®  3 m L cartri d ges. 
It c a n deli ver d oses fr o m 1 t o 6 0 u nits i n i ncre me nts of 1 u nit. O ne u nit (i ncre me nt) is e q ui vale nt t o 
1 0 µ L, t h u s t he pe n-i nject or ca n deli ver v ol u mes fr o m 1 0 µ L t o 6 0 0 µ L. T h e user ca n dial u p a n d 
d o w n i n or der t o a dj ust a d ose. N o v o Pe n ®  4 was C E -mar ke d i n 2 0 0 5 i n acc or da nce wit h A n ne x II i n 
t he Me dical De vi ce Directi ve 9 3/ 4 2 E E C. T he i n vesti gat or m ust d oc u me nt t hat t he D F U is gi ve n t o 
t he s u bject orall y a n d i n writi n g at t he first dis pe nsi n g visit.  
I nf or mati o n a b o ut t he N o v o Pe n®  4 a n d P D S 2 9 0 pr e -fille d pe n-i nject or ma y be f o u n d i n t he 
N N C 0 1 6 5 -1 8 7 5 I n vesti gat or’s Br oc h ure a n d a n y u p dates here of 3 6. I nf or m ati o n a b o ut t he use of t he 
N o v o Pe n ®  4 a n d t he P D S 2 9 0 pre -fille d pe n-i nject or f or se ma gl uti de a n d se ma gl uti de place b o ca n 
be f o u n d i n t he D F U.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
5 0
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5 1  of 1 1 6  
 
Tr ai ni n g i n t he me dic al de vices  
T he s u bjects m ust be trai ne d acc or di n g t o t he D F U i n h o w t o ha n dle t he N o v o Pe n ® 4 a n d t he 
P D S 2 9 0 pe n -i nject or, w h e n han de d o ut t he first ti me.  
T he i n vesti gat or m ust d oc u me nt t hat trai ni n g i n D F U has b ee n gi ve n t o t he s u bjects orall y a n d i n 
writi n g at t he first dis pe nsi n g visit. Trai ni n g m ust be re peate d d uri n g t he tri al at re g ular i nter vals i n 
or der t o e ns ur e c orrect use  of t he me dical de vice. Trai ni n g is t he res p o nsi bilit y of t he i n vesti gat or or 
a dele gat e.  
6. 2  
Pre p ar ati o n/ h a n dli n g/st or a ge/ acc o u nt a bilit y  
O nl y s u bjects ra n d o mise d t o treat me nt ma y use trial pr o d uct a n d o nl y dele gat e d site staff ma y 
s u p pl y or a d mi nister trial pr o d uct.  
•  Eac h site will be s u p plie d wit h s ufficie nt trial pr o d ucts f or t he trial o n a n o n g oi n g basis. Trial 
pr o d uct will be distri b ute d t o t he sites acc or di n g t o scree ni n g a n d ra n d o misati o n.  
•  T he i n vesti gat or or desi g nee m ust c o nfir m t hat a p pr o priate te m per at ure c o n diti o ns ha ve bee n 
mai ntai ne d d uri n g tra nsit f or all trial pr o d ucts r ecei ve d, a n d t hat a n y discre pa ncies are re p orte d 
a n d res ol ve d b ef ore use of t he trial pr o d ucts.  
•  All trial pr o d ucts m ust be st ore d i n a sec ure, c o ntr olle d, a n d m o nit ore d ( ma n ual or  a ut o mate d) 
area i n acc or da n ce wit h t he la belle d st ora ge c o n diti o ns wit h access li mite d t o t he i n vesti gat or 
a n d dele gat e d site staff.  
•  T he i n vesti gat or m ust i nf or m N o v o N or dis k i m me diatel y if a n y trial pr o d uct has bee n st ore d 
o utsi de s pecifie d c o n diti o ns. T he trial pr o d uct m ust n ot be dis pe nse d t o a n y s u bject b ef ore it has 
bee n e v al uate d a n d a p pr o ve d f or f urt her use b y N o v o N or dis k. A d diti o nal details re gar di n g 
ha n dli n g of te m p erat ur e de viati o ns ca n be f o u n d i n t he trial materials ma n u al ( T M M).  
•  T he i n vesti ga t or or desi g nee is res p o nsi ble f or dr u g acc o u nta bilit y a n d rec or d mai nte na nce (i.e., 
recei pt, acc o u nta bilit y a n d fi nal dis p ositi o n rec or ds). 
•  
T he i n vesti gat or or desi g nee m ust i nstr uct t he s u bject i n w hat t o ret ur n at ne xt visit.  
•  
Dr u g acc o u nta bilit y s h o ul d be perf or m e d o n a pe n le vel a n d m ust be d oc u me nte d i n t he I W R S  
f or Part 2 a n d t he e C R F  for Part 1   
•  
T he s u bject m ust ret ur n all use d, partl y use d a n d u n use d trial pr o d uct i ncl u di n g e m pt y 
pac ka gi n g materials d uri n g t he trial as i nstr ucte d b y t he i n vesti gat o r. 
•  Destr ucti o n of trial pr o d ucts ca n be p erf or me d o n a n o n g oi n g b asis a n d will be d o ne acc or di n g 
t o l ocal pr oce d ures after acc o u nta bilit y is fi nalise d b y t he site a n d rec o ncil e d b y t h e m o nit or.  
•  All ret ur ne d, u n-us e d,  e x pire d or da ma ge d trial pr o d ucts (f or tec h nical c o m plai nt sa m ples, see 
Secti o n 1 0. 5 ) m ust be st ore d se paratel y fr o m n o n-all ocate d trial pr o d u cts. N o te m perat ur e 
m o nit ori n g is re q uire d.  
•  N o n -all ocate d trial pr o d u cts i ncl u di n g e x pire d or da ma ge d pr o d u cts m ust be acc o u nte d as 
u n use d, at t he latest at cl os ure of t he site.  
6. 3  
Me as ures t o mi ni mise bi as: R a n d o mis ati o n a n d bli n di n g  
R a n d o mis ati o n  
F or Part 2 a ll s u bjects will be ce ntrall y scree n e d a n d ra n d o mise d usi n g a n I W R S a n d assi g ne d t o t he 
ne xt a vaila ble treat me nt acc or di n g t o r a n d o misati o n sc he d ule. Trial pr o d uct will be 
dis pe nse d/all ocate d at t he trial visits s u m marise d i n t he fl o wc hart.  As s u bj ects o n treat me nt wit h 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
5 1
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5 2  of 1 1 6  
 
N N C 0 1 6 5 -1 8 7 5 /place b o 2. 0 m g  nee d t o be cl osel y m o nit ore d f or safet y a n d t olera bilit y, t he 
ra n d o misati o n of t he 2. 0 m g d ose gr o u ps  will be restricte d t o 1 -3 sites.   
F or Part 1  the s p ecific tr eat me nt f or a s u bject will be assi g n e d usi n g a ra n d o misati o n list. P ote ntial 
bias will be re d uce d b y ce ntral ra n d o misati o n. All s u bjects will be assi g n e d a u ni q ue n u m ber 
(ra n d o misati o n n u m ber) i n asce n di n g n u meri cal or der. T he ra n d o misati o n n u m ber e nc o d es t he 
s u bject’s assi g n me nt t o x of y tr eat me nt ar ms i n t he trial acc or di n g t o t he ra n d o misati o n  sc he d ule 
ge n erat e d bef ore t he trial. F or f urt her i nstr ucti o n, see t he T M M.  
O pe n -l a bel 
•  Se ma gl uti de B 3. 0 m g/ m L  
Bli n di n g  
T he acti ve dr u g a n d pla ce b o are vis u all y i de ntical f or t he f oll o wi n g trial pr o d ucts:  
•  N N C 0 1 6 5 -1 8 7 5 1. 0 m g/ N N C 0 1 6 5 -1 8 7 5 1. 0 m g place b o  
•  N N C 0 1 6 5 -1 8 7 5 2. 0 m g/ N N C 0 1 6 5 -1 8 7 5 2. 0 m g place b o  
F or Part 2 t he I W R S is use d f or bli n d -brea ki n g. I n case of a n e mer ge nc y, t h e i n vesti gat or has t he 
s ole res p o nsi bilit y f or d eter mi ni n g if u n bli n di n g of a s u bject’s treat me nt is warra nte d. S u bject safet y 
m ust al wa ys b e t he first c o nsi derati o n i n ma ki n g s uc h a deter mi nati o n. If t h e i n vesti gat or deci d es 
t hat u n bli n di n g is warra nte d, t he i n vesti gat or s h o ul d ma ke e ver y eff ort t o c o ntact N o v o N or dis k 
pri or t o u n bli n di n g a s u bj ect ’s treat me nt u nless t his c o ul d dela y e mer ge nc y treat me nt of t he s u bject. 
If a s u bject’s treat me nt is u n bli n de d, N o v o N or dis k ( Gl o bal Safet y de p art m e nt) m ust be n otifie d 
wit hi n 2 4 h o urs after brea ki n g t he bli n d. T he d ate a n d reas o n t h at t he bli n d was br o ke n m ust be 
rec or de d i n t he s o urce d o c u me ntati o n. T he pers o n brea ki n g t he bli n d m ust pri nt t he “c o de brea k 
c o nfir mati o n ” n otificati o n ge n erat e d b y t he I W R S, si g n a n d d ate t he d oc u m e nt. If I W R S is n ot 
accessi ble at t he ti me of bli n d brea k, t he I W R S hel p  des k s h o ul d be c o ntact e d. C o ntact details a re 
liste d i n Attac h me nt I . 
F or Part 1 T hree s ets of seale d c o d es c o ntai ni n g tr eat me nt i nf or mati o n f or eac h s u bject will be  
pre pare d. T he s eale d c o d es will be retai ne d b y t h e  i n vesti gat or (C R O ), t h e l ocal N o v o N or dis k 
affiliate a n d t he N o v o N or dis k Gl o bal S afet y de part me nt i n a sec ure d area. I n case of a n  e m er ge n c y, 
t he i n vesti gat or h as t he s ole res p o nsi bilit y f or d eter mi ni n g if u n bli n di n g of a s u bjects’ treat me nt is 
warra nte d. S u bject safet y m ust al wa ys b e t he first c o nsi derati o n i n  ma ki n g s uc h a deter mi nat i o n. If 
t he i n vesti gat or d eci des t hat u n bli n di n g is warra nt e d, t he i n vesti gat or s h o ul d ma ke e ver y eff ort t o 
c o ntact N o v o N or dis k ( Gl o bal Safet y  d e part me nt) pri or t o u n bli n di n g a s u bj ect’s treat me nt, u nless 
t his c o ul d dela y e mer ge n c y tr eat me nt of t h e s u bjec t. If a s u bject’s treat me nt is u n bli n de d, N o v o 
N or dis k  ( Gl o bal Safet y d e part me nt) m ust be n otifi e d wit hi n 2 4 h o urs after brea ki n g t he bli n d. 
T he date w h e n a n d reas o n w h y t he bli n d w as br o ke n m ust be rec or de d i n t h e s o urce  d o c u me ntati o n.  
O nce t he trial is c o m plet e, all har d c o p y c o des (s eale d a n d o pe n e d) m ust be acc o u nte d  f or at t he 
site. T he c o des will be c ollecte d b y t he m o nit or at trial cl os ure visit. Treat m e nt all ocati o n will als o 
be accessi ble t o s pecial l a bora t ory  res p o nsi ble f or P K a nal ysis.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
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1
 |
 of
  Pr ot oc ol  versi o n 4. 0
5 2
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5 3  of 1 1 6  
 
6. 4  
Tre at me nt c o m pli a nce  
Dr u g tre at me nt c o m pli a nce  
T hr o u g h o ut t he tri al, t he i n vesti gat or will re mi n d t he s u bjects t o f oll o w t he trial pr oce d ures a n d 
re q uire me nts t o e n c o ura ge s u bject c o m plia nce. 
D osi n g will be a d mi nistere d o n site at all site visits, f or b ot h  Part 1 a n d Part 2. I n bet wee n t he visits 
t he s u bjects will self-a d mi nister trial pr o d uct at h o me.  
W he n d osi n g at site  
W he n at t he site t he s u bjects will be d ose d b y t he i n vesti gat or or d esi g nee, u n der me dical 
s u per visi o n. T he date a n d ti me of eac h d os e a d mi nistere d at t he site will be rec or de d i n t he s o urce 
d oc u me nts.  
W he n d osi n g at h o me  
W he n s u bjects self -a d mi nister trial pr o d uct(s) at h o me, c o m plia nce wit h tri al pr o d uct a d mi nistrati o n 
will be assesse d a n d t he assess me nt d oc u me nte d i n s o urce d oc u m e nts a t eac h visit w here 
i nf or mati o n is a vaila ble. If a n y s us pici o n of n o n-c o m plia nce arises, a part fr o m occasi o nall y t he site 
m ust e nter i nt o a dial o g u e wit h t he s u bject, re -e m p hasi si n g t he i m p orta nce of c o m plia nce a n d 
u nc o ver barriers t o c o m plia nce. T his dial o g ue m ust be d oc u me nte d. C o m plia nce will be ass esse d b y 
cr oss c hec ki n g t he f oll o wi n g s o ur ces a n d c o m pari n g t hese t o t he e x pecte d use.  
•  Dr u g acc o u nta bilit y i nf or mati o n : c o u nti n g ret ur n e d trial pr o d uct, vis ual i ns pecti o n of pe ns  
•  Re vie w of d osi n g diaries  
•  Q uesti o ni n g of s u bjects  
Treat me nt date, ti me, tri al pr o d uct ta ke n, i njecte d d ose, d ose u nit, i njecti o n site a n d l ocati o n of 
i njecti o n are rec or de d i n t he C R F. 
6. 5  
C o nc o mit a nt me dic ati o n  
A n y me di cati o n (i ncl u di n g o ver t he c o u nter or prescri pti o n me dici nes ) ot h er t ha n t he trial pr o d u cts 
t hat t he s u bject is recei vi n g at t he ti me of t h e first visit or recei ves d uri n g t h e trial m ust be rec or de d 
al o n g wit h:  
•  Tra de n a me or ge n eric n a me  
•  I n dic ati o n 
•  D ose, U nit a n d Fre q ue n c y  
•  Dates of a d mi nistrati o n i ncl u di n g start a n d  st o p dates 
D uri n g t h e trial s u bjects s h o ul d n ot i nitiate a n y wei g ht ma n a ge me nt treat me nt (e. g. , me dicati o n)  
w hic h is n ot part of t he trial pr oce d ures. If s uc h treat me nt is i nitiate d, t he s u bject s h o ul d be  
i nstr ucte d t o st o p t he wei g ht ma na ge me nt treat me nt. 
C ha n ges i n c o nc o mita nt me dicati o n m ust be rec or de d at eac h visit. If a c h a n ge is d u e t o a n A E, t he n 
t his m ust be re p orte d acc or di n g t o A p p e n di x 3, Secti o n 1 0. 3 . 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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5 3
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5 4  of 1 1 6  
 
6. 6  
D ose m o dific ati o n  
N ot a p plica ble f or t his trial. Please refer t o Secti o n 6. 1  f or descri pti o n of misse d d ose(s) a n d f or 
g ui da n ce o n d ose re d ucti o n i n case  t he s u bject d oes n ot t olerate t he ra n d o mise d tar get d ose. 
6. 7  
Tre at me nt after e n d of tri al  
W he n disc o nti n ui n g trial pr o d ucts, eit her at t he s c he d ule d ‘e n d of treat me nt’ visit or if trial pr o d uct 
is disc o nti n ue d, t he s u bject s h o ul d be treate d at t he discreti o n of t he i n vesti gat or. 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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5 4
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5 5  of 1 1 6  
 
7  Disc o nti n u ati o n of tri al tre at me nt a n d s u bject  
disc o nti n u ati o n/ wit h dr a w al  
Treat me nt of a s u bject m a y b e disc o nti n ue d at a n y ti me d uri n g t he trial at t h e discreti o n of t he 
i n vesti gat or f or safet y, be ha vi o ural, c o m plia nce or a d mi nistrati ve reas o ns. 
Eff orts m ust be ma de t o ha ve s u bjects atte n d a n d c o m plete all sc he d ule d visit pr oce d ures. S u bjects 
m ust be i nf or me d a b o ut t he c o nti n ue d scie ntific i m p orta nce of t h eir data , e ve n if t he y disc o nti n ue 
trial pr o d uct. O nl y s u bjects w h o wit h dra w c o nse nt will be c o nsi dere d as wit h dra w n fr o m t he trial. 
7. 1  
Disc o nti n u ati o n of tri al tre at me nt  
Disc o nti n uati o n of trial treat me nt ca n b e deci d e d b y b ot h t he i n vesti gat or a n d t he s u bject. T he trial 
treat me nt ma y be disc o nti n ue d at t he discreti o n of t he i n vesti gat or f or safet y, be h a vi o ural, 
c o m plia nce or a d mi nistrati ve reas o ns.  
T he s u bject m ust be disc o nti n ue d fr o m trial pr o d u ct, if a n y of t he f oll o wi n g a p plies f or t he s u bject:  
1.  Safet y c o ncer n as  j u d ge d b y t he i n vesti gat or 
2.  Pre g n a nc y  
3.  I nte nti o n of b ec o mi n g pre g n a nt 
4.  Si m ulta ne o us use of a n a p pr o ve d or n o n -a p pr o ve d i n vesti gati o nal me dici nal pr o d uct i n a n ot her 
cli nical trial  
5.  S us pici o n of pa ncreatitis  
6.  A n u nacce pta ble A E d efi ne d as a n y se v ere A E a n d/ or seri o us A E ( S A E) j u d ge d as pr o ba bl y or 
p ossi bl y relate d t o tri al pr o d uct b y t h e i n vesti gat or  
If ac ut e pa ncreatitis is s us pecte d a p pr o priate ma na ge m e nt s h o ul d be i nitiate d, i ncl u di n g l ocal 
meas ure me nt of a m yl ase a n d li pase ( A p p e n di x 3, Secti o n 1 0. 3. 3 ) 
S u bjects meeti n g disc o nti n uati o n of treat me nt crit eri a n o. 1, 2 a n d 3 are all o we d t o res u me trial 
pr o d uct if t he criteria are n o l o n ger met.  
S u bjects meeti n g disc o nti n uati o n criteri o n n o. 5 a re all o we d t o res u m e trial pr o d uct if t he Atla nta 
criteria 4 0 are n ot f ulfille d a n d t h us t he s us pici o n of ac ute pa n creatitis is n ot c o nfir me d.  
T he pri mar y reas o n f or disc o nti n uati o n of trial pr o d uct m ust be s pecifie d i n t he e n d -of -treat me nt-
f or m i n t he e C R F, a n d fi nal dr u g acc o u nta bilit y m ust be perf or me d. F or Part 2 a  treat me nt 
disc o nti n uati o n sessi o n m ust be ma de i n t he I W R S.  
Eff orts m ust be ma de t o ha ve s u bjects i n Part 1 a n d Part 2 b, w h o disc o nti n ue trial pr o d uct, atte n d 
a n d c o m plete all sc h e d ule d visit pr oce d ures. O nl y s u bjects w h o wit h dra w c o nse nt will be 
c o nsi dere d wit h dr a w n fr o m t he trial. S u bjects m ust be e d ucate d a b o ut t he c o nti n ue d scie ntific 
i m p orta nce of t heir d ata, e ve n if t he y disc o nti n ue trial pr o d uct. 
S u bjects w h o disc o nti n ue trial pr o d uct i n Part 1 or Part 2 b s h o ul d be e nc o ura ge d t o c o nti n ue wit h 
t he sc he d ule d visits a n d assess me nts u ntil t he ti me of t he ori gi nall y s c he d ule d e n d of treat me nt visit 
( V 1 5 f or Part 1 a n d V 1 8 f or Part 2 b) a n d e n d of tri al visit ( V 1 7 f or Part 1 a n d V 1 9 f or Part 2 b) t o 
e ns ure c o nti n ue d d ata c ollecti o n.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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1
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1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5 6  of 1 1 6  
 
If t he s u bject d oes n ot wis h t o atte n d t he sc he d ule d cli nic visits eff orts s h o ul d be ma de t o ha ve t h e 
visits c o n verte d t o p h o ne c o ntacts. H o w e ver, all eff orts s h o ul d be ma de t o h a ve t he s u bject atte n d at 
least t he ‘e n d of treat me nt’ visit ( V 1 5 f or Part 1 a n d V 1 8 f or Part 2 b) a nd t he ‘e n d of tri al’ visit 
( V 1 7 f or Part 1 a n d V 1 9 f or Part 2 b). 
T he visit g ui da nce pr o vi de d i n t he pr ot oc ol fl o wc hart m ust be f oll o we d t o t he e xte nt p ossi ble. 
H o we ver, f or s u bjects w h o ha ve disc o nti n ue d treat me nt > 8 wee ks pri or t o t he e n d -of -treat me nt 
vi sit ( V 1 5 f or Part 1 a n d V 1 8 f or Part 2 b) a n d u n d er n o cir c u msta nces are willi n g t o s h o w u p f or t h e 
sc he d ule d e n d-of -trial visit ( V 1 7 f or Part 1 a n d V 1 9 f or Part 2 b) acc or di n g t o t he pr ot oc ol, t he site 
ca n s u g gest t o c o m bi ne t he t w o visits.  
S u bjects w h o dis c o nti n ue trial pr o d uct i n Part 2a a n d w here re -i nitiati o n a n d re-es calati o n t o t he 
tar get d ose le v el of o nce-wee kl y se ma gl uti de 2. 4 m g bef ore wee k 2 8  is n ot p ossi ble at t he 
i n vesti gat or’s discreti o n s h o ul d atte n d t he e n d-of -trial visit a p pr o xi matel y 8 wee ks after act ual last 
d osi n g of se m a gl uti de.  
If t he s u bject ( Part 1 a n d Part 2) ref us es t o atte n d t he ‘e n d of tr eat me nt’ a n d/ or ‘e n d of trial’ visit, 
i nf or mati o n a b o ut t he atte m pts t o f oll o w u p wit h t he s u bject m ust be d oc u me nte d i n t he s u bject’s 
me dical rec or d.  
7. 1. 1  
Te m p or a r y disc o nti n u ati o n of tri al tre at me nt  
If a s u bject h as disc o nti n ue d trial pr o d uct, t he s u bject s h o ul d f oll o w t he g ui de f or misse d d oses (s ee 
Secti o n 6. 1 ) if treat me nt s h o ul d be res u me d. 
If a “tr eat me nt stat us” s essi o n pre vi o usl y has b ee n ma de i n I W R S t o i n dicate disc o nti n uati o n of trial 
pr o d uct, a ne w “treat me nt stat us” sessi o n m ust be ma de t o res u me trial pr o d uct. 
7. 2  
S u bject disc o nti n u ati o n/ wit h dr a w al fr o m t he tri al  
A s u bject ma y wit h dra w c o nse nt at a n y ti me at his/ her o w n re q u est.  
If a s u bject wit h dra ws c o nse nt, t he i n vesti gat or m ust as k t he s u bject if he/s he is willi n g, as s o o n as 
p ossi ble, t o ha ve assess m e nt perf or m e d acc or di n g t o t he  e n d-of -tr eat me nt-visit ( V 1 5 f or Part 1 a n d 
V 1 8 f or Part 2). See t he fl o wc hart f or data t o be c ollecte d.  
Fi nal dr u g acc o u nta bilit y m ust be perf or me d e ve n if t he s u bject is n ot a ble t o c o me t o t he site. A 
treat me nt disc o nti n uati o n sessi o n m ust be ma de i n t he I W R S.  
If t he s u bject wit h dra ws c o nse nt, N o v o N or dis k ma y retai n a n d c o nti n ue t o use a n y data c ollecte d 
bef ore s u c h a wit h dr a wal of c o nse nt.  
If a s u bject wit h dra ws fr o m t he trial, he/s he ma y re q uest destr ucti o n of a n y sa m ples ta ke n a n d n ot 
teste d, a n d t he i n vesti gat or m ust d oc u me nt t his i n t he me dical rec or d. 
Alt h o u g h a s u bject is n ot o bli ge d t o gi ve his/ her reas o n(s) f or wit h dra wi n g, t he i n vesti gat or m ust 
ma ke a reas o na bl e eff ort t o ascertai n t he reas o n(s), w hile f ull y res pecti n g t h e s u bject ’s ri g hts. 
W here t he reas o ns are o btai ne d, t he pri mar y reas o n f or wit h dra wal m ust be s pecifie d i n t he e n d of 
trial f or m i n t he C R F. 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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V V- T M F- 5 0 4 2 3 4 5
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1
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5 6
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5 7  of 1 1 6  
 
7. 2. 1  
Re pl ace me nt of s u bjects  
S u bjects w h o disc o nti n ue trial pr o d uct or wit h dra w fr o m trial will n ot be re place d.  
7. 3  
L ost t o f ol l o w-u p  
A s u bject will be c o nsi dere d l ost t o f oll o w -u p if he or s he re peat e dl y fails t o ret ur n f or sc he d ule d 
visits a n d is u na ble t o be c o ntacte d b y t he site.  
T he f oll o wi n g acti o ns m ust be ta ke n if a s u bject f ails t o ret ur n t o t he site f or a re q uir e d visit:  
•  T he site m ust atte m pt t o c o ntact t he s u bject a n d resc he d ule t he misse d visit as s o o n as p ossi ble 
a n d c o u nsel t he s u bject o n t he i m p orta nce of m ai ntai ni n g t he assi g ne d visit sc he d ule a n d 
ascert ai n w het her or n ot t he s u bject wis hes t o a n d/ or s h o ul d c o nti n ue  i n t he trial. 
•  Bef ore a s u bj ect is dee m e d l ost t o f oll o w -u p, t he i n vesti gat or or desi g nee m ust ma ke e ver y 
eff ort t o r e gai n c o ntact wit h t he s u bject ( w here p ossi ble, at least t hree tele p h o ne calls a n d, if 
necessar y, a certifie d lett er t o t he s u bject ’s last k n o w n maili n g a d dress or l ocal e q ui vale nt 
met h o ds). T hese c o nt act atte m pts s h o ul d be d oc u me nte d i n t he s u bject ’s s o urce d oc u m e nt. 
•  S h o ul d t he s u bject c o nti n ue t o be u nreac ha bl e at t he e n d-of -trial visit ( V 1 5 f or Part 1 a n d V 1 8  
f or Part 2), he/s h e will be c onsi dere d t o ha ve wit h dra w n fr o m t he trial wit h a pri mar y reas o n of 
‘l ost t o f oll o w-u p ’. 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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1
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 of
  Pr ot oc ol  versi o n 4. 0
5 7
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5 8  of 1 1 6  
 
8  Tri al assess me nts a n d pr oce d ures  
T he f oll o wi n g s ecti o ns d escri be t he assess me nts a n d pr oce d ures, w hile t heir ti mi n g is s u m marise d 
i n t he fl o wc hart. 
•  I nf or me d c o ns e nt m ust be o btai ne d bef ore a n y trial relate d acti vit y, see Secti o n 1 0. 1. 3 . 
•  All scree ni n g e v al uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial s u bjects 
meet all i ncl usi o n criteria a n d n o ne of t he e x cl usi o n criteria.  
•  T he i n vesti gat or will mai ntai n a scr ee ni n g l o g t o r ec or d det ails of all s u bjects scree ne d a n d t o 
c o nfir m eli gi bilit y or rec or d reas o n f or scree n fail ure, as a p plica ble.  
•  At scree ni n g, s u bjects will be pr o vi de d wit h a car d stati n g t hat t he y are partici pati n g i n a trial 
a n d gi vi n g c o nt act detai ls of rele va nt site staff t hat ca n be c o nt acte d i n case of e mer ge nc y.  
•  A d here n ce t o t he trial d esi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he fl o wc hart, is 
esse ntial a n d re q uire d f or trial c o n d uct.   
•  T he i n vesti gat or m ust e ns ure t o kee p re g ular c o nt ac t wit h eac h s u bject t hr o u g h o ut t he e ntire 
trial, a n d al wa ys h a ve u p date d c o ntact i nf or mati o n. E ve n if a visit is misse d a n d it is n ot 
p ossi ble t o resc he d ule, e ver y eff ort m ust be ma de t o ha ve all s u bjects f oll o we d f or t he pri mar y 
e n d p oi nt a n d A Es.  
•  It is t he res p o nsi bilit y of t he i n vesti gat or t o sc he d ule t he visits a n d c o ntacts as per t he pr ot o c ol 
fl o wc hart (s ee Secti o n 1. 2 ) a n d t o e ns ure t he y ta ke place. See Secti o n 6. 4  f or treat me nt 
c o m plia nce. 
•  Assess me nts s h o ul d be c o n d ucte d acc or di n g t o t he cli nic’s sta n dar d of prac tice u nless ot her wis e 
s pecifie d i n t he c urre nt s ecti o n. Eff orts s h o ul d be ma de t o li mit t he bias bet wee n ass ess me nts. 
T he s u g geste d or d er of t h e assess me nts:  
1.  E C G  a n d vital si g ns  
2.  Bl o o d a n d uri ne s a m ples  
3.  Me ntal healt h assess me nts i nstr u me nts (see Secti o n 8. 2. 1 ) 
4.  Ot her assess me nts  
•  Diaries will i ncl u de t he f oll o wi n g i n relati o n t o t he visit t he y s u p p ort:  
•  Re mi n ders:  
▪ t o atte n d visit fasti n g (see fl o wc hart i n Secti o n 1. 2 ) 
▪ t o ret ur n trial pr o d uct at ne xt site visit 
▪ t o ret ur n diar y at n e xt site visit 
▪ t o perf or m 2 4-h o ur uri ne c ollecti o n  
•  I nstr u cti o n o n h o w t o use t he diar y  
•  I nf or mati o n t o be c ollecte d: 
▪ date of all d osi n g at h o m e (see Secti o n 6. 1 ) 
▪ wee kl y e v al uati o n of w h et her d osi n g i nstr ucti o ns ha ve bee n f o ll o we d  
▪ date a n d ti me of last d ose pri or t o P K visit  
▪ 2 4 -h o ur uri ne c ollecti o n  
▪ healt h iss ues  
•  S u bjects m ust recei ve trai ni n g i n h o w t o c ollect d osi n g i nf or mati o n i n t he desi g nat e d pa per 
diar y.  
•  O nl y t he s u bject ca n ma k e e ntries a n d c orrecti o ns i n t he diaries,  u nless t he secti o n is s pecifie d 
f or site staff. 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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V V- T M F- 5 0 4 2 3 4 5
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5 8
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
5 9  of 1 1 6  
 
•  S o urce data of cli nical assess me nts perf or m e d a n d rec or de d i n t he e C R F m ust be a vaila ble a n d 
will us uall y b e t he s u bject’s me dical rec or ds. A d diti o nal rec or di n gs t o be c o nsi dere d s o urce data 
i ncl u de, b ut are n ot li mite d t o, la b orat or y re p orts, E C G, diar y rec or di n gs, cli nical o utc o me 
assess me nts. E ns ure t o tra nscri be i nt o t he e C R F:  
•  E val uati o n of E C G  
•  I nf or mati o n c ollect e d i n t he diar y 
•  S u bject’s wei g ht hist or y m ust be rec or de d i n t he s u bject’s me dical r ec or d.  
•  Re vie w of diaries, E C G, la b orat or y re p orts etc. m ust be d oc u me nte d eit her o n t he d oc u me nts or 
i n t he s u bject's s o ur ce d o c u me nts. If clarificati o n of e ntries or discre pa n cies i n t he diar y is 
nee de d, t he s u bject m ust be q uesti o ne d, a n d a c o n cl usi o n ma de i n t he  s u bject’s s o urce 
d oc u me nts. Care m ust be ta ke n n ot t o bias t he s u bject.  
•  Re peat sa m ples ma y be t a ke n f or t ec h nical iss ues a n d u nsc he d ule d s a m ples or assess me nts ma y 
be ta ke n f or safet y reas o ns. Please refer t o A p p e n di x 2, Secti o n 1 0. 2  f or f urt her details o n 
la b orat or y sa m ples. 
•  T he i n vesti gat or or site  st aff m ust i nf or m s u bjects a b o ut s y m pt o ms of h y p o gl ycae mia.  
8. 1  
Effic ac y assess me nts   
Pla n ne d ti me p oi nts f or all efficac y asse ss me nts are pr o vi de d i n t he fl o w c hart (see Secti o n 1. 2 ). 
8. 1. 1  
B o d y me as ure me nts  
•  B o d y wei g ht will be meas ure d a n d rec or de d as s p ecifie d i n t he fl o wc hart (see Secti o n 1. 2 ). 
B o d y wei g ht m ust be meas ure d o n a di gital sc ale. T he cali brati o n sta n dar d s h o ul d prefera bl y be 
o nce yearl y or reflect t he c o u ntr y re q uir e me nts. T he sa me scale m ust be us e d t hr o u g h o ut t he 
trial. Meas ure m e nt m ust be perf or me d wit h o ut s h oes, o n a n e m pt y bla d der a n d o nl y weari n g 
li g ht cl ot hi n g a n d rec or de d i n t he e C R F i n kil o gra m [ k g] or p o u n ds [l b] wit h t he precisi o n of 
1/ 1 0 u nit (e. g. 7 5. 3 k g / 1 6 6. 0 l b).  
•  Hei g ht is meas ure d wit h o ut s h oes i n ce nti metres or i nc hes ( o ne deci mal). B MI will be 
calc ulate d b y t he C R F fr o m scree ni n g dat a a n d m ust be i n a gree m e nt wit h i ncl usi o n criteri o n 
n o. 3.  
•  Waist circ u mfere n ce will be meas ur e d a n d rec or de d as s pecifie d i n t he fl o wc hart (see 
Secti o n  1. 2 ). T he meas ure me nt of waist cir c u mfere nce s h o ul d be p erf or me d usi n g t he 
n o n -stretc ha ble m eas uri n g ta p e pr o vi de d b y N o v o N or dis k a n d rec or de d i n t he e C R F t o t he 
nearest c m or i nc h. Waist circ u mfere nce  is defi ne d as t he mi ni mal a b d o mi nal circ u mf ere n ce 
l ocate d mi d wa y bet w ee n t he l o wer ri b mar gi n a n d t he iliac crest. Meas ure m e nt m ust be 
perf or me d i n a sta n di n g p ositi o n w hile t he s u bject is breat hi n g n or m all y. T he meas uri n g ta pe 
s h o ul d t o uc h t he s ki n b ut not c o m press s oft tiss ue a n d t wists i n t he ta pe s h o ul d be a v oi de d.  
8. 1. 2  
Cli nic al effic ac y l a b or at or y assess me nts  
•  All pr ot oc ol -re q uir e d la b orat or y assess me nts, as defi ne d i n A p pe n di x 2, Secti o n  1 0. 2 , m ust be 
c o n d ucte d i n acc or da nce wit h t he fl o wc hart a n d t he la b orat or y m a n ual.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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5 9
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
6 0  of 1 1 6  
 
8. 2  
S afet y assess me nts   
Pla n ne d ti me p oi nts f or all safet y assess me nts are pr o vi de d i n t he fl o wc h art (see Secti o n 1. 2 ).  
A c o nc o mit a nt ill ness  is a n y ill ness t hat is alr ea d y prese nt at t he ti me p oi nt fr o m w hic h A Es are 
c ollecte d or f o u n d as a res ult of a scree ni n g pr oce d ure or ot her trial pr oce d ures perf or me d bef ore 
e x p os ure t o trial pr o d uct.   
Me dic al hist or y is a me dical e ve nt t hat t he s u bject e x perie nce d pri or t o t he ti me p oi nt fr o m w hic h 
A Es are c ollecte d.  
O nl y rele va nt a n d si g nifi ca nt me dical hist or y as j u d ge d b y t h e i n vesti gat or m ust be rec or de d i n t he 
Me dical hist or y/ C o nc o mita nt ill ness f or ms i n t he e C R F acc or di n g t o t he fl o wc hart (s ee 
Sec ti o n 1. 2 ). Rele va nt m e dical hist or y i ncl u des, b ut is n ot li mite d t o, C O VI D-1 9 a n d t he f oll o wi n g 
pre -s pecifie d diseas e classes: 
•  Breast ne o plas m  
•  S ki n c a ncer a n d s ki n dis or der  
•  Gastr oi ntesti nal dis or der a n d ne o plas m  
•  Gall bla d der disease a n d pr oce d ure  
•  Pa ncreatic dis ease  
•  Car di o vasc ular dis or d er  
•  Ps yc hiatric dis or d er  
•  Wei g ht dis or der  
If t he fiel d is left bla n k i n t he e C R F it will be i nter prete d as if t he s u bj ect di d n ot ha ve a hist or y of 
t he pre-s pecifie d dise ase classes at scree ni n g. 
Wei g ht hist or y a n d ris k fact ors f or pre -s p ecifie d ca ncer t y p es m ust be rec or de d i n t he Ris k Fact ors 
a n d Wei g ht Hist or y e C R F acc or di n g t o t he fl o wc hart (see Secti o n 1. 2 ) a n d i ncl u des: 
 
•  Wei g ht hist or y (i n cl u di n g pre vi o us wei g ht, de b ut ti me of o ver wei g ht, pr e vi o us wei g ht l oss 
atte m pts, pre vi o us use of a nti -o besit y prescri pti o n me dicati o n, c o nsi derati o ns re gar di n g b ariatric 
s ur ger y, a n d fa mil y hist or y of o ver wei g ht/ o besit y) 
•  Ris k fact ors f or breast (f or fe male s u bjects o nl y), c ol o n a n d s ki n ca ncer (i n cl u di n g fa mil y 
hist or y of breast, c ol o n a n d/ or s ki n ca ncer a n d a ge at ti me of dia g n osis f or rele va nt fa mil y 
me m bers, pre dis p osi n g fact ors f or breast a n d s ki n ca ncer, me narc h e/ me n o pa use, breast ca n cer 
scree ni n g, h or m o n e re pl ace me nt t hera p y) 
I n case of a n a b n or mal a n d cli nicall y si g nifica nt fi n di n g f ulfilli n g t he defi niti o n of a c o nc o mita nt 
ill ness or me dical histor y, t he i n vesti gat or m ust rec or d t he fi n di n g o n t he Me dical Hist or y  / 
C o nc o mita nt Ill ness f or m.  
8. 2. 1  
Me nt al He alt h i nstr u me nts  
•  P H Q -9 4 1 is a 9-ite m de pressi o n m o d ule of t he patie nt healt h q uesti o n naire, w hic h is a 
self-a d mi nistere d dia g n ostic t o ol use d f or assess m e nt of me ntal dis or ders. T he q uesti o n naire 
will be a vaila ble i n a li n g uisticall y vali date d tra nslate d versi o n.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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1
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 of
  Pr ot oc ol  versi o n 4. 0
6 0
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
6 1  of 1 1 6  
 
•  C -S S R S 4 2 is a detaile d q uesti o n naire assessi n g b ot h s uici dal be ha vi o ur a n d s uici dal i deati o n. 
T he q uesti o n naire will be a d mi nistere d as a n i nter vie w b y t h e i n vesti gat or or a q ualifie d 
dele gate. T he q uesti o n naire ( C-S S R S Baseli ne a n d C -S S R S Si nce Last Visit) will be a vaila ble 
i n a li n g uisticall y v ali dat e d tra nslate d v ersi o n. 
•  Pri or t o a d mi nisteri n g t h e C -S S R S q uesti o n naire, t he i n vesti gat or or q ualifi e d dele gat e m ust 
c o m plete s ufficie nt tr ai ni n g.  
If a s u bject h as a P H Q -9 sc ore of 1 0 -1 4 b ot h i ncl usi ve t he s u bject s h o ul d be referre d t o a me ntal 
healt h pr ofessi o nal ( M H P) if j u d ge d rele va nt b y t he i n vesti gat or. If referral is n ot dee me d rele va nt 
t his, al o n g wit h t he reas o n w h y, m ust be d oc u me nte d i n t he s u bject’s me dical rec or ds. 
A s u bject m ust be referre d t o a M H P if:  
•  t he s u bject has a P H Q-9 sc ore ≥1 5 or  
•  t he s u bject has a n y s uici d al be ha vi o ur or 
•  t he s u bject has a n y s uici d al i deati o n of t y p e 4 or t y pe 5 o n a n y C-S S R S assess me nt or  
•  i n t he o pi ni o n of t he i n vesti gat or, it is necess ar y f or t he safet y of t he s u bject  
If o ne or m ore of t he referral criteria are met, t he i n vesti gat or s h o ul d e x plai n t o t he s u bject w h y t h e 
referral a n d ps yc hiatric e val uati o n b y a M H P is nee de d. If t h e s u bject r ef uses t o be referre d t o a 
M H P, t he s u b ject’s decisi o n s h o ul d be d oc u me nte d i n s u bject’s me dical r ec or d a n d t he i n vesti gat or 
m ust assess if it is safe f or t he s u bject t o c o nti n ue i n t he trial or if t he s u bject s h o ul d be disc o nti n ue d 
fr o m trial pr o d uct. 
If a s u bject’s ps yc hiatric dis or der ca n b e a d e q uatel y treate d wit h ps yc h ot hera p y a n d/ or 
p har mac ot hera p e utic treat me nt, t he n t he s u bject, at t he discreti o n of t he i n v esti gat or (a n d i n 
a gree m e nt wit h t he M H P), ma y c o nti n ue i n t he tri al. Ot her wise, t he s u bject m ust be disc o nti n ue d 
fr o m trial pr o d uct d ue t o safet y c o n cer n as j u d ge d b y t he i n vesti gat or.  
8. 2. 2  
P h ysic al e x a mi n ati o ns  
•  A p h ysic al e x a mi nati o n will i ncl u de assess me nts of t he breast, hea d (ears, e yes, n ose, t hr o at a n d 
nec k), res pirat or y -, car di o vasc ular -, gastr oi ntesti nal (i ncl u di n g m o ut h) -, m usc ul os keletal - a n d 
ce ntral a n d p eri p heral ner v o us s yste m, s ki n, ge n eral a p peara nce, l y m p h n o de pal pati o n, t h yr oi d 
gla n d a n d a b d o me n. as s pecifie d i n t he Fl o wc hart (see Secti o n  1. 2 ). 
•  I n v esti gat ors s h o ul d pa y s pecial atte nti o n t o cli nical si g ns relate d t o pre vi o us seri o us ill nesses. 
8. 2. 3  
Vit al si g ns  
•  P ulse rate, res pir at or y rat e, o x y ge n sat ur ati o n ( Sa O 2) as well as s yst olic a n d diast olic bl o o d 
press ure will be assesse d.  
•  Vital si g n assess me nt s h o ul d be prece de d b y at least 5 mi n utes of rest f or t he s u bject i n a q uiet 
setti n g wit h o ut distracti o ns (e. g., n o use of tel e visi o n, cell p h o nes).  
•  Bl o o d press ur e a n d p ulse rate meas ure me nts will be assesse d sitti n g wit h a c o m pletel y 
a ut o mate d de vice. Ma n u al tec h ni q ues m ust be use d o nl y if a n a ut o mate d de vice is n ot a vaila ble.  
•  Bl o o d press ur e will c o nsist of 3 s yst olic a n d diast olic bl o o d press ure meas ure me nts wit h 
i nter vals of at least 1-2 mi n utes. A n a d diti o nal f o urt h bl o o d  press ure meas ure me nt m ust be 
perf or me d if t he first t w o rea di n gs o n s yst olic or diast olic bl o o d press ure differ b y > 1 0 m m H g. 
S yst olic bl o o d press ure is t o be rec or de d as t he m ea n of t he last 2 s yst olic bl o o d press ure 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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V V- T M F- 5 0 4 2 3 4 5
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6 1
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
6 2  of 1 1 6  
 
rea di n gs, a n d diast olic bl o o d press ure as t he mea n of t he last 2 diast olic bl o o d press ure rea di n gs  
i n t he e C R F. T he e C R F will calc ulate t he mea n of t he last 2 s yst olic bl o o d press ure rea di n gs  a n d 
t he mea n of t he last 2 diast olic bl o o d press ure rea di n gs. 
•  P ulse rate will be meas ur e d i n c o n necti o n t o t he bl o o d press ure meas ure m e nts. Rec or d t he p ulse 
rate f or t h e last 2 bl o o d press ure meas ure m e nts i n t he e C R F. T he e C R F will calc ulate t he mea n 
of t he last 2 p ulse meas ur e me nts.  
8. 2. 4  
Electr oc a r di o gr a ms  
•  1 2 -lea d E C G will be o btai ne d as o utli ne d i n t he fl o wc hart usi n g a n E C G mac hi ne t hat 
a ut o maticall y calc ulat es t he heart rate a n d meas ures P R, Q R S, Q T a n d Q Tc i nter vals. 
P art 1  o nl y :  
•  At visits w here P K sa m ples are c ollecte d t he E C G rec or di n gs m ust be perf or me d pri or t o P K 
sa m ple c ollecti on  
•  At eac h  visit w here a n  E C G assess me nt  is sc he d ule d, t hree c o ns ec uti ve E C G rec or di n gs m ust be 
perf or me d after t he s u bject has bee n place d i n a s u pi ne p ositi o n f or a least 1 0 mi n utes. T he 
E C Gs will be st ore d f or p ote nti al f ut ure res earc h. 
•  All ori gi nal E C G rec or di n gs , i ncl u di n g electr o nic versi o ns,  m ust be  ke pt at site f or t he d urati o n 
of t he trial.   
P art 2 o nl y:  
•  At visits w here P K sa m ples are c ollecte d t he E C G rec or di n gs m ust be perf or me d pri or t o P K 
sa m ple c ollecti o n 
8. 2. 5  
Cli ni c al s af et y l a b or at or y assess me nts  
All pr ot oc ol -re q uir e d la b orat or y assess me nts, as defi ne d i n A p pe n di x 2, Secti o n 1 0. 2 , m ust be 
c o n d ucte d i n acc or da nce wit h t he la b orat or y ma n ual a n d t he pr ot oc ol fl o w c hart . 
8. 2. 5. 1  
Uri ne s a m ples  
Uri n al ysis  
Uri nal ysis m ust be c o n d u cte d i n acc or da n ce wit h t he fl o wc hart a n d as d efi n e d i n  A p pe n di x 2, 
Secti o n 1 0. 2 . 
2 4 -h o ur uri ne c ollecti o n  
All s u bjects m ust recei ve a c o ntai ner f or uri n e c oll ecti o n, a n d i nstr ucti o ns ( ver bal a n d i n writi n g) i n 
h o w t o c ollect t he uri ne at h o me. T he c ollecti o n m ust be c o n d ucte d i n acc or da nce wit h t he 
fl o wc hart. T h e c ollect e d uri ne s h o ul d be st ore d i n a c ol d place d uri n g t he c ollecti o n peri o d. T he 
s u bjects will be as ke d t o meas ure a n d rec or d t he fl ui d inta ke ( m L) i n t he diar y.  
S u bjects s h o ul d ha ve a n e m pt y bla d d er (after m or ni n g v oi d) w he n t he uri n e c ollecti o n ti me starts 
a n d be e n c o ura ge d t o uri nate at t he e n d of t he c oll ecti o n ti me ( m ust i ncl u de m or ni n g v oi d).  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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V V- T M F- 5 0 4 2 3 4 5
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1
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 of
  Pr ot oc ol  versi o n 4. 0
6 2
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
6 3  of 1 1 6  
 
T he uri ne c ollecte d d uri n g t he 2 4 -h o ur pe ri o d will be p o ole d a n d t he t otal v ol u me will be 
deter mi ne d a n d assesse d b y t he ce ntral la b orat or y.  
Start a n d st o p date of uri ne c ollecti o n a n d ti me (st art -a n d e n d ti me) of t he 2 4 -h o ur peri o d m ust be 
re p orte d i n t he e C R F. 
T he uri nal ysis a n d 2 4 -h o ur uri ne c ollecti o n will be a nal yse d f or t he f oll o wi n g para meters:  
Assess me nt  
Uri n al ysis  
2 4 -h o ur uri ne  
Calci u m  
X  
X  
S o di u m  
X  
X  
P otassi u m  
X  
X  
C ortis ol, free  
X  
X  
Creati ni ne  
X  
X  
Al b u mi n  
X  
X  
C ortis ol/ Creati ni ne  
X  
X  
Al b u mi n/ Creati ni ne  
X  
X  
Ne utr o p hil gelacti nas e -assoc iate d 
li p ocali n/ Creati ni ne 
X  
  
V ol u me  
 
X  
Creati ni ne Cleare nce  
 
X  
8. 2. 6  
I njecti o n site re acti o ns 
I nje cti o n site reacti o ns will be assesse d b y t he i n v esti gat or as o utli ne d i n t he fl o wc hart. All i njecti o n 
site reacti o ns will be re p orte d as A Es. All i njecti o n site reacti o ns relate d t o t he sa me i njecti o n will 
be re p ort e d as o ne A E wit h start a n d st o p date c o v eri n g t h e first a p p eara nce a n d last disa p peara nce 
of a n y l ocal s y m pt o ms or l ocal o bjecti ve si g ns. A d diti o nal i nf or mati o n a b o ut t he i njecti o n s ite 
reacti o n, i.e., l oc al s y m pt o ms a n d/ or l ocal o bjecti v e si g ns, m ust be pr o vi de d i n t he e C R F i njecti o n 
site reacti o n f or m. 
A d diti o nal assess me nts will be perf or me d u ntil r es ol uti o n, as j u d ge d n ecessar y b y t he i n vesti gat or.  
8. 3  
A d verse e v e nts a n d seri o us a d verse e ve nts  
T he i n vesti gat or is res p o nsi ble f or detecti n g, d oc u me nti n g, rec or di n g a n d f oll o wi n g u p o n e ve nts 
t hat meet t he defi niti o n of a n A E or S A E or all t he e ve nts liste d bel o w:  
•  S A Es  
•  F oll o wi n g A Es irres p ecti ve of seri o us n ess  
•  A Es lea di n g t o disc o nti n uati o n of trial pr o d uct  
•  A Es wit h a d diti o nal data c ollecti o n ( please refer t o Ta ble  8 -1 ) 
•  Pre g n a ncies a n d pre g n a n c y -rel ate d A Es 
•  Tec h nical c o m plai nts  
T he defi niti o n of A Es a n d S A Es ca n be f o u n d i n A p pe n di x 3, Secti o n 1 0. 3. 1  a n d 1 0. 3. 2 , al o n g wit h 
a descri pti o n of A Es re q uiri n g a d diti o nal data c ollecti o n.  
S o me A Es re q uire a d diti o nal data c ollecti o n o n a s pecific e v e nt f or m. T his al wa ys i ncl u des 
me dicati o n err or, mis use a n d a b use of I M P. T he rele va nt e ve nt(s) are liste d bel o w i n Ta ble  8 -1 . 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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1
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 of
  Pr ot oc ol  versi o n 4. 0
6 3
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
6 4  of 1 1 6  
 
T a ble  8 -1  
A Es re q uiri n g a d diti o n al d at a c ollecti o n (seri o us a n d n o n -seri o us A Es) 
E ve nt t y pe   
A E re q uiri n g a d diti o n al d at a c ollecti o n  
Me dicati o n err or  
X  
Mis use a n d a b use  
X  
Ac ute gall bla d der disease  
X  
He p atic e ve nt  
X  
Mali g na nt ne o plas m  
X  
Ac ute pa ncreatitis  
X  
Ac ute ki d ne y i nj ur y  
X  
I nj ecti o n site reacti o ns 
X  
* A d diti o nal data f or mis use or a b use of trial pr o d uct is re p orte d o n t he me dicati o n err or e ve nt f or m.  
A detaile d descri pti o n of t he e ve nts me nti o ne d i n t he a b o ve ta bl e ca n b e f o u n d i n A p pe n di x 3, 
Secti o n 1 0. 3. 3 . 
8. 3. 1  
Ti me peri o d a n d fre q ue nc y f or c ollecti n g A E a n d S A E i nf or m ati o n  
All A Es a n d S A Es m ust be c ollecte d fr o m t he ra n d o misati o n visit a n d u ntil t he e n d of trial visit at 
t he ti me p oi nts s pecifie d in t he fl o wc hart.  
Me dical occ urre n ces t hat ta ke place or ha v e o nset pri or t o t he ti me p oi nt fr o m w hic h A Es are 
c ollecte d will be rec or de d as c o nc o mita nt ill ness/ me dical hist or y. A E a n d S A E re p orti n g ti meli nes 
ca n be f o u n d i n A p pe n di x 3, Secti o n 1 0. 3 . All S A Es m ust be rec or de d a n d re p orte d t o 
N o v o  N or dis k or desi g nee wit hi n 2 4 h o urs, a n d t he i n vesti gat or m ust s u b mit a n y u p dat e d S A E data 
t o N o v o N or dis k wit hi n 2 4 h o urs of it bei n g a vail a ble.  
I n v esti gat ors are n ot o bli gat e d t o acti vel y see k f or A E or S A E i n f or mer trial s u bjects. H o we v er, if 
t he i n vesti gat or l ear ns of a n y S A E, i n cl u di n g a d eat h, at a n y ti me after a s u bject has bee n 
disc o nti n ue d fr o m/c o m plete d t he trial, a n d t he i n v esti gat or c o nsi ders t he e v e nt t o be 
p ossi bl y/ pr o ba bl y rel ate d t o t he trial pr o d uct or relate d t o trial partici pati o n, t he i n vesti gat or m ust 
pr o m ptl y n otif y N o v o N or dis k.  
8. 3. 2  
Met h o d of detecti n g A Es a n d S A Es  
T he met h o d of re c or di n g, e val uati n g, a n d ass essi n g ca usalit y of A E a n d S A E a n d t he pr oce d ures f or 
c o m pleti n g a n d tr a ns mitti n g S A E re p orts are pr o vi de d i n A p pe n di x 3, Secti o n 1 0. 3 . 
Care s h o ul d be ta ke n n ot t o i ntr o d uce bias w he n d etecti n g A Es a n d/ or S A Es. O pe n -e n d e d a n d 
n o n -lea di n g ver bal q uesti o ni n g of t he s u bject is t he preferre d met h o d t o i n q uire a b o ut e ve nts. 
8. 3. 3  
F oll o w -u p of A Es a n d S A Es  
After t he i nitial A E/ S A E re p or t, t he i n vesti gat or is re q uire d t o pr o acti vel y f oll o w eac h s u bject at 
s u bse q ue nt visits/c o ntacts. All S A Es, s h o ul d be f oll o we d u ntil fi nal o utc o me of t he e v e nt or t he 
s u bject is l ost t o f oll o w-u p as descri be d i n Secti o n 7. 3 . F urt her i nf or mati o n o n f oll o w-u p a n d fi nal 
o utc o me of e ve nts is gi ve n i n A p pe n di x 3, Secti o n  1 0. 3 . 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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1
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 of
  Pr ot oc ol  versi o n 4. 0
6 4
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
6 5  of 1 1 6  
 
8. 3. 4  
Re g ul at or y re p orti n g re q uire me nts f or S A Es  
Pr o m pt n otificati o n b y t he i n vesti gat or t o N o v o N or dis k or desi g n ee of a n  S A E is esse ntial s o t hat 
le gal o bli gati o ns a n d et hical res p o nsi bilities t o war ds t he safet y of s u bjects a n d t he safet y of a trial 
pr o d uct u n der cli nical i n vesti gati o n are met.  
N o v o N or dis k has a le gal res p o nsi bilit y t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d ot her 
re g ulat or y a ge ncies a b o ut t he safet y of a trial pr o d uct u n der cli nical i n vesti gati o n. N o v o N or dis k 
will c o m pl y wit h c o u ntr y -s pecific re g ulat or y re q uire me nts relati n g t o safet y re p orti n g t o t he 
re g ulat or y a ut h orit y, I R B/I E C, a n d i n vesti gat ors. T his als o i ncl u des s us pecte d u ne x pecte d seri o us 
a d verse reacti o ns ( S U S A R). A n i n vesti gat or w h o recei v es a n i n vesti gat or s afe t y re p ort descri bi n g 
a n S A E or ot her s pecific safet y i nf or mati o n ( e. g. , s u m mar y or listi n g of S A Es) fr o m N o v o N or dis k 
will re vie w a n d t he n file it al o n g wit h t he I n vesti gat or’s Br oc h ure a n d will n otif y t he I R B/I E C, if 
a p pr o priate acc or di n g t o l ocal re q uir e me nts.  
8. 3. 5  
Pre g n a nc y  
Details of pre g n a ncies i n fe male s u bjects a n d if i n dicate d , fe m ale part n ers of male s u bjects will be 
c ollecte d after first e x p os ure t o trial pr o d uct.  
If a fe male s u bject bec o mes pre g na nt, t he i n vesti gat or s h o ul d i nf or m N o v o N or dis k wit hi n 
1 4  cale n dar da ys of lear ni n g of t he pre g na n c y a n d s h o ul d f oll o w t he pr oce d ures o utli ne d i n 
A p pe n di x  4, Secti o n 1 0. 4 . 
If a fe male part ner of a m ale s u bject bec o mes pre g na nt a n d t he o utc o me of t he pre g na n c y is 
a b n or mal, t he i n vesti gat or s h o ul d i nf or m N o v o N or dis k wit hi n 1 4 cale n dar da ys of lear ni n g of t he 
a b n or mal o utc o me a n d s h o ul d f oll o w t he pr oce d ures o utli ne d i n A p pe n di x 4 , Secti o n 1 0. 4 . 
8. 3. 6  
Tec h nic al c o m pl ai nts  
Tec h nical c o m plai nts will be c ollecte d f or all pr o d ucts liste d o n t he tec h nical c o m plai nt f or m.  
I nstr u cti o ns f or re p ortin g tec h nical c o m plai nts ca n be f o u n d i n A p pe n di x 5, Secti o n 1 0. 5 . 
I n or der f or N o v o N or dis k t o perf or m a c o m plete i n vesti gati o n of re p orte d S A Es, N o v o N or dis k 
mi g ht as k t he i n vesti gat or t o c o m plete a tec h nical c o m plai nt f or m.  
8. 4  
Tre at me nt of o ver d ose  
A n y d os e of N N C 0 1 6 5 -1 8 7 5 or se ma gl uti de ≥ 1 pe n u nit of pla n ne d trial pr o d uct d ose i n trial 4 7 0 8 
will be c o nsi dere d a n o ver d ose.  
Per t he c ut-off date t her e are n o re p orts of o v er d ose of N N C 0 1 6 5 -1 8 7 5 3 6. 
O ver d oses wit h se ma gl uti de of u p t o 4 m g i n a si n gle d ose, a n d u p t o 4 m g i n a wee k h a ve bee n 
re p orte d i n cli nical tri als. T he m ost c o m m o nl y re p orte d A E was n a usea. All s u bjects rec o v ere d 
wit h o ut c o m plicati o ns.  
Acci de ntal o v er d ose m u st be re p orte d as a me dicati o n err or. I nte nti o nal o v er d ose m ust be re p orte d 
as mis use a n d a b use, ple ase refer t o A p p e n di x 3, Secti o n 1 0. 3  f or f urt her details. 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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1
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 of
  Pr ot oc ol  versi o n 4. 0
6 5
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
6 6  of 1 1 6  
 
T here are n o s p ecific a nti d otes f or o ver d ose wit h se ma gl uti de or N N C 0 1 6 5 -1 8 7 5. I n t h e e ve nt of a n 
o ver d ose, a p pr o priate s u p p orti ve treat me nt s h o ul d be i nitiate d acc or di n g t o t he s u bject’s cli nical 
si g ns a n d s y m pt o ms. 
I n t he e ve nt of a n o ver d ose, t he i n vesti gat or s h o ul d cl osel y m o nit or t he s u bject f or o ver d ose-relate d 
A E/ S A E s. A pr ol o n ge d p eri o d of o bser vati o n a n d treat me nt f or t hes e s y m pt o ms ma y be n ecess ar y, 
ta ki n g i nt o acc o u nt t he l o n g half -lives  of se ma gl uti de a n d N N C 0 1 6 5 -1 8 7 5 of a p pr o xi matel y 
1  wee k.  
Decisi o ns re gar di n g d ose i nterr u pti o ns or m o dificati o ns will be ma de b y t h e i n vesti gat or base d o n 
t he cli nical e val uati o n of t he s u bject. 
F or m ore i nf or mati o n o n o ver d ose, c o ns ult t he c urre nt I n vesti gat or’s Br oc h ures f or N N C 0 1 6 5 -1 8 7 5 
or se ma gl uti de 3 6, 3 8 a n d a n y u p dat es here of a n d/ or c o ntact N o v o N or dis k.  
8. 5  
P h ar m a c o ki netics  
•  Bl o o d sa m ples f or me as uri n g plas ma c o nce ntrati o n of N N C 0 1 6 5 -1 8 7 5 a n d se ma gl uti de will be 
dra w n f or all s u bjects o n visits s pecifie d i n t he fl o wc hart (s ee Secti o n 1. 2 ) a n d i n A p pe n di x 2, 
Secti o n  1 0. 2 .  
•  A t visits w here I M Ps are a d mi nistere d, t he P K sa m ples m ust be c ollecte d pre-d ose . 
•  T he e x act ti mi n g  ( date a n d ti me) of trial pr o d uct d ose m ust be rec or de d i n t he diar y b y t he 
s u bject a n d tra nscri be d i nt o t he e C R F. 
•  T he p ur p ose of m eas uri n g plas ma N N C 0 1 6 5 -1 8 7 5 a n d se ma gl uti de le vels is t o perf or m 
p har mac o ki netic a nal yses a n d t o assess p ote ntial dr u g i nter fere nce wit h a nti b o d y a nal yses.  
•  Bl o o d sa m ples will be us e d t o e val uate t he p har m ac o ki netics a n d s afet y of c o -escalati o n of 
N N C 0 1 6 5 -1 8 7 5 a n d se m a gl uti de. I n Part 1, N N C 0 1 6 5 -1 8 7 5 bi oa nal yti cal res ults ( P K data) will 
be a nal yse d a n d e val u ate d o n a n o n g oi n g b asis b y a n i nter nal N o v o N or dis k safet y o versi g ht 
gr o u p acc or di n g t o ‘t he i nter nal N o v o N or dis k safet y o v ersi g ht gr o u p c hart er’.  
•  Bl o o d sa m ples f or P K assess me nts m ust be c ollecte d, ha n dle d a n d s hi p pe d acc or di n g t o t he 
descri pti o n i n t he la b orat or y ma n u al s u p plie d b y t he ce ntr al la b orat or y. T h e bi oa nal ysis of 
N N C 0 1 6 5 -1 8 7 5 a n d se m a gl uti de plas ma c o nce ntr ati o ns will be perf or me d b y s pecial 
la b orat ories. D etails of t he bi oa nal ysis will be o utli ne d i n a bi oa nal ytical st u d y pla n iss ue d b y 
t he s pecial la b orat ories. Bi oa nal ysis of plas ma s a m ples f or N N C 0 1 6 5-1 8 7 5 a n d se ma gl uti de 
c o nce ntr ati o ns will be carrie d o ut usi n g v ali date d L C -M S/ M S assa ys.  
•  Eac h plas ma sa m ple will be di vi de d i nt o 2 ali q u ots (e. g. , o ne f or p har m ac o ki netics a n d a 
bac k u p). Plas ma sa m ples ma y als o b e use d t o e val uate safet y or efficac y as pects t hat a d dress 
c o ncer ns arisi n g d uri n g or after t h e trial. Resi d ual sa m ple material ma y be use d f or e x pl orat or y 
i n vesti gati o n of meta b olites a n d bi oa nal ysis assa y de vel o p me nt a n d tr o u bles h o oti n g i n relati o n 
t o t he p har mac o ki netic assa y. P ote ntial meta b olite a nal ysis will be re p orte d se parat el y fr o m t he 
C T R. Bac k u p sa m ples will be st ore d at t he ce ntral la b orat or y u ntil fi nal Cli nical Trial Re p ort 
( C T R) i n case N o v o N or dis k re q uests f urt her a nal ysis of t he P K sa m ples. 
8. 6  
P h ar m a c o d y n a mi cs  
N ot a p plica ble i n t his trial.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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1
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 of
  Pr ot oc ol  versi o n 4. 0
6 6
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
6 7  of 1 1 6  
 
8. 7  
Ge neti cs  
Ge netic sa m ples ma y b e c ollecte d f or f ut ure a nal yses. Refer t o Secti o n 8. 9  f or f urt her details a n d 
A p pe n di x 8, Secti o n 1 0. 8  for st ora ge.  
8. 8  
Bi o m ar kers  
C ollecti o n of sa m ples f or bi o mar ker researc h is part of t his trial . T he f oll o wi n g sa m ples are re q uire d 
a n d will be c ollecte d fr o m all s u bjects i n t his trial:  
•  Bi o mar kers li n ke d t o h u n ger a n d satiet y:  
•  S ol u ble Le pti n Rece pt or  
•  Le pti n  
•  Bi o mar kers li n ke d t o safet y m o nit ori n g : 
•  Pr ostate S pecific A nti ge n ( P S A)  
T he assa ys use d f or S ol u ble L e pti n R ece pt or a n d L e pti n are f or res earc h us e o nl y, t hes e res ults will 
be re p ort e d directl y t o N o v o N or dis k.  
8. 9  
Bi os a m ples f or f ut ure rese arc h  
C ollecti o n of bi osa m ples f or f ut ure a nal ysis is a c o m p o ne nt of t his trial. T he sa m ples will be st ore d 
i n a bi o ba n k a n d all o w f or f ut ure a n al yses of bi o m ar kers, b ot h ge netic a n d circ ulati n g bi o mar kers, 
w he n ne w k n o wl e d ge or i m pr o ve d testi n g tec h n ol o gies ma y h a ve bec o me a vaila ble d uri n g or after 
t he trial. Partici pati o n is o pti o nal, a n d s u bjects m ust si g n a se p arate i nfor me d c o nse nt t o i n dicate 
t heir partici pati o n i n t he bi o ba n k c o m p o ne nts of t he trial. S u bjects w h o d o n ot wis h t o partici pate i n 
t he bi o ba n k c o m p o ne nts ma y still partici pate i n t h e trial. F or t h e bi o ba n k, bl o o d sa m ples will be 
c ollecte d acc or di n g t o Secti o n 1 0. 8  a n d st ore d f or f ut ure use.  
Ge netic a n al ys es ma y i ncl u de a nal ysis of selecte d ge n es or ge n etic mar k ers t hr o u g h o ut t he ge n o m e 
wit h t he p ur p ose of u n dersta n di n g a n d pre dicti n g res p o nse t o se ma gl uti de a n d N N C 0 1 6 5 -1 8 7 5  as 
well as t o u n dersta n d o besit y or ot her relate d c o n diti o ns.  
A nal ys es of cir c ulati n g bi o mar kers will meas ure h or m o nes, meta b olites or ot her n o n -ge n etic ser u m 
e ntities wit h t he p ur p os e of u n dersta n di n g a n d pre dicti n g res p o ns e t o se ma gl uti de a n d 
N N C 0 1 6 5 -1 8 7 5 as well as u n dersta n di n g o besit y or ot her rel ate d c o n diti o ns.  
T he sa m ples ma y be a nal ys e d as part of a m ulti -trial assess me nt. 
Res ults will n ot be part of t he C T R. T he pri mar y o bjecti ve of t he a n al yses is t o i n vesti gate o n a 
p o p ulati o n le vel a n d res ults are ver y u nli kel y t o ha ve cli nical utilit y o n a n i n di vi d ual le vel. 
F urt her m ore, t he a n al yses will be d o ne o n pse u d o -a n o n y mis e d data. T heref ore n o res ults fr o m 
a nal ysis p erf or me d o n t hese sa m ples will be re p orte d t o sites or trial s u bjects. M ore o ver, n o dat a 
a nal ysis or p u blicati o ns will be perf or me d o n p atie nt i de ntifia ble data.  
T he bi o ba n k sa m ples will be st ore d u p t o 1 5 years after t he tri al has re p orte d at an a p pr o priate l o n g 
ter m st ora ge facilit y (see A p pe n di x 8, Secti o n 1 0. 8 ). 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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1
 |
 of
  Pr ot oc ol  versi o n 4. 0
6 7
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
6 8  of 1 1 6  
 
8. 1 0  I m m u n o ge nicit y assess me nts 
Bl o o d sa m ples t o be a n al ys e d f or a nti b o dies a gai n st N N C 0 1 6 5-1 8 7 5 will be dra w n at pre -s p ecifie d 
ti me p oi nts acc or di n g t o t he fl o w c hart (see Secti o n 1. 2 ). F or details o n bl o o d sa m pli n g, ser u m 
pre parati o n a n d st ora ge, please refer t o t he la b orat or y ma n ual.  
T he i n vesti gat or will n ot be a ble t o re vi e w t he res ults of a nti b o d y meas ure me nts i n relat i o n t o A Es 
as t hese are a n al ys e d aft er e n d of trial.  
Assess me nt of a nti b o dies a gai nst N N C 0 1 6 5 -1 8 7 5 will be perf or me d b y N o v o N or dis k usi n g 
vali date d assa ys de v el o p e d b y N o v o N or dis k t o s pecificall y det er mi ne a nti b o d y le vels a gai nst 
N N C 0 1 6 5 -1 8 7 5 a n d t o f urt her c h aracterise t he a nti b o dies wit h res pect t o cr oss -reacti vit y a n d 
ne utralisi n g effect.  
•  All sa m ples will be scree ne d f or a nti -N N C 0 1 6 5 -1 8 7 5 a nti b o dies.  
•  Sa m ples c o nfir me d p ositi ve f or a nti b o dies a gai nst N N C 0 1 6 5 -1 8 7 5 will be f urt her c h aracterise d 
f or cr oss reacti vit y t o P Y Y3 -3 6. 
•  Sa m ples c o nfir me d cr oss -reacti ve t o P Y Y3 -3 6 at t he E n d of Trial visit ( V 1 7  f or Part 1  a n d V 1 9 
f or Part 2) will be f urt her c haracterise d f or ne utralisi n g effect a gai nst P Y Y 3 -3 6. 
•  T he ne utralisi n g effect of a nti -N N C 0 1 6 5 -1 8 7 5 a nti b o dies will als o be e val u ate d b y c orrelati o n 
t o P K/ P D. 
A detaile d descri pti o n of t he assa y met h o d will be i ncl u de d i n a n a nal ytical re p ort. A nti b o d y assa ys 
will be vali date d acc or di n g t o i nter nati o nal g ui deli nes a n d rec o m me n dati o ns.  
At t he e n d of t he trial, t h e f oll o wi n g d ata will be electr o nicall y tra nsferre d t o t he N o v o N or dis k 
data base:  
•  A nti -N N C 0 1 6 5 -1 8 7 5 bi n di n g a nti b o dies ( p os/ ne g a n d titre)  
•  A nti -N N C 0 1 6 5 -1 8 7 5 bi n di n g a nti b o dies cr oss -reacti n g wit h P Y Y3 -3 6 ( p os/ ne g) 
•  A nti - P Y Y 3 -3 6 ne utralisi n g a nti b o dies ( p os/ ne g)  
Resi d ual a nti b o d y sa m pl es will be retai ne d ( pleas e refer t o A p pe n di x 8, Secti o n 1 0. 8 ). 
Se vere h y pers e nsiti vit y  
I n t he e ve nt of a se vere l ocal a n d/ or s yste mic h y p erse nsiti vit y reacti o n p ossi bl y or pr o b a bl y relate d 
t o trial pr o d uct, bl o o d sa m pli n g f or ass ess me nt of t he f oll o wi n g s h o ul d be c o n d ucte d wit hi n 3 h o urs 
of t he reacti o n, 1 -2 wee ks after t he reacti o n, 3 -4 wee ks aft er t he reacti o n a n d if p ossi bl e, 3 m o nt hs 
after t he reacti o n. A nal ysis will be perf or me d b y N o v o N or dis k.  
•  a nti-N N C 0 1 6 5 -1 8 7 5 I g E a nti b o dies  
•  a nti-N N C 0 1 6 5 -1 8 7 5 bi n di n g a nti b o dies (a d diti o nal t o sc he d ule d ti me p oi nts)  
I n a d diti o n t o a b o ve, bl o o d sa m pli n g f or assess m e nt of tr y ptase (t otal a n d/ or mat ure tr y ptas e) 
s h o ul d be c o n d ucte d wit hi n 3 h o urs of t he reacti o n a n d 1-2 wee ks aft er t he reacti o n (t o b e use d as 
baseli ne c o nce ntrati o n) . 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
 .
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1
 |
 of
  Pr ot oc ol  versi o n 4. 0
6 8
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
6 9  of 1 1 6  
 
9  St atistic al c o nsi der ati o ns   
9. 1  
St atistic al h y p ot heses  
P art 1  
T here is n o f or mal h y p ot hesis testi n g f or Part 1.  
P art 2  
F or t he pri mar y e n d p oi nt perce nt a ge wei g ht c ha n ge fr o m ra n d o misati o n ( wee k 3 2 ) t o 
e n d-of -tr eat me nt ( wee k 48 ), t he s u peri orit y test f or N N C 0 1 6 5-1 8 7 5 1. 0 m g a n d se ma gl uti de s.c. 2. 4 
m g vers us pl ace b o 1. 0 m g a n d s e ma gl uti de s.c. 2. 4 m g will be carrie d o ut as f oll o ws. As all s u bjects 
will recei ve s e ma gl uti de s.c. 2. 4 m g a n d t o ease n otati o n, se ma gl uti de s.c. 2. 4 m g is i g n ore d i n t he 
n otati o n. Let μ N N C 0 1 6 5 -1 8 7 5 , 1 . 0 m g a n d μ place b o , 1. 0 m g de n ote t he tr ue mea n of perce nta ge wei g ht c ha n ge 
f or d ose le vel N NC 0 1 6 5 -1 8 7 5 1 . 0 m g a n d t he pl ace b o 1. 0 m g gr o u p, res p ecti vel y.  
T he n ull a n d alter nati ve h y p ot hes es teste d are  
𝐻0 : 𝜇N N C 0 1 6 5 −1 8 7 5  ,𝑥≥𝜇𝑝𝑙𝑎𝑐𝑒𝑏𝑜 vs.  𝐻𝐴:𝜇N N C 0 1 6 5 −1 8 7 5  ,𝑥< 𝜇𝑝𝑙𝑎𝑐𝑒𝑏𝑜 
T he n ull h y p ot hesis will be reje cte d if t he u p per li mit of t he esti mate d t w o -si de d 9 5 % CI f or t he 
treat me nt differe nce is bel o w 0.  
9. 2  
S a m ple size deter mi n ati o n  
P art 1  
Part 1 is e x pl orat or y i n n at ure, as t he pri mar y o bjecti ve is t o assess safet y a n d t olera bil it y f oll o wi n g 
m ulti ple s.c. o nce -wee kl y d oses of N N C 0 1 6 5 -1 8 7 5 a n d se ma gl uti de. T heref ore, t h e sa m ple siz e is 
n ot base d o n a f or mal statistical assess me nt b ut  is c o nsi dere d  t o be s ufficie nt t o e val uate t he safet y 
a n d t olera bilit y b ase d o n s u m maries of res ul ts. S pecificall y, i n Part 1 , 2 4 s u bjects will be 
ra n d o mise d 2: 1: 2: 1 t o recei ve N N C 0 1 6 5-1 8 7 5 1. 0 m g, N N C 0 1 6 5 -1 8 7 5 1. 0 m g place b o, N N C 0 1 6 5 -
1 8 7 5 2. 0 m g or N N C 0 1 6 5 -1 8 7 5 2. 0 m g place b o. All s u bjects will recei ve se ma gl uti de.  
A p pr o xi matel y 7 5  s u bj ects will be scree ne d t o ac hie ve 2 4 s u bjects ra n d o ml y assi g ne d t o trial 
pr o d uct.  
P art 2  
T a x o n o m y of w ee k 4 8  assess me nts  
F or eac h s u bject , a gi ve n assess me nt at wee k 4 8  ma y b e a v aila ble or missi n g a n d t h e s u bject ma y be 
o n ra n d o mise d treat me nt or n ot. Ta ble  9 -1  des cri b es t he ta x o n o m y f or t his. N ote t hat t his is d o ne 
per assess me nt a n d per s u bject; s u bjects ma y be a differe nt t y pe f or differe nt assess m e nts (a s u bject 
ma y h a ve ‘a vaila ble o n ra n d o mise d treat me nt (A T )’ f or b o d y wei g ht b ut ‘ missi n g o n ra n d o mise d 
treat me nt (M T )’ f or waist circ u mfere nce). 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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-
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1
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 of
  Pr ot oc ol  versi o n 4. 0
6 9
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
7 0  of 1 1 6  
 
T a ble  9 -1  
T a x o n o m y f or s u bjects b ase d o n wee k 4 8  assess me nts  
Assess me nt  
at w ee k 4 8  
S u bjects o n 
r a n d o mise d 
tre at me nt at 
w ee k 4 8  
T y pe descri pti o n  
T y pe  
A b bre vi ati o n  
A vaila ble  
Yes  
A vaila ble o n ra n d o mise d treat me nt:  
S u bj ects w h o c o m plete t he tri al o n ra n d o mise d treat me nt wit h 
a n assess me nt at wee k 4 8 . T his i ncl u des t h ose t hat st o p a n d 
restart trial pr o d uct. 
A T  
N o  
A vaila ble b ut disc o nti n ue d  
S u bj ects w h o disc o nti n ue ra n d o mise d treat me nt pre mat urel y 
b ut ret ur n t o ha ve a n assess me nt at wee k 4 8 . T hese are als o 
calle d retrie ve d s u bj ects.  
A D  
Missi n g  
Yes  
Missi n g  o n ra n d o mise d treat me nt:  
S u bj ects w h o c o m plete t he tri al o n ra n d o mise d treat me nt 
wit h o ut a n assess me nt at wee k 4 8 . T his i ncl u des t h ose t hat 
st o p a n d restart trial pr o d uct. 
M T  
N o  
Missi n g a n d disc o nti n ue d:  
S u bj ects w h o disc o nti n ue ra n d o mise d treat me nt pre mat urel y 
a n d d o n ot ret ur n t o ha ve a n assess me nt at wee k 4 8 . T hese are 
als o calle d n o n -retrie ve d s u bj ects. 
M D  
S a m ple size ass u m pti o ns  
T he ass u m pti o ns f or t he sa m ple siz e calc ulati o ns are:  
•  T he t w o -si de d si g nifica n ce le vel is 5 % 
•  5 0 s u bjects are ra n d o mise d t o t he N N C 0 1 6 5 -1 8 7 5 a d de d o n t o se ma gl uti de ar ms  
•  2 5 s u bjects are ra n d o mise d t o t he N N C 0 1 6 5 -1 8 7 5 place b o a d d e d o n t o se m a gl uti de ar ms  
Ass u m pti o ns c orres p o n di n g t o t he pri mar y esti ma n d:  
•  N o n -retrie v e d s u bjects ( M D) i n a n y of t he acti ve ar ms are ass u me d t o ha ve a 1 1 % b o d y wei g ht 
gai n c o m pare d t o s u bje ct c o m pleti n g treat me nt wit h place b o a d d e d o n t o se ma gl uti de s.c. 
2. 4  m g  
•  Retrie ve d s u bjects ( A D) i n a n y of t h e acti ve ar ms are ass u me d t o h a ve a n effect c orres p o n di n g 
t o half t he treat ment differe nce b et wee n n o n -retrie ve d s u bjects a n d s u bjects w h o c o m plete t he 
trial i n t hat ar m ( A T) 
•  T he gr o u ps of n o n -retrie ve d s u bjects, retri e ve d s u bjects a n d c o m pleters are ass u me d t o ha ve a 
sta n dar d de viati o n f or b o d y w ei g ht c ha n ge of 4. 8 % 
•  1 0 % of s u bject s are ass u me d t o disc o nti n ue ra n d o mise d treat me nt per ma ne ntl y a n d 6 0 % of 
t hese are retri e ve d ( A D) at wee k 48  ( Base d o n dat a fr o m trial N N 9 5 3 6-4 1 5 3)  
•  Sta n dar d de viati o n aft er a dj ust me nt f or treat me nt disc o nti n uati o n a n d missi n g dat a is 5. 9 %  
•  T he treat me nt differe nces are a n al ys e d b y t w o -si d e d t-tests w hic h is a si m plificati o n of t he mai n 
a nal ys es i ncl u di n g e x pla nat or y v aria bl es.  
Gi ve n t he ass u m pti o ns a b o ve, a treat me nt differe nce of N N C 0 1 6 5 -1 8 7 5 a d de d o n t o se ma gl uti de 
s.c. 2. 4 m g c o m pare d t o place b o a d d e d o n t o se m a gl uti de s.c. 2. 4 m g f or c o m pleters of 4. 5 % 
c orres p o n ds t o a treat me nt differe n ce of 4. 2 % f or tar geti n g t h e treat me nt p olic y esti ma n d. Sta n dar d 
de viati o n after a dj ust me nt f or treat me nt disc o nti n u ati o n a n d missi n g d ata is 5. 9 %. 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
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1
 |
 of
  Pr ot oc ol  versi o n 4. 0
7 0
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
7 1  of 1 1 6  
 
F urt her m ore, 5 0 s u bjects ra n d o mise d t o N N C 0 1 6 5 -1 8 7 5 1 . 0 m g a d de d o n t o se ma gl uti de ar m a n d 
2 5 ra n d o mise d t o t he N N C 0 1 6 5 -1 8 7 5 place b o a d d e d o n t o se ma gl uti de ar ms, gi ves a p o wer of 8 1 % 
f or t he test of differe n ce bet wee n hi g h d ose of N N C 0 1 6 5-1 8 7 5 c o m bi ne d wit h se ma gl uti de a n d 
place b o gr o u p u n d er t he ass u m pti o n of a 4. 5 % -p oi nt differe nce i n wei g ht l oss f or c o m pleters.  
Base d o n N N 9 5 3 6 -4 3 7 6 , it is e x pecte d t hat 1 1 % s u bjects will dr o p o ut b y wee k 3 2 . T o acc o u nt f or 
t his, it is pla n ne d t o e nr ol 9 0 s u bjects. F urt her, a p pr o xi matel y 1 0 6 s u bjects will be scree n e d t o 
e ns ure 9 0 s u bjects f or e nr ol me nt.  
T he pr o ba bilities a n d p o wer calc ulati o ns be neat h are bas e d o n ass u m pti o ns f or t he pri mar y 
esti ma n d. H o we ver, b ot h t he pri mar y a n d sec o n dar y esti ma n ds will be c o vere d, si nce t he 
pr o ba bilities a n d p o wer f or t he sec o n d ar y esti ma n d are hi g her c o m pare d t o t he pri mar y esti ma n d.  
I n pr ot oc ol versi o n 4. 0, t he a d diti o nal r u n-i n visits ( V 9. 1 a n d V 9. 2) h a ve b ee n acti vate d, t his mea ns 
t hat t he s u bjects will be 8 wee ks l o n ger o n s e ma gl uti de 2. 4 m g bef ore ra n d o misati o n. H o we ver, t his 
d oes n ot affect t he p o wer.  
Ta ble  9 -2  lists t he p o wer f or differe nt c h oices of s a m ple siz e a n d ass u me d treat me nt differe n ce f or 
c o m pleters.  
T a ble  9 -2  
P o w er w he n c o m p ari n g N N C 0 1 6 5 -1 8 7 5 1. 0 m g a d de d o n t o se m a gl uti de s.c. 2. 4 
m g v ers us pl ace b o a d d e d o n t o se m a gl uti de s.c. 2. 4 m g  
N s u bjects r a n d o mise d 2: 1  
Tre at me nt differe nce  
P o w er  
6 0  
4. 0  
6 3 %  
7 5  
4. 0  
7 3 %  
9 0  
4. 0  
8 0 %  
6 0  
4. 5  
7 2 %  
7 5  
4. 5  
8 1 %  
9 0  
4. 5  
8 8 %  
6 0  
5. 0  
8 0 %  
7 5  
5. 0  
8 8 %  
9 0  
5. 0  
9 3 %  
 
9. 3  
P o p ul ati o ns f or a n al yses  
T he f oll o wi n g p o p ul ati o n s are defi ne d : 
P o p ul ati o n  
Descri pti o n  
F ull a nal ysis set  
F ull a nal ysis set ( F A S): All s u bj ects ra n d o mise d. E xcl usi o n of data fr o m a nal yses 
s h o ul d be use d restricti vel y, a n d n or mall y n o data s h o ul d be e xcl u de d fr o m t he F A S. 
S u bj ects will be a nal yse d acc or di n g t o  t he ra n d o mise d treat me nt 
Safet y  a nal ysis set  
Safet y a nal ysis set ( S A S): All s u bj ects ra n d o ml y assi g ne d t o trial treat me nt a n d w h o 
ta ke at least o ne d ose of trial pr o d uct. S u bj ects are a nal yse d acc or di n g t o t he treat me nt 
t he y act uall y recei ve d. 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
7 1
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
7 2  of 1 1 6  
 
T he s u bj ects or o bser vati o ns t o be e x cl u de d, a n d t he reas o ns f or t heir e x cl usi o n m ust be 
d oc u me nte d bef ore u n bli n di n g. T he s u bjects a n d o bser vati o ns e x cl u de d fr o m a nal ysis sets, a n d t h e 
reas o n f or t his, will be d oc u me nte d i n t he C T R. 
Tre at me nt peri o ds  
T hree o bser v ati o n peri o ds are defi ne d f or eac h s u bject i n Part 2:  
•  I n-trial: T he i n-trial peri o d is defi ne d as t he u ni nterr u pte d ti me i nter val fr o m date of 
ra n d o misati o n t o date of last c o ntact wit h trial site. 
•  O n -treat me nt: A ti me-p oi nt is c o nsi dere d as ‘ o n -tr eat me nt’ if a n y d os e of trial pr o d ucts has bee n 
a d mi nistere d wit hi n t he pri or 8 wee ks. T h e o n -tr eat me nt peri o d is defi ne d as all ti mes w hic h are 
c o nsi dere d o n -treat me nt. T he o n-treat me nt peri o d will t heref ore b e fr o m t h e date of first trial 
pr o d uct a d mi nistrati o n t o date of last trial pr o d u ct a d mi nistrati o n e x cl u di n g p ote ntial 
off -treat me nt ti me i nter vals. 
•  Treat me nt -a d here nt: A ti me -p oi nt is c o nsi dere d as ‘treat me nt -a d here nt’ if trial pr o d uct has bee n 
a d mi nistere d wit hi n t he pri or 2 wee ks wit h N N C 0 1 6 5 -1 8 7 5 a n d se ma gl uti d e a n d o nl y bef ore t he 
first e ve nt of ‘tr eat me nt n o n-a d here nce’. T he d eri v e d date of t he misse d or l o were d d os e 
ca usi n g treat me nt n o n -a d here nce (sec o n d c o ns ec uti ve wit h N N C 0 1 6 5 -1 8 7 5 or se ma gl uti de) will 
be use d as t he lat est date f or i ncl u di n g assess m e nts i n t his o bser vati o n peri o d. F or s u bjects w h o 
i nitiate a n y ot her wei g ht l oss i nter ve nti o n bef ore t his date, t he date of starti n g ot her wei g ht 
ma na ge me nt dr u gs or u n der g oi n g bariatri c s ur ger y will be use d as latest date f or usi n g 
assess me nts i n t his o bs er vati o n peri o d. T h us, t he assess me nt cl osest i n ti me a n d bef ore t he dat e 
of starti n g a n y wei g ht l oss i nter ve nti o n will be use d as last assess me nt o n ra n d o mise d treat me nt. 
F or s u bjects n ot reac hi n g tar get d ose acc or di n g t o t he escalati o n r e gi me n n o p ost -ba seli ne 
assess me nts will be i ncl u de d.  
T he i n -trial a n d o n-tr eat me nt peri o ds defi ne t he patie nt years of o bs er vati o n ( P Y O) a n d patie nt 
years of e x p os ure ( P Y E), res pecti vel y, as t he t otal ti me d urati o n i n t he peri o ds. 
9. 4  
St atistic al a n al yses  
T he statistical a nal ysis pla n ( S A P) will be fi nalise d pri or t o data base l o c k  ( D B L), a n d it will i ncl u de 
a m ore tec h ni cal a n d d etaile d descri pti o n of t he statistical a nal ys es descri b e d i n t his secti o n.  T his 
secti o n is a s u m mar y of t he pla n ne d statistical a nal yses of t h e m ost i m p orta nt e n d p oi nts i ncl u di n g 
pri mar y a n d c o nfir mat or y sec o n dar y e n d p oi nts.  
9. 4. 1  
Ge ner al c o nsi der ati o ns  
H a n dli n g of missi n g b aseli ne d at a  
T he last a vaila ble a n d eli gi ble o bser vati o n at or bef ore ra n d o misati o n is use d as t he baseli ne v al ue. 
If n o assess me nts are a v aila ble, t he mea n val ue at ra n d o misati o n acr oss all eli gi ble s u bjects is use d 
as t he baseli ne v al ue.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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1
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 of
  Pr ot oc ol  versi o n 4. 0
7 2
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
7 3  of 1 1 6  
 
9. 4. 2  
Pri m ar y e n d p oi nt  
Defi niti o n of pri mar y e n d p oi nt: % wei g ht c ha n ge  
C ha n ge fr o m r a n d o misati o n at wee k 3 2  t o w ee k 4 8  i n b o d y wei g ht ( %) is defi ne d as: 
% wei g ht c ha n ge =  ( b o d y wei g ht at wee k 4 8  –  b o d y wei g ht at w e e k 3 2 )
b o d y wei g ht at w e e k 3 2
 × 1 0 0 %  
A n al yses a d dressi n g t he pri m ar y esti m a n d  
T he f oll o wi n g statistical a nal ys es a n d i m p utati o n met h o ds are desi g ne d t o a d dress t he pri mar y 
esti ma n d, i.e. , t o assess t he effecti ve n ess of N N C 0 1 6 5 -1 8 7 5  1. 0 m g .  
T he a nal ysis m o del f or % wei g ht c ha n ge is a n A N C O V A wit h ra n d o mise d treat me nt as fact or a n d 
baseli ne b o d y wei g ht ( k g) as a c o v ariate.  
Pri m ar y i m p ut ati o n a p pr o ac h f or t he pri m a r y esti m a n d ( R S -MI)  
T he pri mar y a n al ysis  of t he pri mar y esti ma n d is a retrie ve d s u bjects -bas e d m ulti ple i m p utati o n 
a p pr oac h ( R S -MI) w hic h is si m plifie d b ut si milar t o t he o ne descri b e d b y Mc E v o y
4 3. Missi n g b o d y 
wei g ht meas ure m e nt at wee k 4 8  f or n o n-retrie ve d s u bjects ( M D) are i m p ute d usi n g ass ess me nts 
fr o m retrie v e d s u bjects ( A D). Missi n g b o d y wei g ht meas ure me nts at w ee k 4 8  f or s u bjects o n 
ra n d o mise d treat me nt ( M T) are i m p ute d usi n g a v aila ble meas ure me nts at w ee k 48  fr o m s u bjects o n 
ra n d o mise d treat me nt ( A T). 
T he m ulti ple i m p utati o n a p pr oac h is d o n e i n t hree ste ps:  
1.  I m p ut ati o n: A n i m p utati o n m o del is defi ne d usi n g retrie ve d s u bjects ( A D) fr o m t he F A S. T h e 
m o del will be a li near re gressi o n of b o d y wei g ht ( k g) at wee k 4 8  wit h treat me nt as fact or a n d 
baseli ne b o d y wei g ht ( k g), last a vaila ble treat me nt -a d here nt o bser vati o n of b o d y wei g ht ( k g) 
a n d n u m ber of da ys i n t he treat me nt -a d here nt o bs er vati o n peri o d a s c o variates. N o i nteracti o ns 
will be i ncl u de d. If a n y s u bjects are M T, a n i m p utati o n m o del f or missi n g b o d y wei g ht 
meas ure me nts at w ee k 4 8  f or M T s u bjects will als o be defi ne d usi n g A T s u bjects i n a si milar 
wa y. T he esti mate d p osteri or distri b uti o n f or t h e para meters (re gressi o n c o efficie nts a n d 
varia nces) i n t he i m p utati o n m o dels are t he n use d t o i m p ute missi n g wee k 4 8  b o d y wei g ht 
val ues. T his will be d o ne 1 0 0 0 ti mes, res ulti n g i n 1 0 0 0 c o m plete data sets.  
2.  A n al ysis : A nal ysis of eac h of t he 1 0 0 0 c o m plete data sets usi n g t he A N C O V A wit h treat me nt 
as fact or a n d bas eli ne b o d y w ei g ht as c o variate, res ulti n g i n 1 0 0 0 esti mates f or eac h treat me nt 
c o m paris o n.  
3.  P o oli n g : T he 1 0 0 0 esti mati o n res ults are i nte grate d i nt o a fi nal res ult usi n g R u bi n’s f or m ula. 
T he esti mate d treat me nt differe n ce b et wee n N N C 0 1 6 5 -1 8 7 5 1. 0 m g  d ose as a d d o n t o se ma gl uti de 
s.c. 2. 4  m g a n d place b o gr o u p will be re p orte d t o get her wit h t he ass oci ate d t w o -si de d 9 5 % CI a n d 
c orres p o n di n g t w o -si d e d p-val ue.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
 .
-
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1
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 of
  Pr ot oc ol  versi o n 4. 0
7 3
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
7 4  of 1 1 6  
 
Se nsiti vit y a n al yses  
T he se nsiti v it y a nal ys es i n vesti gate h o w ass u m pti o ns o n b o d y wei g ht d e vel o p me nt after 
disc o nti n uati o n of ra n d o mise d treat me nt i m pact t he esti mate d treat me nt c o ntrasts bet wee n acti ve 
d oses a n d place b o. T his will be d o ne usi n g a m ulti ple i m p utati o n a p pr oac h usi n g retrie ve d s u bjects. 
T he details of t he se nsiti vit y a nal yses will be gi v e n i n t he S A P.  
Ti p pi n g -p oi nt m ulti ple i m p utati o n a nal ysis ( T P -MI): First, missi n g dat a are i m p ute d acc or di n g t o 
t he pri mar y R S-MI a nal ysis. Sec o n d, f or t he acti ve treat me nt ar m , a pe n alt y wil l be a d d e d t o t he 
i m p ute d val ues at wee k 4 8 . T he a p pr oac h is t o gra d uall y i ncreas e t his pe nalt y u ntil all c o ncl usi o ns 
fr o m t he pri mar y a nal ysis are re vers e d. F or s u peri orit y h y p ot hesis testi n g a n N N C 0 1 6 5-1 8 7 5 d ose 
pl us se ma gl uti de vs. place b o t he s pecifi c val ue of t he pe nalt y t hat re v erses t he c o ncl usi o n will be 
use d t o e val uate t he r o b ust ness of t he ass u m pti o n t hat s u bjects wit h missi n g dat a ha ve t h e sa me 
effect as place b o.  
9. 4. 3  
Sec o n d ar y e n d p oi nt  
9. 4. 3. 1  
C o nfir m at or y s ec o n d ar y e n d p oi nts  
N ot a p plica ble f or t his trial.  
9. 4. 3. 2  
S u p p orti ve sec o n d ar y e n d p oi nts  
S u p p orti ve sec o n dar y e n d p oi nts are liste d i n Secti o n 3 . 
Effic ac y e n d p oi nts  
C ha n ge fr o m r a n d o misati o n at wee k 3 2  t o w ee k 4 8  i n: 
•  B o d y wei g ht ( k g)  
•  Waist circ u mfere n ce (c m)  
•  H b A 1 c ( %-p oi nt)  
•  Fasti n g Plas ma Gl uc ose ( m m ol/l)  
•  Fasti n g i ns uli n ( p m ol/l)  
T hese c o nti n u o us s u p p orti ve sec o n dar y effi cac y e n d p oi nts will be a nal yse d usi n g t he sa me a nal ysis 
m o del as t he pri mar y a n al ysis f or t he pri mar y e n d p oi nt a d dressi n g t he pri mar y esti ma n d descri be d 
i n Secti o n 9. 4. 2 . T he o utc o me varia bl e % wei g ht c ha n ge a n d t he c o v ariate baseli ne b o d y wei g ht 
will be re place d b y t he c orres p o n di n g o utc o me a n d baseli ne assess me nts of t he e n d p oi nt t o be 
a nal ys e d. T he esti mate d treat me nt differe n ce bet w ee n i n di vi d ual N N C 0 1 6 5-1 8 7 5 1. 0 m g d oses as 
a d d o n t o se ma gl uti de  s.c. 2. 4 m g a n d place b o gr o u p will be re p orte d t o get her wit h t he ass ociat e d 
t w o-si de d 9 5 % CI. 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
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1
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 of
  Pr ot oc ol  versi o n 4. 0
7 4
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
7 5  of 1 1 6  
 
Relati ve c ha n ge fr o m r a n d o misati o n at wee k 3 2  t o wee k 4 8  i n f oll o wi n g li pi ds: 
•  T otal c h olester ol  
•  H D L c h olester ol  
•  L D L c h olester ol  
•  V L D L c h olester ol  
•  Tri gl yceri des  
•  Free Fatt y aci ds  
F or li pi ds , a m ulti plicati ve m o del will be use d, i.e. , t he rati o bet wee n p ost-ra n d o misati o n 
meas ure me nts a n d b aseli ne will be a nal yse d as t he o utc o me vari a ble i nstea d of differe nces, a n d 
b ot h t he o utc o me varia bl e a n d t he bas eli ne assess me nt will be l o g -tr a nsf or me d pri or t o a nal ysis. 
T hese e n d p oi nts will be s u m marise d b y d escri pti v e statistics usi n g t he F A S.  
T he a nal ysis m o del f or % wei g ht  c ha n ge will be a nal ys e d usi n g M M R M wit h t he  sa me fact or a n d 
c o variate as f or t h e pri mar y a nal ysis all neste d wit hi n visit. I n t h e a nal ysis all t he data fr o m t he 
s u bjects w h o re mai n o n t heir ra n d o mise d tr eat me nt f or t he e ntire pla n ne d d urati o n of t he treat me nt 
peri o d or u ntil bef ore t he start of resc u e i nter ve nti o n (a nti -o besit y dr u gs or bariatric s ur ger y) or u ntil 
first disc o nti n ui n g of ra n d o mise d treat me nt. T he esti mate d treat me nt differe nce b et wee n i n di vi d ual 
N N C 0 1 6 5 -1 8 7 5  1. 0 m g  d oses as a d d o n t o se ma gl uti de  s.c. 2. 4 m g a n d pl ace b o gr o u p will be 
re p orte d t o get h er wit h t he ass ociate d t w o-si de d 9 5 % CI a n d c orres p o n di n g t w o-si de d p-val ue.  
S afet y E n d p oi nts  
P art 1  
A T E A E is defi ne d as a n e ve nt t hat eit her:  
•  Has o nset after a d mi nistrati o n of trial pr o d uct a n d n o later t ha n t he f oll o w -u p visit  
•  Is prese nt bef ore trial pr o d uct a d mi nistrati o n a n d i ncreas es i n after t he first d ose of trial pr o d uct 
a n d n o later t ha n t he f oll o w -u p visit.  
•  N o f or mal statistical i nfere nce will be carrie d o ut base d o n t he n u m ber of T E A Es a n d S A Es. 
T E A Es a n d treat me nt -e m er ge nt S A Es will be s u m marise d b y descri pti ve statistics.  
P art 2  
A d verse e ve nts will be d efi ne d as ‘treat me nt-e mer ge nt ’ ( T E A E), if t he o ns et of t he e ve nt o cc urs i n 
t he o n-treat me nt p eri o d, see defi niti o n i n Secti o n 9. 2 . N o f or mal statistical i nfere n ce will be carrie d 
o ut base d o n t he n u m ber of T E A Es a n d S A Es. T E A Es a n d treat me nt e mer ge nt S A Es will be 
s u m marise d b y d escri pti ve statistics f or b ot h 1. 0 m g N N C 0 1 6 5 -1 8 7 5/ place b o a n d 2. 0 m g 
N N C 0 1 6 5 -1 8 7 5/ place b o . 
9. 4. 4  
E x pl or at or y e n d p oi nt  
N ot a p plica ble i n t his trial.  
9. 4. 5  
Ot her s af et y a n al yses  
All safet y a nal yses will be ma de o n t he safet y a n al ysis set. T he sta n d ar d safet y assess me nts ( A Es, 
safet y la b orat or y para met ers, vital si g ns, et c.) will be re p ort e d descri pti vel y. 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
7 5
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
7 6  of 1 1 6  
 
9. 4. 6  
Ot her a n al yses  
9. 4. 6. 1  
P h ar m a c o ki netic  a n d/ or p h ar m a c o d y n a mic m o delli n g  
P o p ulati o n P K a n d e x p os ure -res p o nse a n al ys es will be use d as s u p p orti ve e vi de nce f or t he 
e val uati o n of efficac y a n d safet y as w ell as t o s u p p ort t he d ose selecti o n of s .c. N N C 0 1 6 5 -1 8 7 5 f or 
f ut ure cli nical de v el o p me nt i n s u bjects wit h o besit y. Firstl y, plas ma N N C 0 1 6 5-1 8 7 5 c o nce ntrati o ns 
will be a nal ys e d usi n g a p o p ulati o n P K m o del, q ua ntif yi n g c o v ariat e (s uc h as baseli ne b o d y wei g ht, 
a ge, se x, race, et h nicit y) effects o n N N C 0 1 6 5 -1 8 7 5 e x p os ure. Sec o n dl y, m o del -base d esti mates of 
stea d y-state a v era ge c o n ce ntrati o ns will be deri ve d f or eac h s u bject, t o facilitate s u bse q ue nt 
e x p os ure-res p o nse a nal yses. Rele va nt efficac y a n d safet y e n d p oi nts will be related t o stea d y -state 
a vera ge c o n ce ntr ati o ns a n d s u bjecte d t o m o del -base d a nal ysis.  
A m o delli n g a n al ysis pla n will be pre pare d bef ore last patie nt last treat me nt, o utli ni n g details of t he 
a nal ys es. T he m o delli n g will be perf or me d b y Q ua ntitati ve Cli nical P har m ac ol o g y at N o v o N or dis k 
a n d will be re p ort e d se paratel y fr o m t he C T R.  
9. 5  
D at a b ase l oc k  
P art 1:  
D B L 1 of p art 1 will be p erf or me d after L P L V  ( wee k 1 6). T h e data i n sc o p e are p h ar mac o ki netic 
a n d safet y la b d ata u n til wee k 1 6, w hic h will be use d f or t he i nitial safet y c o m mittee decisi o n. After 
D B L 1 , dat a will be u n bli n de d f or part 1. U n bli n di n g after D B L 1 is n ot of a n y c o ncer n f or 
c o nti n ui n g part 2, as sites a n d s u bjects are dissi milar f or part 1 a n d p art 2 of t he trial.  
D B L 2 of p art 1 will be p erf or me d after t he rest of t he data has bee n c ollecte d. T he data i n s c o pe are 
p har mac o ki netic a n d safet y la b dat a (u n til wee k 2 4) a n d a nti b o d y dat a. 
P art 2:  
D B L of part 2 will be perf or me d aft er L P L V . After t he D B L has bee n c o m plete d, t he data will be 
u n bli n de d f or part 2.  
9. 6  
I nteri m a n al yses 
N ot a p plica ble i n t his trial.  
9. 7  
D at a m o nit ori n g c o m mittee  
N ot a p plica ble i n t his trial . 
9. 8  
Re p orti n g of t he m ai n p art of t he tri al  
N ot a p plica ble i n t his trial.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
 .
-
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1
 |
 of
  Pr ot oc ol  versi o n 4. 0
7 6
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
7 7  of 1 1 6  
 
1 0  S u p p ort i n g d oc u me nt ati o n a n d o p er ati o n al c o nsi de r ati o ns 
1 0. 1  A p pe n di x 1: Re g ul at or y, et hic al, a n d tri al o versi g ht c o nsi der ati o ns  
1 0. 1. 1  
Re g ul at or y a n d et hic al c o nsi der ati o ns  
T his trial will be c o n d ucte d i n acc or da nce wit h t he pr ot oc ol a n d wit h t he f oll o wi n g:  
•  C o nse ns us et hica l pri nci ples deri ve d fr o m i nter nati o nal g ui deli nes i ncl u di n g t he Declarati o n of 
Helsi n ki 4 4 a n d a p plica ble I C H G o o d Cli nical Practice ( G C P) G ui deli ne 4 5 
•  A p plica ble la ws a n d re g ulati o ns  
•  T he pr ot oc ol, i nf or me d c o nse nt f or m, In vesti gat or’s Br oc h ure (as a p plica ble) a n d ot her rele va nt 
d oc u me nts (e. g. , a d v ertis e me nts) m ust be s u b mitte d t o a n I R B/I E C a n d re vie we d a n d a p pr o ve d 
b y t he I R B/I E C bef ore t h e trial is i nitiate d.  
•  Re g ulat or y a ut h orities will recei ve t he cli nical trial a p plicati o n, pr ot oc ol a m e n d me nts, re p orts 
o n S A Es, a n d  t he C T R acc or di n g t o nati o nal re q uire me nts. 
•  A n y a me n d me nts t o t he pr ot oc ol will re q uire I R B/I E C a p pr o val bef ore i m ple me ntati o n of 
c ha n ges ma d e t o t he trial desi g n, e x ce pt f or c ha n ges necess ar y t o eli mi nate a n i m me diate safet y 
hazar d t o trial s u bjects.  
•  Bef ore a site is all o w e d t o start scree ni n g s u bjects, writte n n otificati o n fr o m N o v o N or dis k m ust 
be recei ve d.  
•  T he i n vesti gat or will be res p o nsi ble f or:  
•  P r o vi di n g writte n s u m maries of t he stat us of t he tri al a n n uall y or m ore fre q u e ntl y i n acc or da nce 
wit h t he re q uire me nts, p olicies, a n d pr oce d ures esta blis he d b y t he I R B/I E C a n d/ or re g ulat or y 
a ut h orities 
•  N otif yi n g t he I R B/I E C of S A Es or ot her si g nifica nt safet y fi n di n gs as re q uire d b y I R B/I E C 
pr oce d ures  
•  P r o vi di n g o versi g ht of t h e c o n d uct of t he trial at t he site a n d a d here n ce t o r e q uire me nts of I C H 
g ui deli nes, t he I R B/I E C, a n d all ot her a p plica ble l ocal re g ulati o ns  
•  E ns uri n g s u b missi o n of t he C T R s y n o psis t o t he I R B/I E C  
•  R e p orti n g a n y p ot e ntial seri o us breac hes t o t he s p o ns or i m me diatel y after disc o ver y  
1 0. 1. 2  
Fi n a nci al discl os ure  
I n v esti gat ors a n d s u b-i n v esti gat ors will pr o vi de N o v o N or dis k wit h s uffici e nt, acc urate fi na ncial 
i nf or mati o n as re q u este d t o all o w N o v o N or dis k t o s u b mit c o m plete a n d acc urate fi na ncial 
certificati o n or discl os ure state me nts t o t he a p pr o priate re g ul at or y a ut h orities. I n v esti gat ors are 
res p o nsi ble f or pr o vi di n g i nf or mati o n o n fi na ncial i nterests d uri n g t h e c o urse of t he trial a n d o ne 
year after c o m pleti o n of t he trial.  
Verific ati o n u n der discl os ures per C o de of Fe deral Re g ulati o ns ( C F R) of Fi na nc ial C o nflict of 
I nterest. 
1 0. 1. 3  
I nf or me d c o nse nt pr ocess 
•  T he i n vesti gat or or his/ her re prese nt ati ve will e x plai n t he nat ure of t h e trial t o t he s u bject a n d 
a ns wer all q uesti o ns re gar di n g t he tri al.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
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1
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 of
  Pr ot oc ol  versi o n 4. 0
7 7
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
7 8  of 1 1 6  
 
•  T he i n vesti gat or m ust e ns ure t he s u bject a m ple ti me t o c o me t o a  decisi o n w het her or n ot t o 
partici pate i n t he trial, if a p plica ble.  
•  S u bjects m ust be i nf or me d t hat t heir partici pati o n is v ol u ntar y.  
•  S u bjects m ust be i nf or me d a b o ut t heir pri vac y ri g hts.  
•  S u bjects will be re q uire d t o si g n a n d date a state m e nt of i nf or me d c o ns e nt t hat meets t he 
re q uire me nts of l o cal re g ulati o ns, I C H g ui deli nes4 5, Declarati o n of Helsi n ki4 4 a n d t he I R B/I E C 
or site.  
•  T he me dical r ec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o ns e nt was o btai ne d bef ore 
a n y tri al -rel ate d acti vit y a n d t he date w h e n t he writte n c o nse nt was o btai ne d. T he a ut h orise d 
pers o n o btai ni n g t h e i nf or me d c o nse nt m ust als o si g n a n d d ate t he i nf or m e d c o nse nt f or m bef ore 
a n y tri al relate d acti vit y.  
•  T he res p o nsi bilit y of s ee ki n g i nf or me d c o nse nt m ust re mai n wit h t he i n vesti gat or, b ut t he 
i n vesti gat or ma y d ele gat e t he tas k t o a me dicall y q ualifie d pers o n, i n acc or da nce wit h l ocal 
re q uire me nts. 
•  S u bjects m ust be re -c o ns e nte d t o t he m ost c urre nt versi o n of t he i nf or me d c o nse nt f or m (s) 
d uri n g t heir p artici pati o n i n t he trial.  
1 0. 1. 4  
I nf or m ati o n t o s u bjects d uri n g tri al 
T he site will be offere d a c o m m u nicati o n pac ka ge f or t he s u bject d uri n g t h e c o n d uct of t he trial. 
T he pac k a ge c o nt e nt is iss ue d b y N o v o N or dis k. T he c o m m u nicati o n pac k a ge will c o ntai n writte n 
i nf or mati o n i nte n de d f or distri b uti o n t o t he s u bjects. T he writte n i nf or mati o n will be tra nslate d a n d 
a dj uste d t o l ocal re q uir e me nts a n d distri b ute d t o t he s u bject at t he discreti o n of t he i n vesti gat or. T he 
s u bject ma y recei ve a “ w elc o me t o t he trial letter” a n d a “t ha n k y o u f or y o ur partici pati o n letter” 
after c o m pleti o n of t he trial. F urt her, t h e s u bject ma y recei ve ot her writte n i nf or mati o n d uri n g t he 
trial. 
All writte n i nf or mati o n t o s u bjects m ust be se nt t o I R B/I E C f or a p pr o val/fa v o ura ble o pi ni o n a n d t o 
re g ulat or y a ut h orities f or a p pr o val or n otificati o n accor di n g t o l ocal re g ulati o ns.  
1 0. 1. 5  
D at a pr otecti o n  
•  S u bjects will be assi g ne d a 6 -di git u ni q ue i de ntifier, a s u bject n u m ber. A n y s u bject rec or ds or 
datasets t hat are tra nsf erre d t o N o v o N or dis k will c o ntai n t he i de ntifier o nl y. N o direct 
i de ntifiers fr o m t he s u bject are tr a nsferre d t o N o v o N or dis k.  
•  T he s u bject a n d a n y bi ol o gic al material o btai ne d fr o m t he s u bject will be i de ntifie d b y s u bj ect 
n u m ber, visit n u m ber a n d trial I D. A p pr o pri ate m eas ures s u c h as e n cr y pti o n or lea vi n g o ut 
certai n i de ntifiers will be e nf or ce d t o pr otect t he i de ntit y of s u bjects as re q uire d b y l o cal, 
re gi o nal a n d nati o nal re q uire me nts. 
•  T he s u bject m ust be i nf or me d a b o ut his/ her pri vac y ri g hts, i ncl u di n g t hat his/ her pers o nal trial 
relate d dat a will be use d b y N o v o N or dis k i n acc or da nce wit h l ocal data pr otecti o n la w. T he 
discl os ure of t he dat a m ust als o be e x plai ne d t o t he s u bject.  
•  T he s u bject m ust be i nf or me d t hat his/ her me dical rec or ds ma y b e e x a mi ne d b y a u dit ors or 
ot her a ut h orise d pers o n n el a p p oi nte d b y N o v o N or dis k, b y a p pr o priate I R B/I E C me m bers, a n d 
b y i ns pect ors fr o m re g ulat or y a ut h orities.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
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 of
  Pr ot oc ol  versi o n 4. 0
7 8
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
7 9  of 1 1 6  
 
1 0. 1. 6  
C o m mittees st r uct ure  
1 0. 1. 6. 1  
N o v o N or dis k s af et y c o m mittee  
N o v o N or dis k will perf or m o n g oi n g safet y s ur veilla nce. If ne w s afet y si g nals are i de ntifie d, t hes e 
will be e val uate d b y a n i nter nal safet y c o m mittee. T he  safet y c o m mittee ma y rec o m me n d 
u n bli n di n g of a n y dat a f or f urt her a nal ysis, a n d i n t his case a n i nter nal trial i n de pe n de nt a d h oc 
gr o u p will be esta blis he d i n or der t o mai ntai n t he bli n di n g of t he trial pers o n nel.  
1 0. 1. 6. 2  
I nter n al N o v o N or dis k s afet y o versi g ht gr o u p  
F or Part 1 , N o v o N or dis k will c o nstit ute a n i nter nal N o v o N or dis k safet y o v ersi g ht gr o u p t o 
e val uate safet y a n d N N C 0 1 6 5 -1 8 7 5 P K data o n a n o n g oi n g basis. T he i nter nal N o v o N or dis k safet y 
o versi g ht gr o u p will w or k u n der pre -defi n e d c o n diti o n s acc or di n g t o ‘t he i nter nal N o v o N or dis k 
safet y o versi g ht gr o u p c h arter’. If a s afet y c o ncer n e mer ges, t he i nter nal N o v o N or dis k safet y 
o versi g ht gr o u p will i nf or m t he N o v o N or dis k safet y c o m mittee. T he N o v o  N or dis k safet y 
c o m mittee will deci de o n p ote nti al acti o ns t o be ta ke n.  
1 0. 1. 6. 3  
D at a m o nit ori n g c o m mittee  
N ot a p plica ble i n t his trial.  
1 0. 1. 6. 4  
E ve nt a dj u dic ati o n c o m mittee  
N ot a p plica ble i n t his trial.  
1 0. 1. 7  
Disse mi n ati o n of cli nic al tri al d at a  
I nf or mati o n of t he trial will be discl ose d at cli nicaltrials. g o v a n d n o v o n or dis k-trials.c o m. It will als o 
be discl ose d acc or di n g t o ot her a p plica ble re q uir e me nts, s uc h as t h ose of t he I nter n ati o nal 
C o m mittee of Me dical J o ur nal E dit ors (I C MJ E) 4 6, t he F o o d a n d Dr u g A d mi nistrati o n A me n d me nt 
Act ( F D A A A) 4 7, E ur o pea n C o m missi o n Re q uire me nts4 8 -5 0 a n d ot her rele va nt rec o m me n d ati o ns or 
re g ulati o ns. If a s u bject r e q uests t o be i ncl u de d i n t he trial via t he N o v o N or dis k e-mail c o ntact at 
t hese we b sites, N o v o N or dis k ma y discl ose t h e i n vesti gat or’s c o ntact details t o t he s u bject. As a 
res ult of i ncreasi n g re q uire me nts f or tr a ns pare nc y, s o me c o u ntries re q uir e p u blic discl osure of 
i n vesti gat or n a mes a n d t heir affiliati o ns. 
T he pri mar y c o m pleti o n date ( P C D) is t he last ass ess me nt of t he pri mar y e n d p oi nt a n d  is f or t his 
trial last s u bject first visit ( L S F V) i n Part 2 a + 48  wee ks c orres p o n di n g t o visit 1 8. If t he last s u bject 
is wit h dra w n earl y, t he P C D is c o nsi dere d t he dat e w he n t he last s u bject w o ul d ha ve c o m plete d visit 
1 8. T he P C D deter mi nes t he dea dli ne f or res ults discl os ure at cli nicaltrials. g o v acc or di n g t o 
F D A A A.  
1 0. 1. 8  
D at a q u alit y ass ur a nce  
1 0. 1. 8. 1  
C ase re p ort f or ms  
•  N o v o N or dis k or desi g nee is res p o nsi ble f or t he d ata ma na ge me nt of t his trial i ncl u di n g q ualit y 
c hec ki n g of t he d ata.  
•  All s u bject data rel ati n g t o t he trial will be rec or de d o n electr o nic C R Fs u nl ess tra ns mitte d 
electr o nicall y t o N o v o N or dis k or desi g n ee (e. g. , l a b orat or y a n d diar y d at a). T he i n vesti gat or is 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
7 9
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
8 0  of 1 1 6  
 
res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y p h ysi call y or electr o nicall y 
si g ni n g t he C R F. 
•  T he f oll o wi n g will be pr o vi de d as pa per C R Fs:  
•  Pre g n a nc y f or ms  
•  T he f oll o wi n g will be pr o vi de d as pa pe r C R Fs t o be use d w he n access t o t he eC R F is re v o k e d or 
t he e C R F is te m p oraril y u na vaila ble:  
•  A E f or ms   
•  Safet y i nf or mati o n f or ms  
•  Tec h nical c o m plai nt f or ms (als o t o be use d t o re p ort c o m plai nts o n trial pr o d uct n ot yet 
all ocate d t o a s u bject)  
•  C orrecti o ns t o  t he C R F d ata ma y be ma de b y t he i n vesti gat or or t he i n vesti gat or’s dele gate d 
staff. A n a u dit trail will b e mai ntai ne d i n t he C R F a p plicati o n c o ntai ni n g as a mi ni m u m: t he ol d 
a n d t he ne w d ata, i de ntifi cati o n of t he pers o n e nteri n g t he dat a, date a n d ti me o f t he e ntr y a n d 
reas o n f or t he c orrecti o n. If c orrecti o ns are ma de b y t he i n vesti gat or’s dele gat e d staff after t h e 
date w he n t he i n v esti gat or si g ne d t h e C R F, t he C R F m ust be si g n e d a n d dat e d a gai n b y t he 
i n vesti gat or. 
•  T he i n vesti gat or m ust e ns ure t hat data  is r ec or de d i n t he C R F as s o o n as p ossi ble, prefera bl y 
wit hi n 5 w or ki n g da ys after t he visit. O nce dat a has bee n e ntere d, it will be a vaila ble t o 
N o v o  N or dis k A/ S f or data verific ati o n a n d vali dati o n p ur p oses.  
1 0. 1. 8. 2  
M o nit ori n g  
•  T he i n vesti gat or m ust per mit trial -relate d m o nit ori n g, a u dits, I R B/I E C re vi e w, a n d re g ulat or y 
a ge nc y i ns pe cti o ns a n d pr o vi de direct access t o s o urce dat a d oc u me nts ( ori gi nal d oc u m e nts, 
data a n d rec or ds). Direct access i ncl u des per missi o n t o e xa mi ne, a nal yse, v erif y a n d re pr o d uce 
a n y rec or d (s) a n d re p ort(s) t hat are i m p orta nt t o t h e e val uati o n of t he trial. If t he electr o nic 
me dical rec or d d oes n ot ha ve a visi ble a u dit trail, t he i n vesti gat or m ust pr o vi de t he m o nit or wit h 
si g ne d a n d date d pri nt o uts. I n a d diti o n, t he rele va nt site staff s h o uld be a vaila ble f or disc ussi o ns 
at m o nit ori n g visits a n d bet wee n m o nit ori n g visits (e. g. , b y tele p h o ne).  
•  Trial m o nit ors will perf or m o n g oi n g s o urce data verificati o n t o c o nfir m t hat data e ntere d i nt o 
t he C R F b y a ut h orise d site pers o n nel are acc urate, c o m plete a n d verifia ble fr o m s o urce 
d oc u me nts , t hat t he safet y a n d ri g hts of s u bjects are bei n g pr otecte d, t o m o nit or dr u g 
acc o u nta bilit y a n d c ollect c o m plete d pa per C R F p a ges, if a p plica ble, a n d t h at t he trial is bei n g 
c o n d ucte d i n acc or da nce wit h t he c urre ntl y  a p pr o ve d pr ot oc ol a n d a n y ot h er trial a gree me nts, 
I C H G C P, a n d all a p plica ble re g ulat or y re q uir e m e nts. 
•  M o nit ori n g will be c o n d ucte d usi n g a ris k -bas e d a p pr oac h i n cl u di n g ris k assess me nt, 
m o nit ori n g pla ns, ce ntr alise d m o nit ori n g (re m ote assess me nt of data b y N o v o N or dis k) a n d 
visits t o sites.  
•  M o nit ors will re vie w t he s u bject’s me dical r ec or ds a n d ot her s o urce data,  e. g., t he diaries t o 
e ns ure c o nsiste n c y a n d/ or i de ntif y o missi o ns c o m pare d t o t he C R F.  
1 0. 1. 8. 3  
Pr ot oc ol c o m pli a nce  
De viati o ns fr o m t he pr ot oc ol s h o ul d b e a v oi de d. If de viati o ns d o occ ur, t h e i n vesti gat or m ust 
i nf or m t he m o nit or wit h o ut dela y a n d t he i m plicati o ns of t he de viati o n m ust be re vie we d a n d 
disc usse d.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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1
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 of
  Pr ot oc ol  versi o n 4. 0
8 0
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
8 1  of 1 1 6  
 
De viati o ns m ust be d oc u me nte d a n d e x plai ne d i n a pr ot oc ol de viati o n b y st ati n g t he reas o n, d ate,  
a n d t he acti o ns ta ke n . S o me de viati o ns, f or w hic h c orrecti o ns are n ot p ossi ble, ca n be 
ac k n o wle d ge d a n d c o nfir me d via e dit c hec ks i n t he C R F or via listi n gs fr o m t he trial data base.   
1 0. 1. 9  
S o urce d oc u me nts  
If s o urce data is e ntere d directl y i n a pa per C R F, eac h d ata e ntr y or clear series of dat a e ntries m ust 
be si g ne d a n d date d s e paratel y b y t he trial staff ma ki n g t he e ntr y.  
•  F or e C R Fs: All data e ntere d i n t he e C R F m ust be verifia ble i n s o urce d oc u me ntati o n ot her t ha n 
t he C R F, e x ce pt f or t he f oll o wi n g data t hat h as bee n rec or de d dir ectl y i nt o t he e C R Fs a n d will 
be c o nsi dere d s o urce dat a:  
•  F or pa p er diari es t he ori gi nal of t he c o m plete d diaries m ust n ot be re m o ve d fr o m t he site, u nless 
t he y f or m part of t h e C R F a n d a c o p y is ke pt at t h e site. 
•  S o urce d oc u me nts pr o vi d e e vi de nce f or t h e e xiste nce of t he s u bject a n d s u bsta ntiate t he 
i nte grit y of t he d ata c ollecte d. S o urce d o c u me nts are file d at t he site. 
•  Data re p orte d o n t he p a p er C R F or e nt ere d i n t he e C R F t hat are tra nscri be d fr o m s o urce 
d oc u me nts m ust be c o nsiste nt w it h t he s o urce d oc u me nts, or t he discre p a ncies m ust be 
e x plai ne d. T he i n vesti gat or ma y n ee d t o r e q uest pr e vi o us me dical rec or ds or tra nsfer rec or ds. 
Als o, c urre nt me dic al rec or ds m ust be a vaila ble.  
•  It m ust be p ossi ble t o verif y s u bject’s me dical hist or y i n s o urce d o c u me nts, s uc h as s u bject’s 
me dical rec or d.  
•  T he i n vesti gat or m ust d oc u me nt a n y atte m pt t o o btai n e xter nal me dical i nf or mati o n b y n oti n g 
t he dates w he n i nf or mati o n was re q u este d, a n d w h o was c o ntact e d. 
•  Defi niti o n of w hat c o nstit utes s o urce data ca n  b e f o u n d i n a s o urce d o c u me nt a gree me nt at eac h 
site. T here will o nl y b e o ne s o urce d o c u me nt defi ne d at a n y ti me f or a n y d ata ele me nt.  
1 0. 1. 1 0  Rete nti o n of cli nic al tri al d oc u me nt ati o n  
•  Rec or ds a n d d o c u me nts, i ncl u di n g si g n e d i nf or me d c o nse nt f or ms, pertai ni n g t o t he c o n d u ct of 
t his trial m ust be retai ne d b y t he i n vesti gat or f or 1 5 years after e n d of trial u nless l ocal 
re g ulati o ns or i nstit uti o nal p olicies re q uire a l o n ger ret e nti o n peri o d. N o rec or ds ma y be 
destr o ye d d uri n g t he rete nti o n peri o d wit h o ut t he writte n  a p pr o val of N o v o N or dis k. N o rec or ds 
ma y b e tra nsf erre d t o a n ot her l ocati o n or part y wit h o ut writte n n otificati o n t o N o v o N or dis k.   
•  T he i n vesti gat or m ust be a ble t o access his/ her trial d oc u me nts wit h o ut i n v ol vi n g N o v o N or dis k 
i n a n y w a y. If a p plica ble, eC R F a n d ot her s u bject data will be pr o vi de d i n a n electr o nic rea d a ble 
f or mat t o t he i n vesti gat or bef ore access is re v o k e d t o t he s yste ms a n d/ or electr o nic de vices 
s u p plie d b y N o v o N or dis k. Site-s pecific C R Fs a n d ot her s u bject data (i n a n electr o nic rea d a ble 
f or mat or as p a per c o pies or pri nts) m ust be retai n e d b y t h e site. A c o p y of all data will be st ore d 
b y N o v o N or dis k.  
•  S u bject’s me dical rec or ds m ust be ke pt f or t he ma xi m u m peri o d per mitte d b y t he h os pital, 
i nstit uti o n or pri vate practice. 
1 0. 1. 1 1  Tri al a n d site  cl os ure 
N o v o N or dis k reser ves t he ri g ht t o cl os e t he site or ter mi nate t he trial at a n y ti me f or a n y reas o n at 
t he s ole discreti o n of N o v o N or dis k. If t he trial is s us pe n de d or ter mi nat e d, t he i n vesti gat or m ust 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
 .
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1
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 of
  Pr ot oc ol  versi o n 4. 0
8 1
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
8 2  of 1 1 6  
 
i nf or m t he s u bjects pr o m ptl y a n d e ns ure a p pro priate t hera p y a n d f oll o w -u p. T he i n vesti gat or a n d/ or 
N o v o N or dis k m ust als o pr o m ptl y i nf or m t he re g ulat or y a ut h orities a n d I R Bs/I E Cs a n d pr o vi de a 
detaile d writte n e x pla nati o n.  
Sites will be cl ose d u p o n trial c o m pleti o n. A site is c o nsi dere d cl os e d w he n all re q uire d d o c u me nts 
a n d trial s u p plies ha ve bee n c ollecte d a n d a site cl os ure visit has bee n perf or me d.  
T he i n vesti gat or ma y i nitiate site cl os ure at a n y ti me, pr o vi de d t here is reas o na ble ca us e a n d 
s ufficie nt n otice is gi ve n i n a d va nce of t he i nte n de d ter mi nati o n. 
Reas o ns f or t he earl y cl os ure of a site b y N o v o N or dis k or i n vesti gat or m a y i ncl u de b ut are n ot 
li mite d t o: 
•  Fail ure of t he i n vesti gat or t o c o m pl y wit h t he pr ot oc ol, t he re q uir e me nts of t he I R B/I E C or l ocal 
healt h a ut h orities, N o v o N or dis k pr oc e d ures or G C P g ui deli nes  
•  I n a de q uat e recr uit me nt of s u bjects b y t he i n vesti gat or 
•  Disc o nti n uati o n of f urt her trial pr o d uct de vel o p me nt.  
1 0. 1. 1 2  Res p o nsi bilities  
T he i n vesti gat or is acc o u nta ble f or t he c o n d uct of t he trial at his/ her site a n d m ust e ns ure a de q u ate 
s u per visi o n of t he c o n d u ct of t he trial at t he site. If a n y tas ks are dele gate d, t he i n vesti gat or m ust 
mai ntai n a l o g of a p pr o priatel y q u alifie d pers o ns t o w h o m he/s he has dele gate d s pecifi e d 
trial-relate d d uties. T h e i n vesti gat or m ust e ns ure t hat t here is a d e q uate a n d d oc u me nte d trai ni n g f or 
all staff partici pati n g i n t he c o n d uct of t he trial. It is t he i n vesti gat or’s res p o nsi bilit y t o s u per vise t h e 
c o n d uct of t he trial a n d t o pr otect t he ri g hts, safet y, a n d well -bei n g of t h e s u bjects.  
A q ualifie d p h ysicia n, w h o is a n i n vesti gat or or a s u b -i n vesti gat or f or t he trial, m ust be res p o nsi ble 
f or all trial-relate d me dical decisi o ns. 
T he i n vesti gat or is res p o nsi ble f or fili n g esse ntial d oc u me nts (i.e. , t h ose d o c u me nts w hic h 
i n di vi d uall y a n d c ollecti v el y p er mit e val uati o n of t he c o n d uct of a trial a n d t he q ualit y of t h e data 
pr o d uce d) i n t he i n v esti gat or trial master file. T h e d oc u me nts, i ncl u di n g t he s u bject i de ntificati o n 
c o de list m ust be ke pt i n a se c ure l oc ke d facilit y s o t hat n o u na ut h orise d pers o ns ca n get access t o 
t he data. 
T he i n vesti gat or will ta ke all necessar y tec h nical a n d or ga nisati o nal safet y meas ures t o pre ve nt 
acci de nt al or wr o n gf ul d estr ucti o n, l oss or deteri orati o n of data. T he i n vesti gat or will pr e ve nt a n y 
u na ut h orise d access t o data or a n y ot her pr ocessi n g of data a gai nst a p plica ble la w. T his als o 
i ncl u des e ns uri n g t hat n o i n direct s hari n g of user cre de ntials f or I T s yste ms use d i n t his st u d y ta kes 
place (e. g., b y n ot s hari n g I T e q ui p me nt wit h ot hers i n a wa y w here us er cre de ntials ha ve t he 
p ossi bilit y of bei n g s h are d). T he i n vesti gat or m ust be a ble t o pr o vi de t he n ecessar y i nf or mati o n or 
ot her wise de m o nstrat e t o N o v o N or dis k t hat s uc h tec h nical a n d or ga nisati o nal safet y meas ures ha v e 
bee n ta ke n.  
D uri n g a n y peri o d of u na vaila bilit y, t he i n vesti gat or m ust dele gate res p o nsi bilit y f or me dical care of 
s u bjects t o a s pecific q u alifie d p h ysicia n w h o will be rea dil y a v aila ble t o s u bjects d uri n g t h at ti me.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
 .
-
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1
 |
 of
  Pr ot oc ol  versi o n 4. 0
8 2
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
8 3  of 1 1 6  
 
If t he i n vesti gat or is n o l o n ger a ble t o f ulfil t he r ole as i n vesti gat or (e. g., if he/s he m o ves or retires), 
a ne w i n vesti gat or will b e a p p oi nte d i n c o ns ultati o n wit h N o v o N or dis k.  
T he i n vesti gat or a n d ot her site pers o n nel m ust ha v e s ufficie nt E n glis h s kills acc or di n g t o t heir 
assi g ne d t as ks.  
1 0. 1. 1 3  I n de m nit y st ate me nt 
N o v o N or dis k carries pr o d uct lia bilit y f or its pr o d ucts, a n d lia bilit y as ass u me d u n der t he s pecial 
la ws, acts a n d/ or g ui deli n es f or c o n d u cti n g cli nical trials i n a n y c o u ntr y, u nless ot hers ha ve s h o w n 
ne gli ge n ce.  
N o v o N or dis k ass u mes n o  lia bilit y i n t he e v e nt of ne gli ge n ce or a n y ot her li a bilit y of t he sites or 
i n vesti gat ors c o n d u cti n g t he trial or b y pers o ns f or w h o m t he sai d site or i n vesti gat or are 
res p o nsi ble. 
1 0. 1. 1 4  P u blic ati o n p olic y  
T he i nf or mati o n o btai ne d d uri n g t he c o n d uct of t his tri al is c o nsi dere d c o nfi de ntial a n d ma y be use d 
b y or o n b e half of N o v o N or dis k f or re g ulat or y p ur p oses as well as f or t he ge n eral d e vel o p me nt of 
t he trial pr o d uct. All i nf or mati o n s u p plie d b y N o v o N or dis k i n c o n necti o n wit h t his trial s hall 
re mai n t he s ole pr o pert y of N o v o N or dis k a n d is t o be c o nsi dere d c o nfi de ntial i nf or mati o n.  
N o c o nfi de ntial i nf or mati o n s hall be discl ose d t o ot hers wit h o ut pri or writte n c o nse nt fr o m 
N o v o  N or dis k. S uc h i nf or mati o n s hall n ot be use d e x ce pt i n t he perf or ma n ce of t his trial.  
T he i nf or mati o n o btai ne d d uri n g t his trial ma y be ma de a vaila ble t o ot her i n vesti gat ors w h o are 
c o n d ucti n g ot h er cli nical trials wit h t he trial pr o d uct, if dee me d necess ar y b y N o v o N or dis k. 
Pr o vi de d t hat certai n c o n diti o ns are f ulfille d, N o v o N or dis k ma y gra nt access t o i nf or mati o n 
o btai ne d d uri n g t his trial t o researc hers w h o re q uire access f or researc h pr oj ects st u d yi n g t he sa m e 
disease a n d/ or tri al pr o d u ct st u die d i n t his trial.  
N o v o N or dis k ma y p u blis h o n its cli nical trials we bsite a re dacte d C T R f or t his trial. 
O ne i n vesti gat or will be a p p oi nte d b y N o v o N or dis k t o re vie w a n d si g n t he C T R (si g nat or y 
i n vesti gat or) o n b e half of all partici pati n g i n v esti gat ors. T he si g nat or y i n vesti gat or will be 
a p p oi nte d base d u p o n criteria defi n e d b y t he I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors 
f or res earc h p u blicati o n5 1. 
1 0. 1. 1 4. 1  
C o m m u nic ati o n of res ults  
N o v o N or dis k c o m mits t o c o m m u nicate a n d discl ose res ults of trials re gar dless of o utc o me. 
Discl os ure i ncl u des p u bli cati o n of a ma n us cri pt i n a peer -re vi e we d s cie ntific j o ur nal, a bstract 
s u b missi o n wit h a p oster or oral pres e ntati o n at a s cie ntific meeti n g or discl os ure b y ot her mea ns.  
T he re s ults of t his trial will be s u bject t o p u blic discl os ure o n e xter nal we b sites acc or di n g t o 
i nter nati o nal a n d nati o nal re g ulati o ns. N o v o N or dis k reser ves t he ri g ht t o defer t h e release of data 
u ntil s pecifie d milest o nes are reac he d, f or e x a m ple w he n t he C T R is a vaila ble. T his i ncl u des t he 
ri g ht n ot t o rele ase t he res ults of i nteri m a nal yses, beca use t h e rel ease of s uc h i nf or mati o n ma y 
i nfl ue nce t he res ults of t he e ntire trial. 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
8 3
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
8 4  of 1 1 6  
 
At t he e n d of t he trial, o n e or m ore sci e ntific p u blicati o ns ma y b e pre pare d c oll a b orati vel y b y t he 
i n vesti gat or(s) a n d N o v o N or dis k. N o v o N or dis k reser ves t he ri g ht t o p ost p o ne p u blicati o n a n d/ or 
c o m m u nicati o n f or u p t o 6 0 da ys t o pr ot ect i ntellect ual pr o pert y.  
I n all cases, t he trial res ults will be re p orte d i n a n o bjecti ve, acc urat e, bala nce d a n d c o m plete 
ma n ner, wit h a disc ussi o n of t he stre n gt hs a n d li mitati o ns. I n t he e v e nt of a n y disa gree me nt o n t he 
c o nte nt of a n y p u blicati o n,  t he o pi ni o ns of b ot h t he i n vesti gat ors a n d N o v o N or dis k will be fairl y 
a n d s ufficie ntl y re pres e nte d i n t he p u blicati o n.  
1 0. 1. 1 4. 2  
A ut h ors hi p  
N o v o N or dis k will w or k wit h o ne or m ore i n vesti gat ors a n d ot her e x perts w h o ha ve c o ntri b ute d t o 
t he trial c o nce pt or desi g n, ac q uisiti o n, a nal ysis or i nter pretati o n of dat a t o re p ort t he res ults i n o ne 
or m ore p u blicati o ns.  
A ut h o rs hi p of p u blicati o ns s h o ul d be i n acc or da n ce wit h t he Rec o m me n d ati o ns f or t he C o n d uct, 
Re p orti n g, E diti n g a n d P u blicati o n of Sc h olarl y W or k i n Me dical J o ur nals b y t he I nt er nati o nal 
C o m mittee of Me dical J o ur nal E dit ors 5 1 ,5 2. 
All a ut h ors will be pr o vi de d wit h t he rele va nt statistical ta bles, fi g ures, a n d re p orts nee d e d t o 
e val uate t he pla n n e d p u blicati o n.  
W here re q uir e d b y t he j o ur nal, t he i n vesti gat or  fr o m eac h site will be na me d i n a n 
ac k n o wle d ge me nt or i n t he s u p ple me ntar y mat eri al, as s pecifie d b y t h e j o ur nal.  
1 0. 1. 1 4. 3  
Site -s pecific p u blic ati o n(s) b y i n vesti g at or(s) 
F or a m ulti -ce ntre cli nic al trial, a nal ys es base d o n si n gle -site dat a us uall y h a ve si g nifica nt statistical 
li mitati o ns a n d fre q ue ntl y d o n ot pr o vi de mea ni n gf ul i nf or m ati o n f or healt hcare pr ofessi o nals or 
s u bjects, a n d t heref ore m a y n ot b e s u p p orte d b y N o v o N or dis k. T h us, N o v o N or dis k ma y d e n y a 
re q uest or as k f or defer m e nt of t he p u blicati o n of i ndi vi d ual site res ults u ntil t he pri mar y ma n uscri pt 
is acce pte d f or p u blicati o n. I n li ne wit h G o o d P u blicati o n Practice, s u c h i n di vi d ual re p orts s h o ul d 
n ot prece d e t he pri mar y ma n uscri pt a n d s h o ul d al wa ys refere nce t h e pri mar y ma n us cri pt of t he trial.  
1 0. 1. 1 4. 4  
I n vesti g at or access t o d at a a n d re vie w of res ults 
As o w ner of t h e trial data base, N o v o N or dis k h as t he discreti o n t o deter mi n e w h o will ha ve access 
t o t he data base. 
I n di vi d ual i n vesti gat ors will ha ve t heir o w n researc h s u bjects’ d ata a n d will be pr o vi de d wit h t he 
ra n d o misati o n c o de after res ults are a vaila ble. 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
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 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
8 4
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
8 5  of 1 1 6  
 
1 0. 2  A p pe n di x 2: Cli nic al l a b or at or y tests  
•  T he tests detaile d i n Ta bl e  1 0 -1  a nd T a ble  1 0 -2  will be perf or me d b y t h e ce ntral la b orat or y, 
e x ce pt f or t he f oll o wi n g w hic h will be perf or me d at a s pecialise d la b orat or y:  
•  N N C 0 1 6 5 -1 8 7 5 plas ma c o nce ntrati o n  
•  Se ma gl uti de plas ma c o nce ntrati o n  
•  N N C 0 1 6 5 -1 8 7 5 a nti b o dies (cr oss reacti vit y a n d n e utralisi n g effect ) 
•  Le pti n  
•  S ol u ble le pti n rece pt or  
•  A d diti o nal tests ma y be p erf or me d at a n y ti me d uri n g t he trial as deter mi ne d necessar y b y t he 
i n vesti gat or or re q uir e d b y l oc al re g ulati o ns. O nl y la b orat or y sa m ples s pecifie d i n t he pr ot oc ol 
s h o ul d be se nt t o t he ce ntral la b orat or y f or a n al ysis; if a d diti o nal la b orat or y sa m pli n g is nee d e d, 
e. g., t o f oll o w u p o n A Es, t his m ust be d o ne at a l ocal la b orat or y. 
•  T he ce ntr al la b orat or y will c o m m u nicate t o t he i n vesti gat or a b n or mal val u es of para met ers n ot 
re q ueste d i n t he pr ot o c ol b ut i de ntifie d b y t he la b orat or y e q ui p me nt a n d/ or t heir pr ocesses 
acc or di n g t o t heir l a b S O Ps. T hese data will n ot be tra nsferre d t o t he trial d ata base. T h e 
i n vesti gat or s h o ul d r e vie w s uc h val ues f or A Es a n d re p ort t hese acc or di n g t o t his pr ot oc ol. 
•  T he i n vesti gat or m ust re vie w all la b orat or y res ults f or c o nc o mita nt ill nesses a n d  A Es.  
•  La b orat or y s a m ples will be destr o ye d n o lat er t ha n at fi nalisati o n of t he C T R, e x ce pt bi osa m ples 
f or f ut ure a nal ysis a n d sa m ples f or meas ure me nts of N N C 0 1 6 5-1 8 7 5 plas m a c o nce ntrati o n, 
se ma gl uti de plas m a c o nce ntrati o n a n d N N C 0 1 6 5-1 8 7 5 a nti b o dies.  
•  F or hae mat ol o g y s a m ples ( differe ntial c o u nt) w here t he test res ult is n ot n or mal, t he n a part of 
t he sa m ple ma y be ke pt f or u p t o t w o years or acc or di n g t o l ocal re g ulati o ns. 
•  H u ma n bi osa m ples f or rete nti o n will be st ore d as descri be d i n A p p e n di x 8, Secti o n 1 0. 8 . 
T a ble  1 0 -1  
Pr ot oc ol -re q uire d effic ac y l a b or at or y  assess me nts  
L a b or at or y assess me nts  
P ar a meters  
Gl uc ose meta b olis m  
 
•  
Fasti n g plas ma gl uc ose ( F P G)  
•  
H b A 1c 
•  
Gl uca g o n 1 
•  
H O M A B  
•  
H O M A A i ns uli n resista nce  
•  
Fasti n g i ns uli n  
Li pi ds  
 
•  
T otal C h olester ol  
•  
Hi g h de nsit y li p o pr otei n ( H D L) c h olester ol  
•  
L o w de nsit y li p o pr otei n ( L D L) c h olester ol  
•  
Ver y l o w -de nsit y li p o pr otei n ( V L D L) c h olester ol 
•  
Tri gl yceri de  
•  
Free Fatt y Aci ds ( F F A)s  
N otes : 
1 Res ults o btai ne d usi n g assa ys f or researc h use o nl y will be re p orte d directl y t o N o v o N or dis k.  
 
 
 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
8 5
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
8 6  of 1 1 6  
 
T a ble  1 0 -2  
Pr ot oc ol -re q uire d s af et y l a b or at or y assess me nts 
L a b or at or y assess me nts  
P ar a meters  
Hae mat ol o g y  
 
•  Hae m o gl o bi n  
•  Le u k oc ytes  
•  T hr o m b oc ytes  
•  Er yt hr oc ytes  
•  Differe ntial c o u nt (a bs ol ute):  
•  E osi n o p hils  
•  Ne utr o p hils  
•  B as o p hils  
•  L y m p h oc ytes  
•  M o n oc ytes  
Bi oc he mistr y 1  
 
•  Ala ni ne A mi n otr a nsferase ( A L T) 1 
•  Al b u mi n  
•  Al kali ne p h os p hatase  
•  As partate A mi n otra nsferase ( A S T) 1 
•  Creati ni ne  
•  P otassi u m  
•  P h os p hate  
•  S o di u m  
•  T otal Bilir u bi n 1 
•  T otal Calci u m  
•  G G T  
•  A m ylase  
•  Li pase  
•  Hs C R P  
•  Ma g nesi u m  
•  Ser u m t otal pr otei n 
•  Bl o o d urea nitr o ge n ( B U N) test  
H or m o nes  
 
•  T h yr oi d sti m ulati n g h or m o ne  ( T S H) 
•  A nti di uretic H or m o ne  ( A D H) 
•  P arat h yr oi d h or m o ne, i ntact ( P T H)  
•  C ortis ol  
•  Calcitri ol 1, 2 5 Di h y dr o x y (Vit a mi n D)  
•  Estra di ol  
•  Pr olacti n  
•  F ollicle -sti m ulati n g h or m o ne ( F S H) 
•  L utei nizi n g h or m o ne  
•  T est oster o ne t otal 
•  2 5 -h y dr o x y -vita mi n D  
•  I G F-1  
Bi o mar kers  
 
•  S ol u ble  Le pti n Rece pt or 2 
•  Le pti n 2 
•  Pr ostate S pecific A nti ge n ( P S A)  
A nti b o dies  
 
•  A nti -N N C 0 1 6 5 -1 8 7 5 a nti b o d y (titre)  
•  A nti -N N C 0 1 6 5 -1 8 7 5 a nti b o d y ( p os/ ne g)  
•  A nti -N N C 0 1 6 5 -1 8 7 5 bi n di n g a nti b o dies cr oss -reacti n g wit h P Y Y3 -3 6 ( p os/ ne g) 
•  A nti P Y Y 3 -3 6 Ne utralisi n g A nti b o dies  
C oa g ulati o n P ara meter  
 
•  P T a n d I N R  
•  Fi bri n o ge n  
•  A P T T  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
8 6
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
8 7  of 1 1 6  
 
Pre g na nc y testi n g  
Meas ure d at all cli nic visits  
•  Hi g hl y se nsiti ve  uri ne  pre g na nc y test (as nee de d f or w o me n of c hil d beari n g 
p ote ntial)  
Uri nal ysis  
 
•  Calci u m  
•  S o di u m  
•  P otassi u m  
•  C ortis ol, free  
•  Creati ni ne  
•  Al b u mi n  
•  C ortis ol/creati ni ne  
•  Al b u mi n/creati ni ne  
•  Ne utr o p hil gelati nase -ass oc iat e d li p ocali n/creati ni ne3 
2 4 -h o ur uri ne  
 
•  Ti me of c ollecti o n  
•  Calci u m  
•  S o di u m  
•  P otassi u m  
•  C ortis ol, free  
•  Creati ni ne  
•  Al b u mi n  
•  C ortis ol/creati ni ne  
•  Al b u mi n/creati ni ne  
•  V ol u me  
•  Creati ni ne cleare nce  
Ot her tests  
  
•  e G F R calc ulate d b y t he ce ntral la b orat or y base d o n t he creati ni ne val ue usi n g 
t he C K D-E PI e q uati o n  
•  N N C 0 1 6 5 -1 8 7 5 plas ma c o nce ntrati o n  
•  Se ma gl uti de plas ma c o nce ntrati o n  
•  Bi osa m ples f or f ut ure a nal ysis  
•  ser u m ( part 1 : V 2, V 1 0) ; ( part 2 : V 2, V 8, V 1 2, V 1 6) 
•  plas ma ( P art 1  : V 2, V 1 0) ; (P art 2  : V 2, V 8, V 1 2, V 1 6) 
•  D N A ( V 2 f or b ot h P art 1  a n d P art 2 ) 
N otes:  
1 Details of re q uire d acti o ns a n d f oll o w -u p assess me nts f or i ncrease d li ver para meters i ncl u di n g a n y disc o nti n uati o n 
criteria are gi ve n i n Secti o n 1 0. 3  ( H y’s La w) a n d Secti o n 7. 1 . 
2 Res ults fr o m b i o marker assa ys relate d t o h u n ger a n d satiet y, f or researc h use o nl y , will b e re p orte d directl y t o N o v o 
N or dis k.  
3 Res ults o btai ne d usi n g a ssa y f or researc h use o nl y will be re p orte d directl y t o N o v o N or dis k. 
La b orat or y/a n al yt e res ults t hat c o ul d u n bli n d t he trial ( N N C 0 1 6 5 -1 8 7 5 plas ma c o nce ntr ati o n, 
se ma gl uti de plas m a c o nce ntrati o n a n d N N C 0 1 6 5-1 8 7 5 a nti b o dies) will n ot be re p ort e d t o t he sites . 
F urt her m ore, t he ass a ys use d f or gl uca g o n, n e utr o p hil gelati nase -ass oci ate d li p ocali n/creati ni ne, 
s ol u ble le pti n rece pt or a n d le pti n are f or researc h use o nl y, h e nce t hes e res ults will n ot be re p orte d 
t o t he sites, b ut will be re p orte d directl y t o N o v o N or dis k. 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
 .
-
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1
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 of
  Pr ot oc ol  versi o n 4. 0
8 7
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
8 8  of 1 1 6  
 
1 0. 3  A p pe n di x 3: A d verse e v e nts: Defi niti o ns a n d pr oce d ures f or rec or di n g, e v al u ati o n, 
f oll o w-u p, a n d re p orti n g  
1 0. 3. 1  
Defi niti o n of A E  
A E defi niti o n  
A n A E is a n y u nt o war d me dical occ urre n ce i n a cli nical trial s u bject t hat is te m p orall y ass ociate d 
wit h t he use of a n  i n vesti gati o nal me di ci nal pr o d u ct (I M P), w het her or n ot c o nsi dere d relate d t o 
t he I M P. 
A n A E ca n t h eref ore b e a n y u nfa v ora bl e a n d u ni nt e n de d si g n, i ncl u di n g a n a b n or mal la b orat or y 
fi n di n g, s y m pt o m or dise ase ( ne w or e x acer bate d) te m p orall y ass ociate d wit h t he use of a n I M P. 
 
E ve nts meeti n g  t he A E defi niti o n 
•  A n y a b n or mal la b orat or y test res ults or safet y ass ess me nts c o nsi dere d cli nicall y si g nifica nt i n 
t he me dical a n d sci e ntific j u d g me nt of t h e i n vesti gat or, i n cl u di n g e ve nts t h at ha ve w ors e ne d 
fr o m pri or t o t he ti me p oi nt fr o m w hic h A Es are c ollecte d 
•  C o n diti o ns detecte d or dia g n os e d aft er I M P a d mi nistrati o n e ve n t h o u g h it ma y h a ve bee n 
prese nt pri or t o t he ti me p oi nt fr o m w hic h A Es are c ollecte d  
•  E x acer bati o n/ w orse ni n g of a c hr o ni c or i nter mitte nt c o n diti o n i ncl u di n g eit her a n i ncreas e i n 
fre q ue n c y a n d/ or i nte nsit y of t he c o n diti o n 
•  Si g ns, s y m pt o ms or t he cli nical se q uelae of a s us p ecte d dr u g -dr u g i nteracti o n  
•  Si g ns, s y m pt o ms or t he cli nical se q uelae of a s us p ecte d o ver d ose of I M P re gar dless of i nte nt  
A “lac k of effi cac y ”  or “fail ure of e x pecte d p har m ac ol o gical acti o n” per se will n ot be re p orte d as 
a n A E or S A E. S uc h i nsta nces will be ca pt ure d i n t he efficac y assess me nts. H o we ver, t he si g ns, 
s y m pt o ms a n d/ or cli nical se q uelae res ulti n g fr o m lac k of efficac y wi ll be re p orte d as A E or S A E 
if t he y f ulfil t he defi niti o n. 
E ve nts N O T  meeti n g t he A E defi niti o n  
•  C o n diti o ns prese nt pri or t o t he ti me p oi nt fr o m w hic h A Es are c ollecte d a n d a ntici pate d 
da y -t o-da y fl u ct uati o ns of t hese c o n diti o ns, i ncl u di n g t h ose i de ntifie d d uri n g scree ni n g or 
ot her trial pr oce d ures p erf or me d bef ore e x p os ure t o I M P.   
•  N ote: C o n diti o ns prese nt or occ urri n g pri or t o t he ti me p oi nt fr o m w hic h A Es are c ollecte d 
s h o ul d be rec or de d as c o nc o mita nt ill ness/ me dical hist or y.  
•  Me dical or s ur gic al pr oce d ures ( e. g. , e n d osc o p y, a p pe n dect o m y). T he c o n diti o n t hat lea ds t o 
t he pr oce d ure is t he A E. 
•  Me dical or s ur gic al pr oce d ures n ot prece d e d b y a n A E or w orse ni n g of a k n o w n c o n diti o n.  
1 0. 3. 2  
Defi niti o n of a n S A E  
A n S A E is a n A E t h at f ulfils at le ast o ne of t he f oll o wi n g criteri a:  
a. Res ults i n de at h  
b. Is life -t hre ate ni n g 
T he ter m ‘life-t hreat e ni n g’ i n t he d efi niti o n of ‘seri o us’ refers t o a n e ve nt i n w hic h t he s u bject 
was at ris k of deat 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 hi c h h y p ot h eticall y 
mi g ht ha ve ca use d d eat h, if it were m ore s e vere.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
8 8
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
8 9  of 1 1 6  
 
c. Re q uires i n p atie nt h os pit alis ati o n or pr ol o n g ati o n of e xisti n g h os pit alis ati o n  
•  H os pitalisati o n si g nifies t hat t he s u bject has bee n detai ne d at t he h os pital or e mer ge nc y war d 
f or o bser vati o n a n d/ or treat me nt t hat w o ul d n ot ha ve bee n a p pr o priat e i n t he p h ysici a n’s 
office or o ut p atie nt setti n g. C o m plicati o ns t hat occ ur d u ri n g h os pitalisati o n are A Es. If a 
c o m plicati o n pr ol o n gs h os pitalisati o n or f ulfils a n y ot her s eri o us ness criteria, t he e ve nt is 
seri o us. W he n i n d o u bt as t o w het her “ h os pitalisati o n” occ urre d or was necessar y, t he A E 
s h o ul d be c o nsi dere d s eri o us. 
•  H os pital isati o n f or electi ve treat me nt ( e. g., electi ve me dical or s ur gi cal pr o ce d ures) of a 
c o n diti o n t hat was prese nt pri or t o t he ti me p oi nt fr o m w hic h A Es are c ollecte d, a n d t hat di d 
n ot w orse n, is n ot c o nsi dere d a n A E.  
N ote:  
•  H os pitalisati o ns f or a d mi nistrati ve, trial relate d, s o cial a n d c o n v e nie nce reas o ns d o n ot 
c o nstit ute A Es a n d s h o ul d t heref ore n ot be re p orte d as A Es or S A Es.  
•  H os pital a d missi o ns f or me dical or s ur gical pr oce d ures, pla n ne d b ef ore trial i ncl usi o n, are n ot 
c o nsi dere d A Es or S A Es.   
d. Res ults i n persiste nt or si g nific a nt dis a bilit y/i nc a p acit y  
•  T he ter m disa bilit y me a ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y t o c o n d uct n or mal life 
f u ncti o ns. 
•  T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie n ce of relati vel y mi n or me dical si g nifica nce, 
s uc h as u nc o m plicate d h ea dac he, na us ea, v o miti n g, diarr h oea, i nfl ue nza, a n d acci de nt al 
tra u ma (e. g., s prai ne d a n kle), w hic h ma y i nterfere wit h or pre ve nt e ver y da y life f u ncti o ns b ut 
d o n ot c o nstit ute a s u bsta ntial disr u pti o n.  
e. Is a c o n ge nit a l a n o m al y/ birt h defect 
f. I m p ort a nt me dic al e v e nt: 
•  Me dical or scie ntifi c 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 S A E re p orti n g is 
a p pr o priate i n ot her sit uati o ns. T his i ncl u des 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 pitalisati o n b ut ma y je o par dise t he 
s u bject or ma y re q uire m e dical or s ur gical i nter ve nti o n t o pre ve nt o ne of t h e ot her o utc o mes 
liste d i n t he a b o ve defi niti o n. T hese e ve nts s h o ul d us uall y be c o nsi dere d s eri o us a n d re p orte d 
as S A Es usi n g t he i m p ort a nt me dical e ve nt criteri o n. 
•  T he f oll o wi n g a d vers e e v e nts m ust al wa ys b e re p orte d as S A Es usi n g t h e i m p orta nt me dical 
e ve nt criteri o n if n o ot her seri o us ness criteria are a p plica ble:  
•  S us pici o n of tra ns missi o n of i nfecti o us a ge nts via t he I M P  
•  Ris k of li ver i nj ur y defi ne d as ala ni ne a mi n otra nsferase ( A L T) or as partate a mi n otra nsferase 
( A S T) > 3 x U N L a n d t otal bilir u bi n > 2 x U N L w here n o alter nati ve aeti ol o g y e xists ( H y’s 
la w). 
 
1 0. 3. 3  
Descri pti o n of A Es re q uiri n g a d diti o n al d at a c ollecti o n  
Descri pti o n of A Es re q uiri n g a d diti o n al d at a c ollecti o n ( o n s pecific e ve nt f or m)  
A d verse e v e nts re q uiri n g a d diti o n al d at a c ollecti o n  
A Es re q uiri n g a d diti o nal data c ollecti o n are A Es w here t he a d diti o nal data will be nefit t he 
e val uati o n of t he safet y of t h e trial pr o d ucts (s ee T a ble  8 -1 ). T h e selecti o n of t hese e v e nts is 
base d o n t he n o n -cli nical a n d cli nical data wit h N N C 0 1 6 5 -1 8 7 5 a n d se ma gl uti de, k n o wle d ge 
fr o m t he G L P-1 R A dr u g class as well as re g ulat or y re q uire me nts.  
Me d ic ati o n err o r 
A me dicati o n err or is a n u ni nte n de d fail ure i n t he I M P treat me nt pr ocess t hat lea ds t o, or has t he 
p ote ntial t o lea d t o, har m t o t he s u bject, s uc h as:  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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V V- T M F- 5 0 4 2 3 4 5
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
9 0  of 1 1 6  
 
•  a d mi nistrati o n of wr o n g dr u g  
N ote: Use of wr o n g D U N is n ot c o nsi dere d a me dicati o n err or u nl ess it res ults i n 
a d mi nistrati o n of wr o n g dr u g.  
•  wr o n g r o ute of a d mi nistrati o n, s uc h as i ntra m usc ular i nstea d of s u bc ut a ne o us  
•  acci de nt al a d mi nistrati o n of  hi g her d ose t ha n i nte n de d. T he a d mi nistere d d ose m ust de viate 
fr o m t he i nte n de d d ose t o a n e xte nt w here cli nical c o nse q ue nces f or t h e trial s u bject were 
li kel y t o ha p pe n as j u d ge d b y t he i n vesti gat or, alt h o u g h t he y di d n ot necess aril y o cc ur. 
M isse d d oses or dr u g pa uses are n ot t o be re p orte d as a me dicati o n err or. 
Mis use a n d a b use   
•  Sit uati o ns w here t he I M P is i nte nti o nall y a n d i na p pr o priatel y use d n ot i n acc or da nce wit h t he 
pr ot oc ol (e. g. , o ver d ose t o ma xi mise effect)  
•  Persiste nt or s p ora dic, i nt e nti o nal e xcessi ve use of a n I M P w hic h is acc o m pa nie d b y har mf ul 
p h ysical or ps yc h ol o gical effects (e. g. , o v er d ose wit h t he i nte nti o n t o ca use har m)  
Me dicati o n err or, mis use a n d a b use m ust al wa ys b e re p ort e d as a n A E (e. g. , acci de nt al o ver d ose, 
i nte nti o nal o ver d ose or ot her) o n a se p arate A E f or m, a n d a me dicati o n err or, mis use a n d a b use 
f or m m ust be c o m plete d. I n case of a me dicati o n err or a n d/ or mis use a n d a b use res ulti n g i n a 
cli nical c o nse q ue n ce (e. g. , h y p o gl ycae mia or ot her), t his m ust be re p orte d o n a n a d diti o nal A E 
f or m. 
Ac ute g all bl a d der d ise ase 
E ve nts of s y m pt o matic ac ute gall bla d der dis ease (i ncl u di n g gall st o nes a n d c h olec ystitis). 
He p atic e ve nt  
He patic e v e nt defi ne d as:  
•  Dis or ders of t he li ver i ncl u di n g c h olestatic c o n diti o ns a n d li ver -relate d si g ns a n d s y m pt o ms 
•  A L T or A S T > 3 x U N L a n d t otal bilir u bi n > 2 x U N L or I N R > 1. 5 *  
•  A L T or A S T > 3 x U N L wit h t he a p peara nce of fati g ue, na us ea, v o miti n g, ri g ht u p per q u a dra nt 
pai n or te n der ness, fe v er, ras h, a n d/ or e osi n o p hilia ( > 5 %)  
* Please n ote t hat i n cas e of a he patic e ve nt defi ne d as A L T or A S T > 3 x U N L a n d t otal bilir u bi n 
> 2 x U N L, w h ere n o alter nati ve aeti ol o g y e xists ( H y’s l a w), t his m ust be re p orte d as a n S A E 
usi n g t he i m p orta nt me di cal e ve nt criteri o n if n o ot her seri o us ness criteria are a p plica bl e.  
M ali g n a nt n e o pl as m  
Mali g na nt ne o pl as m b y hist o pat h ol o g y or ot her s u bsta ntial cli nical e vi de nce.  
Ac ute p a ncre ati tis  
Dia g n osis of p a ncreatitis re q uires t w o of t h e f oll o wi n g t hree feat ures:  
1.  a b d o mi nal pai n c o nsiste nt wit h pa ncreatitis ( o nset of a persiste nt, se v ere, e pi gastric pai n ofte n 
ra diati n g t o t he b ac k) 
2.  ser u m li pase acti vit y (a n d/ or a m ylas e acti vit y) at l east three ti mes greater t ha n t he U N L o f 
n or mal  
3.  c haracteristic fi n di n gs of pa ncreatitis o n i ma gi n g.  
Ac ute ki d ne y i nj ur y  
E ve nts of a br u pt or ra pi d decli ne i n re n al filtrati o n rate. T his c o n diti o n is us uall y c h aracterise d b y 
a rise i n ser u m creati ni ne c o nce ntr ati o n or b y azet o mia (a rise i n bl o o d urea nitr o ge n ( B U N) 
c o nce ntr ati o n).  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
9 1  of 1 1 6  
 
Ac ute ki d ne y i nj ur y defi ne d as:  
1.  I n crease i n ser u m creati ni ne ≥ 0. 3 m g/ d L wit hi n 4 8 h o urs 
2.  I n crease i n ser u m creati ni ne t o ≥ 1. 5 ti mes baseli ne wit hi n 7 da ys 
3.  Uri ne v ol u me < 0. 5  m L/ k g/ h f or 6 h o urs  
4.  Ot her  
I njecti o n site re acti o ns 
Please refer t o Secti o n 8. 2. 6  f or m ore d etails o n i njecti o n site reacti o ns. 
 
1 0. 3. 4  
Rec or di n g a n d f oll o w -u p of A E a n d/ or S A E  
A E a n d S A E rec or di n g  
•  T he i n vesti gat or will rec or d all rele va nt A E/ S A E i nf or mati o n i n t he C R F.  
•  T he i n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, s y m pt o ms, 
a n d/ or ot her cli nic al i nf or mati o n. I n s u c h cas es, t he dia g n osis ( n ot t he i n di vi d ual 
si g ns/s y m pt o ms) will be d oc u me nte d as t he A E/ S A E. 
•  W he n a n A E/ S A E occ urs, it is t he  res p o nsi bilit y of t he i n vesti gat or t o re vie w all 
d oc u me ntati o n (e. g. , h os pital pr o gress n otes, la b orat or y a n d dia g n ostics re p orts) relate d t o t he 
e ve nt.  
•  T here ma y b e i nsta nces w he n c o pies of s o urce d o c u me nts (e. g. , me dical rec or ds) f or certai n 
cases are re q ueste d b y N o v o N or dis k. I n s uc h cas es, all s u bject i de ntifiers, wit h t he e x ce pti o n 
of t he s u bject n u m ber, will be re dact e d o n t he c o pi es of t he s o urce d oc u me nts bef ore 
s u b missi o n t o N o v o N or dis k. 
•  F or all n o n -s eri ous A Es, t he a p plica ble f or ms s h o ul d be si g ne d w he n t he e ve nt is res ol ve d or 
at t he e n d of t he tri al at t he latest. F or si g n -off of S A E relate d f or ms, refer t o “ A E a n d S A E 
re p orti n g via pa p er C R F” later i n t his secti o n. 
•  N o v o N or dis k pr o d ucts use d as c o nc o mi ta nt me di cati o n: if a n A E is c o nsi d ere d t o ha ve a 
ca usal r elati o ns hi p wit h a N o v o N or dis k mar ket e d pr o d uct use d as  c o nc o mita nt me dicati o n i n 
t he trial, it is i m p orta nt t hat t he s us pecte d relati o ns hi p is re p orte d t o N o v o N or dis k, e. g., i n t he 
alter nati ve ae ti ol o g y secti o n o n t he safet y i nf or mati o n f or m. N o v o N or dis k ma y n ee d t o 
re p ort t his a d vers e e ve nt t o rele va nt r e g ulat or y a ut h orities. 
 
Assess me nt of se verit y  
T he i n vesti gat or will assess se verit y f or eac h e ve nt re p orte d d uri n g t he tri al a n d assi g n it t o  o ne of 
t he f oll o wi n g cate g ori es: 
•  Mil d : A n e ve nt t hat is easil y t olerate d b y t h e s u bject, ca usi n g mi ni mal disc o mf ort a n d n ot 
i nterferi n g wit h e v er y da y acti vities. 
•  M o der ate : A n e ve nt t hat ca uses s ufficie nt disc o mf ort a n d i nterferes wit h n or mal e ver y d a y 
acti vities. 
•  Se vere : A n e ve nt t hat pr e ve nts n or mal e ver y da y acti vities.  
N ote: A n A E t hat is assesse d as se vere s h o ul d n ot be c o nf use d wit h a S A E. B ot h A Es a n d 
S A Es ca n be ass esse d as se vere.  
 
Assess me nt of c a us alit y  
•  T he i n vesti gat or is o bli gate d t o asses s t he relati o ns hi p bet wee n I M P a n d t he occ urre nce of 
eac h A E/ S A E.  
N N 9 7 7 5- 4 7 0 8
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
9 2  of 1 1 6  
 
•  Relati o ns hi p bet wee n a n A E/ S A E a n d t he rele va nt I M P(s) s h o ul d be assess e d as:   
•  Pr o ba ble –  G o o d reas o n a n d s ufficie nt d oc u m e ntati o n t o ass u me a ca usal r elati o ns hi p.  
•  P ossi ble –  A ca usal relati o ns hi p is c o ncei va ble a n d ca n n ot be dis misse d.  
•  U nli kel y –  T he e ve nt is m ost li kel y relate d t o aeti ol o g y ot her t ha n t h e I M P.  
•  Alter nati ve aeti ol o g y, s u c h as u n derl yi n g diseas e(s), c o nc o mita nt me dicati o n, a n d ot her ris k 
fact ors, as well as t he te m p oral relati o ns hi p of t h e e ve nt t o I M P a d mi nistrati o n, will be 
c o nsi dere d a n d i n vesti gate d.  
•  T he i n vesti gat or s h o ul d use t he In vesti gat or’s Br oc h ure  f or t he assess m e nt. F or eac h 
A E/ S A E, t he i n vesti gat or m ust d oc u me nt i n t he me dical rec or ds t hat he/s h e has re vie we d t he 
A E/ S A E a n d has pr o vi de d a n assess me nt of ca usalit y.  
•  T here ma y b e sit uati o ns i n w hic h a n S A E has occ urre d, a n d t h e i n vesti gat or has mi ni mal 
i nf or mati o n t o i ncl u de i n t he i nitial re p ort. H o we v er, it is i m p ort a nt t h at t he i n vesti g at or 
al w a ys m a kes a n assess me nt of c a us alit y f or e ver y e v e nt bef ore t he i niti al tr a ns missi o n 
of t he S A E d at a.  
•  T he i n vesti gat or ma y c h a n ge his/ her o pi ni o n of ca usalit y, i n li g ht of f oll o w -u p i nf or mati o n, 
a n d u p date t he ca usalit y assess me nt i n t he C R F.  
•  T he ca us alit y ass ess me nt is o ne of t he criteria use d w he n deter mi ni n g re g ulat or y re p orti n g 
re q uire me nts. 
Fi n al o utc o me  
T he i n vesti gat or will select t he m ost a p pr o priate o utc o me:  
•  Rec o vere d/res ol ve d:  T h e s u bject has f ull y rec o vere d, or b y me dical or s ur gical treat me nt t he 
c o n diti o n has ret ur ne d t o t he le vel o bser v e d w he n first d oc u me nte d  
•  Rec o veri n g/res ol vi n g:  T he c o n diti o n is i m pr o vi n g, a n d t h e s u bject is e x pecte d t o rec o v er 
fr o m t he e ve nt. T his ter m ma y b e a p plica bl e i n cas es of c hr o nic c o n diti o ns, ca ncer or A Es 
o n g oi n g at ti me of deat h ( w here deat h is d ue t o a n ot her A E).   
•  N ote: F or S A Es, t his ter m is o nl y a p plica ble if t h e s u bject has c o m plet e d t he f oll o w -u p peri o d 
a n d is e x pecte d t o rec o v er.  
•  Rec o vere d/res ol ve d wit h se q uel ae:  T he s u bject has rec o v ere d fr o m t he c o n diti o n b ut wit h 
lasti n g effect d u e t o a dis ease, i nj ur y, treat me nt or pr oce d ure. If a se q uel a meets a n S A E 
criteri o n, t he A E m ust be re p orte d as a n S A E.  
•  N ot rec o vere d/ n ot res ol ve d:  T he  c o n diti o n of t he s u bject has n ot i m pr o ve d, a n d t he 
s y m pt o ms are u n c ha n ge d, or t he o utc o me is n ot k n o w n.  
N ote: T his ter m ma y b e a p plica ble i n cases of c hr o nic c o n diti o ns, ca ncer or A Es o n g oi n g at 
ti me of deat h ( w h ere d eat h is d ue t o a n ot her A E).  
•  F at al:  T his ter m is o nl y a p plica ble if t he s u bject die d fr o m a c o n diti o n rel ate d t o t he re p orte d 
A E. O utc o mes of ot her re p orte d A Es i n a s u bject bef ore h e/s he die d s h o ul d be assesse d as 
“rec o v ere d/res ol ve d ”, “rec o veri n g/res ol vi n g”, “rec o vere d/r es ol ve d wit h se q uela e” or “ n ot 
rec o vere d/ n ot res ol v e d”. A n A E wit h a fat al o utc o me m ust be re p orte d as a n S A E. 
•  U n k n o w n:  T his ter m is o nl y a p plica ble if t he s u bject is l ost t o f oll o w -u p.  
 
F oll o w -u p of A E a n d S A E  
T he i n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d u ct of s u p ple me ntal meas ure me nts 
a n d/ or e val uati o ns as me dicall y i n dicat e d or as re q ueste d b y N o v o N or dis k t o el uci date t he nat ur e 
a n d/ or ca us alit y of t he A E or S A E as f ull y as p ossi ble (e. g. , se vere h y perse nsiti vit y reacti o ns). 
T his ma y i ncl u de a d diti o nal la b orat or y tests ( e. g. , s ki n pric k test) or i n vesti gati o ns, 
hist o pat h ol o gical e x a mi nati o ns, or c o ns ultati o n wit h ot her healt h care pr ofessi o nals.  
N N 9 7 7 5- 4 7 0 8
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9 2
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
9 3  of 1 1 6  
 
If a s u bject die d uri n g partici pati o n i n t he trial or d uri n g a rec o g nise d f oll o w -u p peri o d, t he 
i n vesti gat or s h o ul d pr o vi de N o v o N or dis k wit h a c o p y of a ut o ps y re p ort i ncl u di n g hist o pat h ol o g y 
or certificate of d eat h.  
Ne w or u p d ate d i nf or mati o n will be rec or de d i n t he C R F.  
 
1 0. 3. 5  
Re p orti n g of S A Es  
S A E re p orti n g vi a electr o nic C R F  
•  Rele va nt f or ms ( A E a n d safet y i nf or mati o n f or m) m ust be c o m plete d i n t he C R F.   
•  F or re p orti n g a n d si g n -off ti meli nes, see Fi g ure  1 0 -1  bel o w.  
•   If t he C R F is u na vaila bl e f or m ore t h a n 2 4 h o urs, t he n t he site will use t he pa per A E f or m, 
a n d if t he C R F is u na vail a ble f or m ore t ha n 5 cale n dar da ys, t he n t he site will use t he safe t y 
i nf or mati o n f or m (see b o x bel o w). 
•  T he site will e nter t he S A E data i nt o t he C R F as s o o n as it bec o mes a vaila ble.  
•  After t he trial is c o m plet e d, t he trial data base will be l oc ke d, a n d t h e C R F will be 
dec o m missi o ne d t o pre ve nt t he e ntr y of ne w data or c ha n ges t o e xisti n g data. If a site recei v es 
a re p ort of a ne w S A E fr o m a s u bject or recei ves u p date d data o n a pre vi o usl y re p orte d S A E 
after C R F d ec o m missi o n, t he n t he site ca n re p ort t his i nf or mati o n o n a pa per A E a n d safet y 
i nf or mati o n f or m (see b o x bel o w) or t o N o v o N or dis k  b y tele p h o ne.  
 
A E a n d S A E re p orti n g vi a p a per C R F  
•  Rele va nt C R F f or ms ( A E a n d safet y i nf or mati o n f or m)  m ust be f or war de d t o N o v o N or dis k 
i n acc or da nce wit h Secti o n 1 0. 1. 5 . 
•  F or S A Es, i nitial n otificati o n via tele p h o ne is acce pta ble, alt h o u g h it d oes n ot re place t h e 
nee d f or t h e i n vesti gat or t o c o m plete t he A E a n d s afet y i nf or mati o n f or m  wit hi n t he 
desi g nat e d re p orti n g ti meli nes (as ill ustrate d i n t he fi g ure bel o w):  
•  A E f or m wit hi n 2 4 h o urs  
•  Safet y i nf or mati o n f or m wit hi n 5 cale n dar da ys  
•  B ot h f or ms m ust be si g n e d wit hi n 7 cale n dar da ys after first k n o wle d ge b y t he i n vesti gat or.  
•  T he s pecific e ve nt f or m f or A Es re q uiri n g a d diti o nal data c ollecti o n wit hi n 1 4 cale n dar da ys  
 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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1
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 of
  Pr ot oc ol  versi o n 4. 0
9 3
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
9 4  of 1 1 6  
 
Fi g ure  1 0 -1  Decisi o n tree f or deter mi ni n g t he e ve nt t y pe a n d t he res pecti ve f or ms t o 
c o m plete wit h ass oci ate d ti meli nes 
 
C o ntact details f or S A E re p orti n g ca n be f o u n d i n t he i n vesti gat or tri al master file.  
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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1
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 of
  Pr ot oc ol  versi o n 4. 0
9 4
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
9 5  of 1 1 6  
 
1 0. 4  A p pe n di x 4: C o ntr ace pti ve g ui d a nce a n d c ollecti o n of pre g n a nc y i nf or m ati o n  
Defi niti o ns  
W o m a n of c hil d be ari n g p ote nti al ( W O C B P)  
A w o ma n is c o nsi dere d fertile f oll o wi n g m e narc h e a n d u ntil bec o mi n g p ost me n o pa usal u nless 
per ma ne ntl y sterile.  If fertilit y is u ncle ar (e. g., a me n orr hea i n a d olesce nts or at hletes), a n d a 
me nstr ual c ycle ca n n ot b e c o nfir me d b ef ore first d ose of trial treat me nt, a d dit i o nal e val uati o n 
s h o ul d be c o nsi dere d. 
Fe m ales i n t he f oll o wi n g c ate g ori es are n ot c o nsi dere d W O C B P  
1.  Pre me narc heal  
2.  Fe males wit h o ne or m or e of t he f oll o wi n g:  
•  D oc u me nte d t otal h ysterect o m y  
•  D oc u me nte d bilateral sal pi n gect o m y  
•  D oc u me nte d bilateral o o p h orect o m y  
Fe males wit h per ma ne nt i nfertilit y d ue t o a n alter nate me dical ca use ot her t ha n t he a b o ve 
(e. g., M ülleria n a ge nesis, a n dr o ge n i nse nsiti vit y).  
3.  P ost me n o pa usal fe male:  
•  A p ost me n o pa usal state is defi ne d as a m e n orr h o ea f or 1 2 m o nt hs wit h o ut a n alter nati ve 
me dic al ca us e.  
•  Fe males  ≥ 5 0 years of a ge ca n b e c o nsi dere d p ost me n o pa usal (irres pecti ve of treat me nt 
wit h a 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)) if t he y h a ve 
b ot h:  
•  A me n orr h oea a n d  
•  D oc u me ntati o n of 2 hi g h F S H meas ure me nts i n t he p ost me n o pa usal ra n ge a n d o ne 
of t hese was o bs er ve d ≥1 year pri or t o s cree ni n g.  
•  Fe males ≥ 6 0 years of a ge ca n b e c o nsi dere d p ost me n o pa usal.  
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 are c o nsi dere d of c hil d beari n g p ote ntial 
a n d will be re q uir e d t o use o ne of t he hi g hl y effecti ve c o ntrace pti o n met h o ds.  
N ote: D oc u me ntati o n re gar di n g cate g ories 1 -3 ca n c o me fr o m t he site staff’s re vi e w of s u bject’s 
me dical rec or ds, me dic al e x a mi nati o n or me dical hist or y i nter vie w.  
C o ntr ace pti o n g ui d a nce  
Male s u bjects   
T he I M P cate g or y i s “ n o n-ge n ot o xic ” a n d t here are n o data t o s u p p ort e m br y o -f oetal cate g orisati o n 
( C T F G g ui deli ne). F or bi ol o gics, i ncl u di n g pr otei n/ pe pti des, tra nsfer of dr u g via se m e n t o a 
n o n -treate d fe male p art n er is ge nerall y c o nsi dere d t o be i nsi g nifica nt5 3. Bi ol o gics c o ntai ni n g 
u n nat ural a mi n o aci ds a n d/ or c he mical li n kers ca n be c o nsi dere d as pr otei ns/ pe pti des. T heref ore, 
t he are n o me as ures f or male s u bjects. 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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1
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 of
  Pr ot oc ol  versi o n 4. 0
9 5
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
9 6  of 1 1 6  
 
Fe male s u bjects  
Fe male s u bjects of c hil d beari n g p ote ntial are eli gi ble t o partici pate if t he y a gree t o us e hi g hl y 
effecti ve c o ntr ace pti ve m et h o ds, prefera bl y wit h l o w user de p e n de nc y as d escri be d i n t he ta bl e 
bel o w:  
T a ble  1 0 -3  
Hi g hl y effecti ve a n d acce pt a ble c o ntr ace pti ve met h o ds  
C O N T R A C E P TI V E S a, g A L L O W E D D U RI N G T H E T RI A L I N C L U D E:  
•  Hi g hl y effecti ve met h o ds b  t h at h a ve l o w user de pe n de nc y ( Fail ure rate of < 1 % per year 
w he n use d c o nsiste ntl y a n d c orrectl y):  
•  I m pla nta bl e pr o gest o ge n-o nl y h or m o n e c o ntrace pti o n ass o ciate d wit h i n hi biti o n of o v ulati o n  
•  I ntr a uteri ne d e vice (I U D) 
•  I ntr a uteri ne h or m o ne-rel easi n g s yst e m (I U S) 
•  Bilateral t u bal occl usi o n  
•  Vasect o mi se d part ner c ( T he t w o vas defere ns are tie d a n d se vere d. T h e e n ds ma y b e 
ca uteriz e d)  
•  Hi g hl y effecti ve met h o ds b  t h at are user de pe n d e nt ( Fail ure rate of < 1 % per year w he n us e d 
c o nsiste ntl y a n d c orrectl y):  
•  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 
•  
i njecta ble 
•  Se x ual a bsti ne nce  
•  Pr o gest o ge n o nl y 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 d 
•  oral  
•  i njecta ble. 
N O T E S  
a)  C o ntrace pti ve use b y me n or w o me n s h o ul d be c o nsiste nt wit h l ocal re g ul ati o ns re gar di n g t he 
use of c o ntrace pti ve met h o ds f or t h ose partici pa ti n g i n cli nical trials. 
b)  Fail ure rate of < 1 % p er year w h e n use d c o nsiste ntl y a n d c orrectl y. T y pical use fail ure rates 
differ fr o m t h ose w he n use d c o nsiste ntl y a n d c orrectl y.  
c)  Vasect o mi se d part ner is a hi g hl y effecti ve c o ntr ace pti ve met h o d pr o vi de d t hat t he part ner is 
t he s ole se x ual part ner of t he w o ma n of c hil d beari n g p ote ntial, a n d t h e a bse nce of s per m has 
bee n c o nfir me d. If n ot, a n a d diti o nal hi g hl y effecti ve met h o d of c o ntrace pti o n s h o ul d be use d. 
S per mat o ge nesis c ycl e is a p pr o xi matel y 9 0 da ys.  
d)  H or m o nal c o ntrace pti o n ma y b e s usce pti ble t o i nteracti o n wit h t he I M P, w hic h ma y re d uce 
t he effic ac y of t h e c o ntrace pti o n met h o d.  
e)  Se x ual a bsti ne nce is c o nsi dere d a hi g hl y effecti ve met h o d o nl y if defi ne d as refrai ni n g fr o m 
heter ose x ual i nterc o urs e d uri n g t he e ntire peri o d of ris k ass ociate d wit h t he trial treat me nt. 
T he relia bilit y of se x ual a bsti ne nce nee ds t o be e v al uate d i n relati o n t o t he d urati o n of t he trial 
a n d t he preferre d a n d us u al lif est yle of t he s u bject  
f) C o ntrace pti o n s h o ul d be utilise d d uri n g t he treat me nt peri o d a n d f or at least 6 0 da ys 
(c orres p o n di n g t o ti me n ee de d t o eli mi nate trial pr o d uct) aft er t he last d ose of trial pr o d uct. 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
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1
 |
 of
  Pr ot oc ol  versi o n 4. 0
9 6
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
9 7  of 1 1 6  
 
Pre g n a nc y testi n g  
•  W o me n/ W O C B P s h o ul d o nl y be i ncl u d e d after a n e gati ve hi g hl y s e nsiti ve uri ne pre g n a nc y test 
(refer t o A p pe n di x 2, Secti o n 1 0. 2 ). 
•  A d diti o nal  hi g hl y s e nsiti ve uri ne pre g na nc y t e sti n g f or W O C B P o nl y s h o ul d be perf or me d 
e ver y sec o n d wee k / f o urt h wee k d uri n g t he tr eat me nt peri o d, a n d at e n d of trial e n d of rele va nt 
s yste mic e x p os ure; pleas e refer t o t he fl o w c hart. 
•  Pre g n a nc y testi n g s h o ul d be perf or me d w he ne ver a me nstr uati o n is mi sse d or w he n pre g na nc y 
is ot her wise s us pecte d. 
C ollecti o n of pre g n a nc y i nf or m ati o n   
Fe m ale s u bjects w h o bec o me pre g n a nt   
•  I n v esti gat or will c ollect pre g na nc y i nf or mati o n o n a n y fe male s u bj ect w h o bec o mes pre g na nt 
w hile partici pati n g i n t his trial.  
•  I nf or matio 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 N o v o N or dis k wit hi n 
1 4  cale n dar da ys of lear ni n g of a s u bj ect ’s pre g na nc y. 
•  S u bject 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 s u bject a n d ne o n ate w hic h will be f or war de d t o N o v o N or dis k 
wit hi n 1 4 cale n dar da ys. Ge nerall y, f oll o w -u p will n ot be re q uire d f or l o n ger t ha n 1 m o nt h 
be y o n d t h e deli ver y d ate.  
•  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 f o etal stat us ( prese nce or a bs e 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 a d v erse e ve nt i n c o n necti o n 
wit h pre g na nc y or ele cti ve ter mi nati o n of a pre g na nc y f or me dical reas o ns will be re p orte d as a n 
A E  or S A E. If rele va nt, c o nsi der a d di n g ‘ gestati o n al’, ‘ pre g n a nc y relate d’ or a si milar ter m 
w he n re p orti n g t he A E/ S A E.  
•  Pre g n a nc y o utc o me s h o ul d be d oc u me nte d i n t he s u bject ’s me dical r ec or d. A b n or mal pre g n a nc y 
o utc o me (e. g. , s p o nta n e o us a b orti o n, f oetal deat h, still birt h, c o n ge nital a n o malies a n d ect o pic 
pre g na nc y) is c o nsi dere d a n S A E.  
•  A n y S A E o cc urri n g as a res ult of a p ost -trial pr e g na nc y w hic h is c o nsi dere d p ossi bl y/ pr o ba bl y 
relate d t o t he I M P b y t he i n vesti gat or will be re p orte d t o N o v o N or dis k as d escri be d i n 
A p pe n di x  3, Secti o n  1 0. 3 . W hile t he i n vesti gat or is n ot o bli gate d t o acti vel y see k t his 
i nf or mati o n i n f or mer s u bjects, he or s he ma y l ear n of a n S A E t hr o u g h s p o nta ne o us re p orti n g.  
A n y fe male s u bject w h o bec o mes pre g na nt w hile partici pati n g i n t he tri al will disc o nti n ue I M P.  
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
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1
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 of
  Pr ot oc ol  versi o n 4. 0
9 7
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
9 8  of 1 1 6  
 
1 0. 5  A p pe n di x 5: Tec h nic al c o m pl ai nts:  Defi niti o n a n d pr oce d ures f or rec or di n g, 
e v al u ati o n, f oll o w -u p a n d re p orti n g  
1 0. 5. 1  
Defi niti o n of tec h nic al c o m pl ai nt  
Tec h nic al c o m pl ai nt defi niti o n  
•  A tec h nical c o m plai nt  is a n y writte n, electr o nic or oral c o m m u nicati o n t hat alle ges pr o d uct 
( me dici ne or de vice) defects. T he tec h nical c o m pl ai nt ma y b e ass ociat e d wit h a n A E b ut d oes 
n ot c o ncer n t he A E itself.  
E x a m ples of tec h nical c o m plai nts:  
•  Pr o ble ms wit h t he p h ysic al or c he mical a p peara n ce of trial pr o d ucts ( e. g. , disc ol orati o n, 
particles or c o nt a mi nati o n)  
•  Pr o ble ms wit h pac ka gi n g material i ncl u di n g l a belli n g  
•  Pr o ble ms relate d t o de vices (e. g. , t o t he i njecti o n mec ha nis m, d ose setti n g mec ha nis m, p us h 
b utt o n or i nterface bet wee n t he pe n -i nject or a n d t h e nee dle) 
Ti me peri o d f or detecti n g tec h nic al c o m pl ai nts  
All tec h nical c o m plai nts w hic h occ ur fr o m t he ti me of recei pt of t he pr o d uct at site u ntil t he ti me 
of t he last usa ge of t h e pr o d uct m ust be c ollecte d f or pr o d ucts pre d efi ne d o n t he tec h nical 
c o m plai nt f or m.  
 
1 0. 5. 2  
Rec or di n g a n d f oll o w -u p of tec h nic al c o m pl ai nts  
Re p orti n g of tec h nic al c o m pl ai nts t o N o v o N o r dis k  
C o ntact details f or C ust o mer C o m plai nt Ce nter, please refer t o Attac h me nt I . 
Tec h nical c o m plai nts m ust be re p orte d o n a se parate tec h nical c o m plai nt f or m:  
1.  O ne tec h nic al c o m plai nt f or m m ust be c o m plete d f or e ac h affecte d D U N.  
2.  If D U N is n ot a v aila ble, a tec h nical c o m plai nt f or m f or eac h batc h, c o de or l ot n u m ber m ust 
be c o m plete d.  
 
Ti meli nes f or re p orti n g of tec h nic al c o m pl ai nts t o N o v o N or dis k  
T he i n vesti gat or m ust c o m plete t he tec h nical c o m plai nt f or m i n t he C R F wit hi n: 
•  2 4 h o urs if relate d t o a n S A E  
•  5 cale n dar da ys f or all ot her tec h nical c o m plai nts  
If t he C R F is u na vaila ble, or w he n re p orti n g a tec h nical c o m plai nt o n a trial pr o d uct t hat is n ot 
yet all ocate d t o s u bject, t he i nf or mati o n m ust be pr o vi de d o n a pa p er f or m t o C ust o mer 
C o m plai nt Ce nter, N o v o N or dis k, wit hi n t he sa me ti meli nes as state d a b o ve. W he n t he C R F 
bec o mes a v aila ble a gai n, t he i n vesti gat or m ust e nt er t he i nf or mati o n o n t he tec h nical c o m plai nt 
f or m i n t he C R F. 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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V V- T M F- 5 0 4 2 3 4 5
 .
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1
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 of
  Pr ot oc ol  versi o n 4. 0
9 8
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
9 9  of 1 1 6  
 
F oll o w -u p of tec h nic al c o m pl ai nts  
T he i n vesti gat or is res p o nsi ble f or e ns uri n g t hat n e w or u p date d i nf or mati o n will be rec or de d o n 
t he ori gi nall y c o m plet e d f or m. 
 
C ollecti o n, st or a ge a n d s hi p me nt of tec h nic al c o m pl ai nt s a m ples  
T he i n vesti gat or m ust c ollect t he tec h nical c o m plai nt sa m ple a n d all ass ociate d parts t hat were 
pac ke d i n t he sa m e D U N a n d n otif y t he m o nit or wit hi n 5 cale n dar da ys of o btai ni n g t he sa m ple at 
site. T he sa m ple a n d all ass ociate d parts m ust be s e nt as s o o n as p ossi ble t o C ust o mer  C o m plai nt 
Ce nter, N o v o N or dis k, t o get h er wit h a c o p y of t he c o m plete d tec h nical c o m plai nt f or m. T he 
tec h nical c o m plai nt sa m ple s h o ul d c o ntai n t he batc h, c o de or l ot n u m ber a n d, if a vaila ble, t he 
D U N. If t he t ec h nic al c o m plai nt sa m ple is u n o btai na ble, t he reas o n m ust be state d o n t he 
tec h nical c o m plai nt f or m. If se veral sa m ples are s hi p pe d i n o ne s hi p me nt, t he sa m ple a n d t he 
c orres p o n di n g te c h nical c o m plai nt f or m s h o ul d be ke pt t o get her.  
St ora ge of t he te c h nical c o m plai nt sa m ple m ust be d o ne i n acc or da nce w it h t he c o n diti o ns 
prescri be d f or t he pr o d uct.  
 
1 0. 5. 3  
Re p orti n g of tec h nic al c o m pl ai nts  
Re p orti n g of tec h nic al c o m pl ai nts f or N o v o N or dis k pr o d ucts n ot i ncl u de d i n tec h nic al 
c o m pl ai nt f or m  
Tec h nical c o m plai nts o n N o v o N or dis k pr o d ucts n ot i ncl u de d i n t he tec h n ical c o m plai nt f or m 
s h o ul d be re p orte d t o l ocal N o v o N or dis k. 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
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1
 |
 of
  Pr ot oc ol  versi o n 4. 0
9 9
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 0 0  of 1 1 6  
 
1 0. 6  A p pe n di x 6: Ge netics  
N ot a p plica ble i n t his trial. 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 0 1  of 1 1 6  
 
1 0. 7  A p pe n di x 7: Me dic al de vice a d verse e ve nts, a d v erse de vice effects, seri o us a d verse 
e ve nts a n d de vice deficie ncies: Defi niti o n a n d pr oce d ures f or rec or di n g, e v al u ati n g, 
f oll o w-u p, a n d re p orti n g  
1 0. 7. 1  
Defi niti o n of A E a n d a d verse de vice effects ( A D E)  
A E a n d A D E de fi niti o n  
•  A n A E is defi ne d as a n y u nt o war d me dical o cc urre nce, u ni nte n d e d disease or i nj ur y, or 
u nt o war d cli nical si g ns (i ncl u di n g a b n or mal la b orat or y fi n di n g) i n trial s u bjects, users, or 
ot her pers o ns, w h et her or n ot relate d t o t he i n vesti gati o nal me di cal de vice. T his defi niti o n 
i ncl u des e ve nts rel ate d t o t he i n vesti gati o nal me di cal de vice or c o m parat or a n d e ve nts r elate d 
t o t he pr oce d ures i n v ol ve d, e x ce pt f or e ve nts i n us ers or ot her p ers o ns w hic h o nl y i ncl u de 
e ve nts relat e d t o i n vesti gati o nal me di cal de vices.  
•  A n A D E is defi ne d as a n A E relate d t o t he us e of a n i n vesti gati o nal me dical de vice. T his 
defi niti o n i ncl u des a n y A Es res ulti n g fr o m i ns ufficie nt or i na de q u ate i nstr ucti o ns f or use, 
de pl o y me nt, i m pla ntati o n, i nstallati o n, or o perati o n, or a n y m alf u ncti o n of t he i n vesti gati o nal 
me dical de vice as well as a n y e ve nt r es ulti n g fr o m use err or or fr o m i nte nti o nal mis use of t he 
i n vesti gati o nal me dic al de vice. 
 
1 0. 7. 2  
Defi niti o n of S A E, seri o us a d verse de vice effect ( S A D E) a n d u ne xce pte d seri o us 
a d verse de vice  effect ( U S A D E)  
A n S A E is a n A E t h at:  
a. Le d t o d eat h  
b.  Le d t o s eri o us deteri orati o n i n t he healt h of t he s u bject t hat eit her res ulte d i n:  
1.  A life -t hreate ni n g ill ness or i nj ur y. T h e ter m ‘lif e-t hreate ni n g’ i n t he d efi niti o n of ‘seri o us’ 
refers t o a n e v e nt i n w hic h t he s u bject was at ris k of deat h at t he ti me of t h e e ve nt. It d oes n ot 
refer t o a n e v e nt w hic h h y p ot heticall y mi g ht ha ve ca use d deat h, if it were m ore se vere. 
2.  A per ma ne nt i m pair m e nt of a b o d y str uct ur e or a b o d y f u ncti o n.  
3.  I n p atie nt or pr ol o n ge d h os pitalisati o n pla n ne d h os pitali sati o n f or a pre-e xisti n g c o n diti o n, or a 
pr oce d ure re q uire d b y t h e pr ot oc ol, wit h o ut seri o us deteri orati o n i n healt h, is n ot c o nsi dere d 
a n S A E. 
4.  Me dical or s ur gic al i nter ve nti o n t o pre ve nt life -t hreate ni n g ill ness or i nj ur y or per ma n e nt 
i m pair me nt t o a b o d y str uct ure or a b o d y f u ncti o n. 
c. Le d t o f o etal distress, f o etal deat h or a c o n ge nital a b n or malit y or birt h defect  
S A D E defi niti o n  
•  A S A D E is defi ne d as a n a d verse d e vice effect t hat has res ulte d  i n a n y of t h e c o nse q ue n ces 
c haracteristic of a S A E.  
U S A D E defi niti o n  
•  A U S A D E is a seri o us a d verse de vi ce effect w hic h b y its nat ure, i n ci de nce, se verit y or 
o utc o me has n ot bee n i de ntifie d i n t he c urre nt ris k assess me nt a nal ysis re p ort (see 
Secti o n  2. 3 ). 
•  A ntici pate d seri o us a d v erse de vice effect ( A S A D E) is a n effect w hic h b y its nat ure, 
i nci de nce, se v erit y or o ut c o me has bee n i de ntifie d i n t he ris k assess me nt. 
N N 9 7 7 5- 4 7 0 8
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 0 2  of 1 1 6  
 
1 0. 7. 3  
Defi niti o n of de vice deficie nc y  
De vice deficie nc y defi niti o n  
•  A de vice d eficie n c y is a n i na de q uac y of a me dical de vice wit h res p ect t o its i de ntit y, q ualit y, 
d ura bilit y, relia bilit y, safet y, or perf or ma nce. De vice defici e ncies i ncl u de malf u ncti o ns, use 
err ors, a n d i na de q u ate la belli n g. De vi ce deficie nc y is part of tec h nical c o m plai nt defi niti o n, 
please refer t o A p pe n di x 5 , Secti o n 1 0. 5 . 
 
1 0. 7. 4  
Rec or di n g a n d f oll o w -u p of A E a n d/ or S A E a n d de vice deficie ncies  
A E, S A E a n d de vice deficie nc y rec or di n g  
•  W he n a n A E/ S A E/ de vice deficie nc y o cc urs, it is t he res p o nsi bilit y of t he i n vesti gat or t o 
re vie w all d oc u m e ntati o n (e. g., h os pital pr o gress n otes, la b orat or y re p orts, a n d dia g n ostics 
re p orts) relate d t o t he e v e nt. 
•  T he i n vesti gat or will t he n rec or d all rele va nt A E/ S A E/ de vice defi cie nc y i nf or mati o n i n t he 
s u bject’s me dical r ec or ds, i n acc or da nce wit h t he i n vesti gat or’s n or mal cli nical practice a n d 
o n t he a p pr o priat e f or m of t he C R F.  
•  F or de vic e deficie ncies, it is ver y i m p orta nt t hat t h e i n vesti gat or descri bes a n y c orrecti ve 
acti o ns ta ke n t o pre v e nt r ec urre nce of t he e v e nt.  
Assess me nt of i nte nsit y  
T he i n vesti gat or will ma ke a n  assess me nt of i nte nsit y f or eac h A E/ S A E re p orte d d uri n g t he trial 
a n d assi g n it t o o ne of t h e f oll o wi n g cate g ories:   
•  Mil d: A n e ve nt t hat is easil y t olerate d b y t h e s u bject, ca usi n g mi ni mal disc o mf ort a n d n ot 
i nterferi n g wit h e v er y da y acti vities. 
•  M o derate:  A n e ve nt t hat ca uses s ufficie nt disc o mf ort a n d i nterferes wit h n or mal e ver y d a y 
acti vities. 
•  Se vere: A n e v e nt t hat pre ve nts n or mal e ver y d a y acti vities. A n A E t hat is assesse d as se vere 
s h o ul d n ot be c o nf use d wit h a S A E. Se vere is a cat e g or y utilize d f or rat i n g t he i nte nsit y of a n 
e ve nt; a n d b ot h A Es a n d S A Es ca n be ass esse d as se vere.  
A n e ve nt is defi ne d as ‘s eri o us’ w he n it meets at least 1 of t he pre defi n e d o utc o mes as descri be d 
i n t he defi niti o n of a n S A E, N O T w he n it is rate d as se vere. 
 
Assess me nt of c a us alit y  
•  T he i n vesti gat or is o bli gate d t o assess t he relati o ns hi p bet wee n trial pr o d u ct a n d eac h 
occ urre nce of eac h A E/ S A E  
•  A “reas o na ble p ossi bilit y” of a relati o ns hi p c o n ve ys t hat t here are facts, e vi de nce, a n d/ or 
ar g u me nts t o s u g gest a ca usal relati o ns hi p, rat h er t ha n a relati o ns hi p ca n n ot be r ule d o ut.  
•  T he i n vesti gat or will use cli nical j u d g me nt t o deter mi ne t he relati o ns hi p.  
•  Alter nati ve ca uses, s uc h as u n derl yi n g disease(s), c o nc o mita nt t hera p y, a n d ot her ris k fact ors, 
as well as t he te m p or al relati o n s hi p of t he e ve nt t o trial pr o d uct a d mi nistrati o n, will be 
c o nsi dere d a n d i n vesti gate d.  
•  T he i n vesti gat or will als o c o ns ult t he In v esti gat or’s B r oc h ure a n d, f or mar kete d pr o d ucts, i n 
his/ her assess me nt.  
N N 9 7 7 5- 4 7 0 8
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Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 0 3  of 1 1 6  
 
•  F or eac h A E/ S A E, t he i n vesti gat or m ust  d oc u me nt i n t he  me dical rec or ds t hat he/s he has 
re vie we d t h e A E/ S A E a n d has pr o vi de d a n assess me nt of ca usalit y f or A E or S A E. 
•  T here ma y b e sit uati o ns i n w hic h a n A E/ S A E has occ urre d, a n d t he i n v esti gat or h as mi ni mal 
i nf or mati o n t o i ncl u de i n t he i nitial re p ort t o N o v o Nor dis k. H o we ver, it is ver y i m p orta nt t hat 
t he i n vesti gat or al wa ys ma kes a n assess m e nt of ca usalit y f or e ver y e v e nt bef ore t h e i nitial 
tra ns missi o n of t he S A E data. 
•  T he i n vesti gat or ma y c h a n ge his/ her o pi ni o n of ca usalit y i n li g ht of f oll o w -u p i nf or mati o n 
a n d se n d a n A E/ S A E f oll o w -u p re p ort wit h t he u p date d ca us alit y ass ess me nt.  
•  T he ca us alit y ass ess me nt is o ne of t he criteria use d w he n deter mi ni n g re g ulat or y re p orti n g 
re q uire me nts. 
 
F oll o w -u p of A E/ S A E/ de vice deficie nc y  
•  T he i n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d u ct of s u p ple me ntal 
meas ure me nts a n d/ or e val uati o ns as me dicall y i n dicate d or as re q uest e d b y N o v o N or dis k t o 
el uci date t he nat ure a n d/ or ca usalit y of t he A E/ S A E/ de vice deficie nc y as f ull y as p ossi ble. 
T his ma y i ncl u de a d diti o nal la b orat or y tests or i n v esti gati o ns, hist o pat h ol o gical e xa mi nati o ns, 
or c o ns ultati o n wit h ot her healt h care pr ofessi o nals.  
•  Ne w or u p d ate d i nf or mati o n will be rec or de d i n t he ori gi n all y c o m plete d C R F.  
•  T he i n vesti gat or will s u b mit a n y u p date d S A E d ata t o  N o v o N or dis k wit hi n 2 4 h o urs of 
recei pt of t h e i nf or mati o n. 
 
1 0. 7. 5  
Re p orti n g of S A Es  
S A E re p orti n g t o N o v o N or dis k vi a p a per C R F  
•  Rele va nt C R F f or ms ( A E a n d safet y i nf or mati o n f or m)  m ust be f or war de d t o N o v o N or dis k 
i n acc or da nce wit h Secti o n 1 0. 1. 5 . 
•  I nitial n otificati o n via tel e p h o ne is acce pta ble, alt h o u g h it d oes n ot re pl ace t he nee d f or t he 
i n vesti gat or t o c o m plete t he A E a n d safet y i nf or m ati o n f or m wit hi n t he desi g nate d re p orti n g 
ti me fra mes: 
•  A E f or m wit hi n 2 4 h o urs  
•  Safet y i nf or mati o n f or m wit hi n 5 cale n dar da ys   
•  B ot h f or ms m ust be si g n e d wit hi n 7 cale n dar da ys after first k n o wle d ge b y t he i n vesti gat or.  
 
1 0. 7. 6  
Re p orti n g of de vice deficie ncies  
Re p orti n g t o N o v o N or dis k  
N O T E: T here are a d diti o nal re p orti n g o bli gati o ns t o n otif y a p pr o priate re g ulat or y a ut h orities a n d 
ot her e ntities a b o ut certai n safet y i nf or mati o n f or de vice deficie nci es t hat c o ul d ha ve le d t o S A Es. 
T he i n vesti gat or m ust t heref ore i n dicate i n t he tec h nical  c o m plai nt f or m if a tec h nical c o m plai nt 
( de vice d eficie n c y) c o ul d ha ve le d t o a n S A E. F or re p orti n g ti meli nes, pleas e refer t o A p pe n di x  5 , 
Secti o n  1 0. 5 . 
 
N N 9 7 7 5- 4 7 0 8
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 0 4  of 1 1 6  
 
1 0. 8  A p pe n di x 8: Rete nti o n of h u m a n bi os a m ples  
H u ma n bi osa m ples (als o i n s o me cases k n o w n as h u ma n bi os peci me n or h u ma n bi ol o gical 
materials) are sa m ples t h at ha ve bee n ta ke n fr o m t he h u ma n b o d y d uri n g life or aft er deat h. It 
i ncl u des:  
•  Pri mar y cells, tiss ues, or ga ns or cell c o nt ai ni n g fl ui ds of h u ma n ori gi n ( e. g., w h ole bl o o d, uri ne, 
sali va, s y n o vial fl ui d)  
•  Cell -free fl ui ds of pri mar y h u ma n ori gi n (e. g., ser u m a n d plas ma)  
•  E xtracts or deri vati ves of t he a b o ve, w he n deri ve d b y p urifi cati o n ( e. g., D N A, R N A, pr otei ns, 
me m bra nes, micr os o mes a n d ot her cell ular s u bstr uct ures). I n c o u ntries w h ere a p plica ble, t he 
trial will i n v ol ve c ollecti o n of h u ma n bi osa m ples f or f ut ure e x pl orat or y a n al yses d uri n g or after 
t he trial, t o be st ore d i n a ce ntral la b orat or y facilit y. 
T he m ateri al t o be c ollecte d f or P a rt 1   
at baseli ne ( V 2)  
•  W h ole bl o o d (f or ge netic a nal ysis)  
•  Ser u m a n d plas ma (f or a nal ysis of circ ulati n g bi o mar kers)  
at V 1 5 
•  Ser u m a n d plas ma (f or a nal ysis of circ ulati n g bi o mar kers)  
T he m ateri al t o be c ollecte d f or P a rt 2  
at baseli ne ( V 2)  
•  w h ole bl o o d (f or ge netic a n al ysis)  
•  Ser u m a n d plas ma (f or a nal ysis of circ ulati n g bi o mar kers)  
at V 1 0, V 1 4, V 1 4c a n d V 1 8 
•  Ser u m a n d plas ma (f or a nal yses of cir c ulati n g bi o mar kers)  
F or ser u m sa m ples c ollecte d ( 8 m L w h ole bl o o d p er sa m ples) 5 ali q u ots will be st ore d  
F or plas ma s a m ples c o llecte d ( 8 m L w h ole bl o o d per sa m ples) 5 ali q u ots will be st ore d 
F or D N A sa m ples c ollecte d ( 8. 5 m L w h ole bl o o d per sa m ple) 1 ali q u ot will be st ore d.  
Sa m ples will be a n o n y mise d ( mar ke d a n d i de ntifie d o nl y b y a u ni q ue s a m ple I D, visit n u m ber a n d 
sa m pli n g date). C o nfi de ntialit y a n d pers o nal data pr otecti o n will be e ns ure d d uri n g st or a ge after t he 
e n d of trial a n d n o direct i de ntificati o n of t he patie nt will be st ore d t o get h er wit h t he sa m ples.  
P ote ntial f urt her a nal ys es of t he sa m ples will n ot ha ve a n y c o nse q u e n ces f or s u bject a n d t heir 
relati ves.  
T he bi osa m ples will be st ore d at a ce ntr al la b orat or y, at a ce ntral st ora ge facilit y or a n a nal ysi n g 
la b orat or y c o ntr acte d b y N o v o N or dis k f or u p t o 1 5 years after t he tri al has re p orte d . O nl y rele va nt 
N o v o  N or dis k, c o ns ulta nts, a u dit ors, researc h or ga nisati o ns or la b orat ories w or ki n g f or 
N o v o  N or dis k as well as st ora ge facilit y e m pl o yees will be a ble t o access t he st ore d bi osa m ples a n d 
ass ociate d dat a.  
N N 9 7 7 5- 4 7 0 8
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C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 0 5  of 1 1 6  
 
T he bi osa m ples ma y be tra nsferre d t o ot her c o u ntries f or a nal ysis  a n d will be destr o ye d at t he latest 
1 5 years after t he tri al has re p orte d . 
T he a nal yses of t he bi osa m ples f or f ut ure researc h are n ot i nte n de d t o i de ntif y s u bject s pecific 
fi n di n gs, b ut t o u n dersta n d a n d pre dict res p o nse t o se ma gl uti de a n d N N C 0 1 6 5-1 8 7 5 or  o besit y a n d 
relate d c o n diti o ns o n a p o p ulati o n le vel. 
A nal ys es will be d o ne o n t he bi osa m ples a n d ass o ciate d data ( data relati n g t o t he test res ults or 
res ults fr o m t he mai n st u d y). 
N o v o N or dis k will e ns ur e t hat t hir d part y c olla b orat ors li ve u p t o re g ulati o ns o n data pr otecti o n 
T he s u bject ma y re q uest t he st ore d bi osa m ples f or f ut ure res earc h t o be destr o ye d b y wit h dra wi n g 
t he desi g n ate d i nf or me d c o nse nt at a n y ti me p oi nt d uri n g or after t he trial. 
A nti b o d y s a m ples  
Resi d ual a nti b o d y sa m pl es ma y b e r etai ne d f or lat er a nal ys es f or f urt her c h aract erisati o n of 
a nti b o d y res p o nses t o war ds dr u g, if re q uir e d b y healt h a ut h orities or f or safet y reas o ns. Resi d ual 
a nti b o d y sa m ples ma y als o be use d f or assa y de v el o p me nt or vali dati o n p ur p oses, if nee d e d. 
Selecte d sa m ples w o ul d be p o ole d, a n d n ot be tracea ble t o a n y i n di vi d ual. P o oli n g w o ul d n ot be 
d o ne if it pre ve nte d rete nti o n of s ufficie nt sa m ple material f or p ossi ble f urt her c haracterisati o n of 
a nti b o d y res p o nses i n t his trial.  
F or sa m ples t hat ha v e alr ea d y be e n a nal yse d t h e res ults will n ot be re m o ve d fr o m t he datafile.  
 
N N 9 7 7 5- 4 7 0 8
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Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 0 6  of 1 1 6  
 
1 0. 9  A p pe n di x 9: Miti g ati o ns t o e ns ure s u bject s afet y a n d d at a i nte grit y d uri n g 
e pi de mics/ p a n de mics (e. g. C O VI D -1 9)  
I n case l o cal restri cti o ns d ue t o a n e pi de mic/ pa n d e mic lea ds t o l oc k-d o w n of a site, t he site m ust 
c o ntact t he S p o ns or ( N o v o N or dis k) t o all o w f or i m ple me ntati o n of t he miti gati o ns me nti o ne d i n 
t his A p pe n di x 9, Secti o n 1 0. 9  base d o n m ut ual a gree me nt.  
•  T he assess me nts liste d i n Ta ble  1 0 -4  i n dicat es t he mi ni m u m re q uire me nts t hat s h o ul d be 
perf or me d d uri n g a l oc k -d o w n, b ut sites s h o ul d al wa ys ma ke a n eff ort  t o perf or m all t he 
assess me nts as o utli ne d i n  Secti o n  1. 2 . I m ple me nt ati o n of s pecific miti gati o ns s h o ul d be base d 
o n assess me nt of feasi bilit y at t he i n di vi d ual site.  
•  If l ocal r e g ulati o ns, re q uire me nts a n d/ or g ui deli nes have bee n iss u e d, t hese m ust be c o m plie d 
wit h.  
1 0. 9. 1  
Visits  
•  Scree ni n g ( Visit 1) a n d ra n d o misati o n ( Visit 2 i n P art 1 a n d Visit 1 0 i n P art 2) s h o ul d al wa ys be 
perf or me d as p h ysical o n -site visits. If a site is u na ble t o perf or m t hese visits o n-site, scree ni n g 
a n d ra n d o misati o n of ne w s u bjects at t hat site s h o ul d be o n h ol d u ntil o n -site visits are p ossi ble. 
•  F or P art 1 all visits s h o ul d be perf or me d as p h ysic al o n -site visits, if i n a n y wa y p ossi ble 
•  F or P art 2 Visit 1 2, 1 4, 1 4 c, 1 6, 1 8 a n d 1 9 s h o ul d be perf or me d as p h ysic al o n -site visits, if i n 
a n y wa y p ossi ble.  
o  If cli nic o n-site visits are n ot p ossi ble, visits ca n be re place d b y p h o ne calls a n d 
assess me nts ca n b e c o n d ucte d re m otel y ( pl ease refer t o Secti o n  1 0. 9. 2 )  
•  If d ue t o tra v el restricti o ns or l oc k d o w n it is n ot p ossi ble f or t he s u bject t o c o me t o t he o n-site 
visits at t he cli nic t o ha ve bl o o d sa m ples dra w n, pr ocesses w ill be i m ple me nte d t o all o w f or 
bl o o d sa m ple c ollecti o n off -site e. g. at t he ge neral practiti o ner or at t he s u bjects h o me, if at all 
p ossi ble.  
•   If a site is cl ose d or if t h e site staff is n ot all o we d at site 
o  site m ust e ns ure t hat s u bjects ca n still re p ort A Es  
o  site m ust e ns ure t o li mit t he bac k-l o g i n E D C c o m pleti o n f or c o m plete d visits 
•  It is i m p orta nt t hat sites sta y i n cl ose c o ntact wit h t he s u bjects t o kee p o n m oti vati n g t he m 
 
1 0. 9. 2  
Assess me nts  
•  L ocal la b orat ories or dia g n ostic facilities ca n be use d f or hae mat ol o g y, bi o c he mistr y a n d E C G 
at t he i n vesti gat or’s discreti o n if o n -site visits are n ot p ossi ble or i n case of te m p orar y l oc k d o w n 
of t he ce ntr al la b orat or y. O nl y fi n di n gs meeti n g t h e defi niti o n f or a n A E ( pl ease refer t o 
A p pe n di x 3, Secti o n 1 0. 3 ) s h o ul d be re p ort e d i n t he e C R F. 
•  H o me meas ur e me nts of b o d y w ei g ht ( usi n g t he s u bjects o w n scale) a n d vital si g ns ca n b e 
perf or me d if o n -site visits are n ot p ossi ble a n d if d ee me d feasi ble f or t he s u bject. O nl y fi n di n gs 
meeti n g t he d efi niti o n f or a n A E (please refer t o A p pe n di x 3 , Secti o n 1 0. 3 ) s h o ul d be re p ort e d 
i n t he e C R F. 
•  Alter nati ve wa ys of c ollecti n g b o d y wei g ht e. g. at l o b b y area or o utsi de t he cli nic usi n g a 
‘ m o bile’ cali brat e d scales a p pr oac h ca n b e i ntr o d uce d  
•  C S S R S i nter vie w a n d P H Q -9 q uesti o n nair e ca n be c o m plete d o n t he p h o ne t o e ns ure s u bject 
safet y 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
1 0 6
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 0 7  of 1 1 6  
 
•  Sites m ust e ns ure t hat pre g n a nc y testi n g is perf or me d acc or di n g t o pr ot oc ol als o f or p h o ne 
visits, if p ossi ble  
If t he assess me nts i n dicat e d i n Ta ble  1 0 -4  ca n n ot be perf or me d as o n -site visits, usi n g re m ote 
assess me nts or at G P/a l o cal la b orat or y or dia g n ostic facilit y, t he y s h o ul d b e perf or me d at t he first 
p ossi ble ti me p oi nt f oll o wi n g t he ori gi nall y sc h e d ule d visit.  
1 0. 9. 3  
Tri al pr o d uct  
1 0. 9. 3. 1  
Alter n ati ve dis pe nsi n g met h o ds  
Alter nati ve dis pe nsi n g met h o ds of st u d y i nter ve nti o n ma y b e  i m ple me nte d, a n d details will be 
c o m m u nicate d a n d d o c u me nte d. T he dis pe nsi n g o pti o ns will be base d o n o pti o ns a n d re q uire me nts 
at c o u ntr y le vel a n d if per mitte d b y l ocal re g ulati o ns a n d N o v o N or dis k.  
1 0. 9. 4  
Mi ni m u m assess me nts f or P a rt 2 t o b e perf or me d d uri n g  l oc k d o w n 
T a ble  1 0 -4  
Mi ni m u m assess me nts f or P a rt 2 t o b e perf or me d d uri n g l oc k d o w n  
 
Pr ot o c ol 
secti o n 
Ra n d o mi -
sati o n 
P Y Y  d ose 
escalati o n  
P Y Y mai nte na nce  
E n d 
of 
Treat -
me nt  
E n d of 
Trial  
 Visit  
 
V 1 0  
V 1 2  
V 1 4  
V 1 4 c 
V 1 6  
V 1 8  
V 1 9  
 Ti mi n g of Visit Wee ks ( W)  
 
3 2  
3 6  
4 2  
4 4  
4 6  
4 8  
5 6  
 Visit Wi n d o w ( Da ys)  
 
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
0/ 5  
    Atte n d Visit Fasti n g  
5. 3. 1  
X  
 
X  
X  
 
X  
X  
    Ra n d o misati o n Criteria a n d          
Ra n d o misati o n  
7. 1  
X  
 
 
 
 
 
 
    Disc o nti n uati o n Criteria  
7. 1  
X  
X  
X  
X  
X  
 
 
    C o nc o mita nt Me dicati o n  
6. 5  
X  
X  
X  
X  
X  
X  
X  
    Hi g hl y se nsiti ve uri n e p re g na nc y Testb 
1 0. 4  
X  
X  
X  
X  
X  
X  
X  
    B o d y Meas ure me nts  
8. 1. 1  
X  
X  
X  
X  
X  
X  
X  
    P h ysical E x a mi n ati o n  
8. 2. 2  
X  
 
 
 
 
X  
 
    A d verse E ve nt  
8. 3 ,1 0. 3  
X  
X  
X  
X  
X  
X  
X  
    A E Re q uiri n g A d diti o nal Data  
1 0. 3. 3  
 
 
 
 
 
 
 
       Ac ute Ki d ne y I nj ur y  
1 0. 3. 3  
X  
X  
X  
X  
X  
X  
X  
       Ac ute Gall bla d der Disease  
1 0. 3. 3  
X  
X  
X  
X  
X  
X  
X  
       Ac ute P a ncreatitis  
1 0. 3. 3  
X  
X  
X  
X  
X  
X  
X  
       He patic E ve nt  
1 0. 3. 3  
X  
X  
X  
X  
X  
X  
X  
       Mali g na nt Ne o plas m  
1 0. 3. 3  
X  
X  
X  
X  
X  
X  
X  
    Me dicati o n Err or, Mis use a n d A b use  
1 0. 3. 3  
X  
X  
X  
X  
X  
X  
X  
    I njecti o n Site Reacti o n 
1 0. 3. 3  
X  
X  
X  
X  
X  
X  
X  
    Tec h nical C o m plai nt  
1 0. 5  
X  
X  
X  
X  
X  
X  
X  
    La b orat or y Assess me nts  
1 0. 2  
 
 
 
 
 
 
 
       Bi o c he mistr y  
1 0. 2  
X  
X  
X  
X  
X  
X  
X  
       A nti b o dies d  
1 0. 2  
X  
X  
X  
X  
X  
X  
X  
       Bi o mar kers  
1 0. 2  
X f g 
 
X f g 
X f g 
 
X f g 
X f g 
       C oa g ulati o n P ara meter  
1 0. 2  
X  
X  
X  
X  
X  
X  
X  
       Gl u c ose Meta b olis m  
1 0. 2  
X  
 
X  
X  
 
X  
X  
       Hae mat ol o g y  
1 0. 2  
X  
X  
X  
X  
X  
X  
X  
       H or m o nes  
1 0. 2  
X  
X  
X  
X  
 
X  
X  
       Li pi ds  
1 0. 2  
X  
 
X  
X  
 
X  
X  
       Uri nal ysis  
1 0. 2  
X  
X  
X  
X  
X  
X  
X  
       2 4 -h o ur uri ne  
1 0. 2  
X  
 
 
 
 
X  
 
P K  
8. 5 ,8. 6  
 
 
 
 
 
 
 
       Se ma gl uti de plas ma  
 
X  
 
X  
X  
 
X  
X  
       N N C 0 1 6 5 -1 8 7 5 plas ma  
 
 
X  
X  
X  
X  
X  
X  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
1 0 7
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 0 8  of 1 1 6  
 
 
Pr ot o c ol 
secti o n 
Ra n d o mi -
sati o n 
P Y Y  d ose 
escalati o n  
P Y Y mai nte na nce  
E n d 
of 
Treat -
me nt  
E n d of 
Trial  
 Visit  
 
V 1 0  
V 1 2  
V 1 4  
V 1 4 c 
V 1 6  
V 1 8  
V 1 9  
 Ti mi n g of Visit Wee ks ( W)  
 
3 2  
3 6  
4 2  
4 4  
4 6  
4 8  
5 6  
 Visit Wi n d o w ( Da ys)  
 
± 3  
± 3  
± 3  
± 3  
± 3  
± 3  
0/ 5  
    E C G  
8. 2. 4  
X  
 
X  
X  
 
X  
 
    Vital Si g ns  
8. 2. 3  
X  
X  
X  
X  
X  
X  
X  
    Cli nical O utc o me Ass ess me nts  
8. 2. 1  
 
 
 
 
 
 
 
       C -S S R S Si nce Last Visit  
8. 2. 1  
X  
 
X  
X  
 
X  
 
       P atie nt Healt h Q uesti o n naire –  9  
       ( P H Q-9)  
8. 2. 1  
X  
 
X  
X  
 
X  
 
    Bi osa m ples f or F ut ure A nal ysis h  
8. 2. 1  
X  
 
X  
X  
 
X  
 
    I W R S Sessi o n 
6  
X  
X  
X  
X  
 
 
X  
    Treat me nt C o m plia nce  
6. 4  
X  
X  
X  
X  
X  
 
 
    Dr u g Dis pe nsi n g  
 
X  
X  
X  
X  
X  
X  
 
    Ha n d O ut D ose Re mi n der Car d  
8  
X  
X  
X  
X  
 
 
 
    Ha n d O ut a n d I nstr uct i n Diar y  
8  
X  
X  
X  
X  
 
 
 
    C ollect, Re vie w a n d Tra nscri b e Diaries  
 
X  
X  
X  
X  
 
X  
 
    I nf or mati o n a b o ut Uri ne c ollecti o n a n d 
dis pe nsi n g of uri n e c o ntai ner  
8. 2. 5. 1  
 
 
 
 
X  
 
 
    Trai ni n g i n De vices  
6. 1. 1. 1  
X  
X  
X  
X  
X  
 
 
b F or fe male s u bj ects of c hil d b eari n g p ote ntial  
d A nti b o d y sa m ples m ust b e ta ke n pre -d ose.  
f Pr ostate S pecific A nti ge n i n s er u m - o nl y male s u bj ects  
g Le pti n a n d S ol u ble Le pti n R ece pt or  
h Ser u m a n d plas ma sa m ples will b e c ollecte d at all t he mar ke d visits  
 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
1 0 8
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 0 9  of 1 1 6  
 
1 0. 1 0  A p pe n di x 1 0 : A b bre vi ati o ns 
A D E  
a d verse de vice effect  
A E  
a d verse e ve nt  
A L T  
ala ni ne a mi n otra nsferase  
A S A D E  
a ntici pate d seri o us a d verse de vice effect  
A S T  
as partate a mi n otra nsferase  
B MI  
B o d y mass i n de x  
C R F  
case re p ort f or m  
C R O  
c o ntract researc h or ga nisati o n  
C T R  
cli nical trial re p ort  
D F U  
directi o ns f or use  
D N A  
de o x yri b o n ucleic aci d  
D U N  
dis pe nsi n g u nit n u m ber  
E A C  
e ve nt a dj u dicati o n c o m mittee  
E C G  
electr ocar di o gra 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  
F A S  
f ull a nal ysis set 
F D A A A  
F D A A me n d me nts Act  
F P G  
fasti n g plas ma gl uc 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  
H b A 1c  
gl ycate d hae m o gl o bi n  
H R T  
h or m o ne re place me nt t hera p y  
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 p e n de nt et hics c o m mittee 
I M P 
i n vesti 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 W R S 
i nteracti ve we b res p o nse s yste m  
L P L V  
last patie nt last visit  
L D L  
l o w-de nsit y li p o pr otei n  
P C D  
pri mar y c o m pleti o n date  
P G  
plas ma gl uc ose  
P H Q -9  
P atie nt Healt h Q uesti o n naire -9  
P L B  
Place b o  
P Y Y  
pe pti de Y Y  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
1 0 9
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 1 0  of 1 1 6  
 
P S A  
Pr ostate s pecific a nti ge n  
R N A  
ri b o n ucleic aci d 
S A D E  
seri o us a d verse de vice effect  
S A E  
seri o us a d verse e ve nt 
S A P  
statistical a nal ysis pla n 
s.c. 
s u bc uta ne o us 
S U S A R  
s us pecte d u ne x pecte d seri o us a d verse reacti o n  
T 2 D  
t y pe 2 dia betes 
T M M  
trial materials ma n ual 
U N L  
U p per n or mal li mit  
U S A D E  
U na ntici pate d seri o us a d verse de vice effect  
W O C B P  
w o ma n of c hil d beari n g p ote ntial  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
1 1 0
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 1 1  of 1 1 6  
 
1 0. 1 1  A p pe n di x 1 1: Pr ot oc ol a me n d me nt hist or y  
T he p r ot oc ol a me n d m e nt s u m mar y of c ha n ges ta ble f or t he c urre nt pr ot o c ol versi o n is l ocate d 
directl y b ef ore t he ta ble of c o nte nts.  
Pr ot oc ol ve rsi o n 3. 0 ( 0 3 N o ve m ber 2 0 2 1) , U S A 
O ver all r ati o n ale f or pre p ari n g pr ot oc ol, versi o n 3. 0:  
T he o verall rati o nale f or t he c ha n ges i m ple me nte d i n t he a me n de d pr ot oc ol is d ue t o a n a m bi g uit y 
i n t he te xt o utli ne d i n t he pr ot oc ol re gar di n g us e of ser um or hi g hl y se nsiti ve uri ne pre g na nc y t est. 
Si nce t he trial will o nl y use hi g hl y se nsiti ve uri ne pre g na nc y t ests a n d t he s e nsiti vit y b et wee n t h e 
t w o tests is c o nsi dere d e q uall y g o o d, t he te xt re gar di n g use of ser u m pre g na nc y t est has bee n 
re m o ve d fr o m t he pr ot oc ol.  
I n a d diti o n, p h ysic al e x a mi nati o n of  t he ge nit o-uri nar y s yste m is n ot re gar de d as i n dicate d f or b ot h 
fe male a n d m ale  s u bjects. F or male s u bjects i n partic ular, t he e x a mi nati o n is c o nsi dere d 
u n necessar y si nce it is n ot e x pecte d t o a d d a n y cli nic al val ue be y o n d w hat is alrea d y c o v ere d b y t h e 
meas ure me nts of t est oster o ne, l utei nizi n g h or m o n e ( L H), f ollicle -sti m ulati n g h or m o n e ( F S H), 
pr ostate s pecifi c a nti ge n ( P S A), 2 4 -h o ur uri ne c ollecti o n a n d uri nal ysis. T h e p h ysic al e xa mi nati o n 
of t he ge nit o -uri n ar y s yst e m will t heref ore be re m o ve d i n t he c urre nt pr ot o c ol u p date ( versi o n 3. 0).  
Secti o n # a n d n a me  
Descri pti o n of c h a n ge  
Brief r ati o n ale  
1 Pr ot oc ol s u m mar y  
1. 1 S y n o psis, pa ge 1 0  
P art 2  
T he t otal trial d urati o n f or t he 
i n di vi d ual s u bj ect will be 
a p pr o xi matel y 5 8  wee ks. P art 2 
c o nsists of a scree ni n g peri o d of 
a p pr o xi m atel y 2 w ee ks f oll o w e d b y  
t w o tre at me nt parts  
S pecif y t he scree ni n g peri o d i n P art 2 
of t he trial  
1. 2 Fl o wc hart P art 1 & P art 2  
 
Hi g hl y se nsiti ve uri ne P pre g na nc y 
test 
 
Clarificati o n t hat  o nl y  hi g hl y 
se nsiti ve uri ne pre g na nc y tests will be 
use d  
 
 
 
 
1 0. 2 A p pe n di x 2  
 
 
T a ble 1 0. 2 ( pa ge 7 6):  
Hi g hl y se nsiti ve ser u m h u ma n 
c h ori o nic g o na d otr o pi n ( h C G)  uri ne 
pre g na nc y test (as nee de d f or w o me n 
of c hil d beari n g p ote ntial)  
 
1 0. 4 A p pe n di x 4  
Pre g n a nc y testi n g  
•  
W o me n/ W O C B P s h o ul d o nl y be 
i ncl u de d after a ne gati ve hi g hl y 
se nsiti ve uri ne or ser u m  
pre g na nc y test  
•  
A d diti o nal ser u m hi g hl y 
se nsiti ve uri ne pre g na nc y testi n g 
f or W O C B P o nl y s h o ul d be 
perf or me d e ver y sec o n d wee k / 
f o urt h wee k d uri n g t he treat me nt 
peri o d, a n d at e n d of trial e n d of  
1 0. 9 A p pe n di x 9  
T a ble 1 0 -4  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
1 1 1
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 1 2  of 1 1 6  
 
Secti o n # a n d n a me  
Descri pti o n of c h a n ge  
Brief r ati o n ale  
1 0. 9. 4 Mi ni m u m assess me nts f or P art 
2 t o be perf or me d d uri n g l oc k d o w n  
Hi g hl y se nsiti ve uri ne p P re g na nc y 
test 
1. 2 Fl o wc hart  
Bi osa m ples f or F ut ure A nal ysis h 
8. 2. 1  1 0. 8  
Wr o n g li n k  
Secti o n 8. 2. 2 P h ysical E xa mi nati o n  
A p h ysical e xa mi nati o n will i ncl u de 
assess me nts of t he breast, hea d (ears, 
e yes, n ose, t hr oat a n d nec k), 
res pirat or y -, car di o vasc ular -, 
gastr oi ntesti nal (i ncl u di n g m o ut h) -, 
ge nit o -uri nar y  -, m usc ul os keletal - 
a n d ce ntr al a n d peri p heral ner v o us 
s yste m, s ki n, ge neral a p peara nce, 
l y m p h n o de pal pati o n, t h yr oi d gla n d 
a n d a b d o me n. as s pecifie d i n t he 
Fl o wc hart  
P h ysical e xa mi nati o n of t he ge nit o -
uri nar y s yste m is n ot re gar de d as 
i n dicate d f or b ot h fe male a n d male 
s u bj ects. F or male s u bj ects i n 
partic ular, t he e xa mi nati o n is n ot 
e x pecte d t o a d d a n y cli nical val ue 
be y o n d w hat is alrea d y c o vere d b y t he 
meas ure me nts of P S A, L H, F S H, 
test oster o ne, 2 4-h o ur uri ne c ollecti o n 
a n d uri nal ysis.  
T a ble 1 0 -2 Pr ot oc ol -re q uire d safet y 
la b orat or y assess me nts 
Bi oc he mistr y:  
• 
Ala ni ne A mi n otra nsferase ( A L T)  
• 
Al b u mi n  
• 
Al kali ne p h os p hatase  
• 
As partate A mi n otra nsferase 
( A S T) 
• 
Creati ni ne  
• 
P otassi u m  
• 
P h os p hate  
• 
S o di u m  
• 
T otal Bilir u bi n  
• 
T otal Calci u m  
• 
G G T  
• 
A m ylase  
• 
Li pase  
• 
Hs C R P  
• 
Ma g nesi u m  
• 
Plas ma  Ser u m  t otal pr otei n 
• 
Bl o o d urea nitr o ge n ( B U N) test  
C orrecti o n fr o m plas ma t o ser u m. 
Ser u m t otal pr otei n is a nal yse d i nstea d 
of plas ma t otal pr otei n  
Secti o n 1 0. 8 A p pe n di x 8 Rete nti o n of 
h u ma n bi osa m ples  
a n d  
Secti o n 8. 9 Bi osa m ples f or f ut ure 
researc h 
A p pe n di x 8  
S u bj ects ca n c o ntact t he i n vesti gat or if 
t he y wis h t o be i nf or me d a b o ut res ults 
deri ve d fr o m st ore d bi osa m ples 
o btai ne d fr o m t heir o w n b o d y.  
Secti o n 8. 9 Bi osa m ples f or f ut ure 
researc h 
T heref ore, a n y o utc o me of t he 
a nal yses will n ot be re p orte d directl y 
t o s u bj ects or sites. T he res ults ma y be 
re p orte d i n p u blicati o ns, at sci e ntific 
c o nfere nces or t o a ut h orities.  
T heref ore n o res ults fr o m a n al ysis 
perf or me d o n t hese s a m ples will be 
re p orte d t o sites or tri al s u bjects. 
M ore o ver, n o d at a a n al ysis or 
p u blic ati o ns will be p erf or me d o n 
p atie nt i de ntifi a ble d at a.  
Clarificati o n t hat n o res ults fr o m 
a nal ysis perf or me d o n bi osa m ples will 
be re p orte d t o sites or trial s u bj ects. 
M ore o ver, n o data a nal ysis or 
p u blicati o ns will be perf or me d o n 
patie nt i de ntifia ble data . 
 
N N 9 7 7 5- 4 7 0 8
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Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 1 3  of 1 1 6  
 
 
1 1  Refere nces  
1.  
N g M, Fle mi n g T, R o bi ns o n M, T h o ms o n B, Graetz N, Mar g o n o C, et al. Gl o bal, re gi o nal, 
a n d nati o nal pre v ale nce of o ver wei g ht a n d o besit y i n c hil dre n a n d a d ults d uri n g 1 9 8 0 -2 0 1 3: 
a s yste m atic a nal ysis f or t he Gl o bal B ur de n of Dis ease St u d y 2 0 1 3. La ncet. 
2 0 1 4; 3 8 4( 9 9 4 5): 7 6 6 -8 1.  
2.  
Afs hi n A, F or o uza nfar M H, Reits ma M B, S ur P, Este p K, Lee A, et al. Healt h Effects of 
O ver wei g ht a n d O besit y i n 1 9 5 C o u ntries o ver 2 5 Years. N E n gl J Me d. 2 0 1 7; 3 7 7( 1): 1 3 -2 7.  
3.  
H ofs ø D, J e nsse n T, Ha ger  H, R øislie n J, Hjel mesaet h J. Fasti n g plas ma gl uc ose i n t he 
scree ni n g f or t y pe 2 dia b etes i n m or bi dl y o bes e s u bjects. O bes S ur g. 2 0 1 0; 2 0( 3): 3 0 2 -7.  
4.  
M o k da d A H, F or d E S, B o w ma n B A, Nels o n D E, E n gel ga u M M, Vi nic or F, et al. Dia betes 
tre n ds i n t he U. S.: 1 9 90 -1 9 9 8. Dia betes Care. 2 0 0 0; 2 3( 9): 1 2 7 8 -8 3.  
5.  
P oirier P, Giles T D, Bra y G A, H o n g Y, Ster n J S, Pi -S u n yer F X, et al. O besit y a n d 
car di o vas c ular dise ase: p at h o p h ysi ol o g y, e val u ati o n, a n d effect of wei g ht l oss: a n u p date of 
t he 1 9 9 7 A merica n Heart Ass ociati o n Scie ntific State me nt o n O besit y a n d Heart Dise ase 
fr o m t he O besit y C o m mittee of t he C o u ncil o n N utriti o n, P h ysic al Acti vit y, a n d 
Meta b olis m. Circ ulati o n. 2 0 0 6; 1 1 3( 6): 8 9 8 -9 1 8.  
6.  
Bra y G A. Me dic al c o nse q ue nces of o besit y. J Cli n E n d ocri n ol Meta b. 2 0 0 4; 8 9( 6): 2 5 8 3 -9.  
7.  
G u h D P, Z h a n g W, Ba ns bac k N, A marsi Z, Bir mi n g ha m C L, A nis A H. T h e i nci de nce of c o -
m or bi dities relate d t o o besit y a n d o v er wei g ht: a s yste matic re vie w a n d meta -a nal ysis. B M C 
P u blic Healt h. 2 0 0 9; 9: 8 8.  
8.  
C usi K. R ole of o besit y a n d li p ot o xicit y i n  t he de v el o p me nt of n o nalc o h olic steat o he patitis: 
pat h o p h ysi ol o g y a n d cli nical i m plicati o ns. Gastr oe nter ol o g y. 2 0 1 2; 1 4 2( 4): 7 1 1 -2 5.e 6.  
9.  
Deitel M, St o ne E, Kassa m H A, Wil k EJ, S ut herla n d DJ. G y n ec ol o gic -o bst etric c ha n ges 
after l oss of massi ve e x cess wei g ht  f oll o wi n g b ari atric s ur ger y. J A m C oll N utr. 
1 9 8 8; 7( 2): 1 4 7 -5 3.  
1 0.  
E he ma n C, He nle y SJ, Ballar d -Bar bas h R, J ac o bs EJ, Sc h y m ur a MJ, N o o ne A M, et al. 
A n n ual Re p ort t o t he Nati o n o n t he stat us of ca ncer, 1 9 7 5 -2 0 0 8, feat uri n g ca ncers ass ociate d 
wit h e x cess we i g ht a n d l ac k of s ufficie nt p h ysical acti vit y. Ca ncer. 2 0 1 2; 1 1 8( 9): 2 3 3 8-6 6.  
1 1.  
Fle gal K M, Kit B K, Or pa na H, Gra u bar d BI. Ass ociati o n of All -Ca use M ortalit y Wit h 
O ver wei g ht a n d O besit y Usi n g Sta n dar d B o d y Mass I n d e x Cate g ories A S yste matic Re vie w 
a n d Meta-a nal ysis. J a ma -J o ur nal of t he A merica n Me dical Ass ociati o n. 2 0 1 3; 3 0 9( 1): 7 1-8 2.  
1 2.  
W hitl oc k G, Le wi n gt o n S, S herli ker P, Clar ke R, E m bers o n J, Halse y J, et al. B o d y -mass 
i n de x a n d ca use-s pecific m ortalit y i n 9 0 0 0 0 0 a d ults: c olla b orati ve a nal yses of 5 7 
pr o s pecti ve st u dies. La n cet. 2 0 0 9; 3 7 3( 9 6 6 9): 1 0 8 3-9 6.  
1 3.  
Zeller M H, H u nsa k er S, Mi k hail C, Reiter -P urtill J, Mc C ull o u g h M B, Garl a n d B, et al. 
Fa mil y fact ors t hat c haracteriz e a d olesce nts wit h se vere o b esit y a n d t heir r ole i n wei g ht l oss 
s ur ger y o utc o mes. O b esit y ( Sil ver S pri n g). 2 0 1 6; 2 4( 1 2): 2 5 6 2-9.  
1 4.  
Ha n T S, Tajar A, O' Neill T W, Jia n g M, Bartfai G, B o o ne n S, et al. I m p aire d q ualit y of life 
a n d se x ual f u ncti o n i n o ver wei g ht a n d o bese me n: t he E ur o pea n M ale A gei n g St u d y. E ur J 
E n d ocri n ol. 2 0 1 1; 1 6 4( 6): 1 0 0 3 -1 1.  
1 5.  
S ølt oft F, Ha m mer M, Kra g h N. T he ass o ciati o n of b o d y m ass i n de x a n d healt h -relate d 
q ualit y of life i n t he ge neral p o p ulati o n: data fr o m t he 2 0 0 3 Healt h S ur ve y of E n gl a n d. Q ual 
Lif e Res. 2 0 0 9; 1 8( 1 0): 1 2 9 3 -9.  
1 6.  
Mec ha nic k JI, Gar ber AJ, Ha n dels ma n Y, Ga r ve y W T. A merica n Ass ociati o n of Cli nical 
E n d ocri n ol o gists' p ositi o n state me nt o n o besit y a n d o besit y me dici ne. E n d o cr Pract. 
2 0 1 2; 1 8( 5): 6 4 2 -8.  
1 7.  
R o u n d -ta ble disc ussi o n o n o besit y a n d wei g ht l oss.  T here is n o mirac ul o us c ure b ut 
persiste nt p h ysici a ns ca n hel p m ost pe o ple t o re d u ce. N or d M e d. 1 9 7 5; 9 0( 5): 1 4 5 -5 3.  
N N 9 7 7 5- 4 7 0 8
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Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 1 4  of 1 1 6  
 
 
1 8.  
E ur o pea n Me dici nes A ge nc y, C o m mittee f or M e di ci nal Pr o d ucts f or H u ma n Use ( C H M P). 
G ui deli ne o n cli nical e val uati o n of me dici nal pr o d ucts use d i n wei g ht ma na ge m e nt 
( E M A/ C H M P/ 3 1 1 8 0 5/ 2 0 1 4). 2 3 J u n 2 0 1 6.  
1 9.  
Fr ü h bec k G, S braccia P, Nis oli E, W o o d war d E, Y u m u k V, Far p o ur -La m bert NJ, et al. 2 0 1 5 
Mila n Declarati o n: A Call t o Acti o n o n O besit y - a n E A S O P ositi o n State me nt o n t he 
Occasi o n of t h e 2 0 1 5 E X P O. O bes Facts. 2 0 1 6; 9( 4): 2 9 6 -8.  
2 0.  
K n o wler W C, Bar rett-C o n n or E, F o wler S E, Ha m ma n R F, Lac hi n J M, Wal ker E A, et al. 
Re d ucti o n i n t he i nci de nce of t y pe 2 dia betes wit h lifest yle i nter v e nti o n or metf or mi n. N 
E n gl J Me d. 2 0 0 2; 3 4 6( 6): 3 9 3 -4 0 3.  
2 1.  
Merte ns I L, V a n Gaal L F. O ver wei g ht, o b esit y, a n d bl o o d press ur e: t he effects of m o dest 
wei g ht r e d ucti o n. O bes R es. 2 0 0 0; 8( 3): 2 7 0 -8.  
2 2.  
Dattil o A M, Kris -Et hert o n P M. Effects of wei g ht re d ucti o n o n bl o o d li pi ds a n d li p o pr otei ns: 
a meta-a n al ysis. A m J Cli n N utr. 1 9 9 2; 5 6( 2): 3 2 0 -8.  
2 3.  
Vilar -G o mez E, Marti nez -Perez Y, Ca lza dilla-Bert ot L, T orres -G o nzalez A, Gra -Ora m as B, 
G o nzalez -Fa bia n L, et al. Wei g ht L oss T hr o u g h Lifest yl e M o dificati o n Si g nifica ntl y 
Re d uces Feat ur es of N o n alc o h olic Steat o he patitis. Gastr oe nter ol o g y. 2 0 1 5; 1 4 9( 2): 3 6 7 -7 8.  
2 4.  
War ke nti n L M, D as D, Maj u m dar  S R, J o h ns o n J A, Pa d wal R S. T he effect of wei g ht l oss o n 
healt h -rel ate d q ualit y of life: s yste matic re vie w a n d meta-a nal ysis of ra n d o mize d trials. 
O bes Re v. 2 0 1 4; 1 5( 3): 1 6 9 -8 2.  
2 5.  
Wi n g R R, P hela n S. L o n g -ter m wei g ht l oss mai nte na nce. A m J Cli n N utr. 2 0 0 5; 82( 1 
S u p pl): 2 2 2 S -5 S.  
2 6.  
O besit y is a Dis ease: Lea di n g O besit y Gr o u ps A gree [ press release]. 
htt ps:// w w w. pr ne ws wire. c o m/ ne ws -rel eases/ o besit y-is-a-diseas e -lea di n g-o b esit y -gr o u ps -
a gree -2 1 2 1 9 4 8 5 1. ht ml 1 9 J u n 2 0 1 3.  
2 7.  
T o pla k H, W o o d war d E, Y u m u k V, O p pert J M, Half or d J C, Fr ü h bec k G. 2 0 1 4 E A S O 
P ositi o n State me nt o n t he Use of A nti -O besit y Dr u gs. O b es Facts. 2 0 1 5; 8( 3): 1 6 6 -7 4.  
2 8.  
Fr u h bec k G, T o pla k H, W o o d war d E, Y u m u k V, Maisl os M, O p pert J M, et al. O besit y: t he 
gat e wa y t o ill healt h - a n E A S O p ositi o n state me nt  o n a risi n g p u blic h ealt h, cli nical a n d 
scie ntific c halle n ge i n E ur o pe. O bes Facts. 2 0 1 3; 6( 2): 1 1 7-2 0.  
2 9.  
A p o via n C M, Ar o n ne LJ, Besses e n D H, Mc D o n nell M E, M ura d M H, Pa g ott o U, et al. 
P har mac ol o gical ma n a ge me nt of o besit y: a n e n d o cri ne S ociet y cli nical pr actice g ui deli ne. J 
Cli n E n d ocri n ol Meta b. 2 0 1 5; 1 0 0( 2): 3 4 2 -6 2.  
3 0.  
Y u m u k V, Tsi g os C, Frie d M, Sc hi n dler K, B usett o L, Micic D, et al. E ur o pea n G ui deli nes 
f or O besit y Ma na ge me nt i n A d ults. O bes Facts. 2 0 1 5; 8( 6): 4 0 2-2 4.  
3 1.  
Clar ke W L, C o x DJ, G o n der -Fre d eri c k L A, J ulia n D, Sc hl u n dt D, P ol o ns k y W. Re d uce d 
a ware ness of h y p o gl yce mia i n a d ults wit h I D D M. A pr os pecti ve st u d y of h y p o gl yce mic 
fre q ue n c y a n d ass ociate d s y m pt o ms. Dia betes Care. 1 9 9 5; 1 8( 4): 5 1 7-2 2.  
3 2.  
Sc h mi dt J B, Gre gerse n N T, Pe derse n S D, Are nt oft J L,  Ritz C, Sc h wartz T W, et al. Effects 
of P Y Y 3 -3 6 a n d G L P -1 o n e ner g y i nta ke, e ner g y e x pe n dit ure, a n d a p petite i n o ver wei g ht 
me n. A m J P h ysi ol E n d ocri n ol Meta b. 2 0 1 4; 3 0 6( 1 1): E 1 2 4 8 -5 6.  
3 3.  
Talsa nia T, A ni ni Y, Si u S, Dr uc ker DJ, Br u ba ker P L. Peri p heral e xe n di n -4 a n d pe pti de 
Y Y( 3 -3 6) s y n er gisticall y re d uce f o o d i nta ke t hr o u g h differe nt mec ha nis ms i n mice. 
E n d ocri n ol o g y. 2 0 0 5; 1 4 6( 9): 3 7 4 8 -5 6.  
3 4.  
Batter ha m R L, C o wle y M A, S mall CJ, Herz o g H, C o he n M A, Da ki n C L, et al. G ut h or m o ne 
P Y Y( 3 -3 6) p h ysi ol o gicall y i n hi bits  f o o d i nta ke. Nat ure. 2 0 0 2; 4 1 8( 6 8 9 8): 6 5 0-4.  
3 5.  
A b b ott C R, S mall CJ, Ke n ne d y A R, Near y N M, Saje di A, G hatei M A, et al. Bl oc ka d e of t he 
ne ur o pe pti de Y Y 2 rece pt or wit h t he s pecific a nt a g o nist BII E 0 2 4 6 atte n u ates t he effect of 
e n d o ge n o us a n d e x o ge n o us pe pti d e Y Y( 3-3 6) o n f o o d i nta ke. Brai n Res. 2 0 0 5; 1 0 4 3( 1 -
2): 1 3 9 -4 4.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
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Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 1 5  of 1 1 6  
 
 
3 6.  
A/ S N N. I n v esti gat or's Br oc h ure, n n c 0 1 6 5 -1 8 7 5 f or wei g ht ma na ge m e nt, pr oject N N 9 7 7 5 
(e diti o n 2). 0 8 J a n 2 0 2 1. 
3 7.  
G utz willer J P, Dre we J, G o ke B, Sc h mi dt H, R o hrer B, Larei da J, et al. Gl uca g o n -li ke 
pe pti de -1 pr o m otes satiet y a n d re d uces f o o d i nta ke i n patie nts wit h dia betes mellit us t y pe 2. 
A m J P h ysi ol. 1 9 9 9; 2 7 6( 5 Pt 2): R 1 5 4 1 -4.  
3 8.  
N o v o N or dis k A/ S. I n v esti gat or's  Br oc h ure, Se ma gl uti de s.c. 2. 4 m g f or wei g ht 
ma na ge me nt, pr oje cts N N 9 5 3 6 a n d E X 9 5 3 6  (e diti o n 6). 0 3 Dec 2 0 2 0. 
3 9.  
K DI G O. K DI G O 2 0 1 2 Cli nical Practice G ui deli ne f or t he E val uati o n a n d Ma na ge me nt of 
C hr o nic Ki d ne y Diseas e. 0 1 J a n 2 0 1 3.  
4 0.  
Ba n ks P A, B olle n T L, D er ve nis C, G o osze n H G, J o h ns o n C D, Sarr M G, et al. Classificati o n 
of ac ut e p a ncreatitis -2 0 1 2: re visi o n of t he Atla nta classificati o n a n d defi niti o ns b y 
i nter nati o nal c o nse ns us. G ut. 2 0 1 3; 6 2( 1): 1 0 2-1 1.  
4 1.  
Kr oe n ke K, S pitz er R L, Willia ms J B. T he P H Q -9 - Vali dit y of a brief de pressi o n se verit y 
meas ure. J Ge n I nter n Me d. 2 0 0 1; 1 6( 9 ): 6 0 6-1 3.  
4 2.  
P os ner K, O q ue n d o M A, G o ul d M, Sta nle y B, Da vies M. C ol u m bia Classificati o n 
Al g orit h m of S uici de Assess me nt ( C -C A S A): classificati o n of s uici dal e ve nts i n t he F D A's 
pe diatric s uici dal ris k a n al ysis of a nti de pressa nts. A m J Ps yc hiatr y. 2 0 0 7; 1 6 4( 7): 1 0 3 5 -4 3.  
4 3.  
Mc E v o y B W. Missi n g data i n cli nical trials f or wei g ht ma na ge me nt. J Bi o p har m Stat. 
2 0 1 6; 2 6( 1): 3 0 -6.  
4 4.  
W orl d Me dical Ass ociati o n. W M A Declarati o n of Helsi n ki - Et hical Pri nci ples f or Me dical 
Researc h I n v ol vi n g H u ma n S u bjects. Last a me n de d b y t he 6 4t h W M A Ge n eral Asse m bl y, 
F ortaleza, Brazil. Oct o ber 2 0 1 3.  
4 5.  
I C H Har m o nise d Tri p artite G ui deli ne. G ui deli ne f or G o o d Cli nical Practice E 6( R 2), Ste p 4 
versi o n. 0 9 N o v 2 0 1 6.  
4 6.  
De A n gelis C, Draze n J M, Frizelle F A, Ha u g C, H oe y J, H ort o n R, et a l. Cli nical trial 
re gistrati o n: a state me nt fr o m t he I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors. N 
E n gl J Me d. 2 0 0 4; 3 5 1( 1 2): 1 2 5 0 -1.  
4 7.  
U. S. De part me nt of Healt h a n d H u ma n Ser vices, F o o d a n d Dr u g A d mi nistrati o n. F o o d a n d 
Dr u g A d mi nistrati o n A me n d me nts Act of 2 0 0 7 as a me n de d b y t he Fi nal R ule " Cli nical 
Trials Re gistrati o n a n d Res ults I nf or mati o n S u b missi o n". 2 1 Se pte m ber 2 0 1 6.  
4 8.  
T he E ur o pea n Parlia me nt a n d t he C o u ncil of t he E ur o pea n C o u ncil. Directi ve 2 0 0 1/ 2 0/ E C 
of t he E ur o pea n Parlia me nt a n d of t he C o u ncil of 4 A pril 2 0 0 1 o n t he a p pr o xi mati o n of t he 
la ws, re g ulati o ns a n d a d mi nistrati ve pr o visi o ns of t he me m ber states relati n g t o t he 
i m ple me ntati o n of g o o d cli nical practice i n t he c o n d uct of cli nical trials o n me dici nal 
pr o d ucts f or h u ma n us e. 2 0 0 1 . 
4 9.  
T he E ur o pea n Parlia me nt a n d t he C o u ncil of t he E ur o pea n C o u ncil. Re g ulati o n ( E C) N o 
7 2 6/ 2 0 0 4 of t he E ur o pea n Parlia me nt a n d of t he C o u ncil of 3 1 Marc h 2 0 0 4 la yi n g d o w n 
C o m m u nit y pr oce d ures f or t he a ut h orisati o n a n d s u per visi o n of me dici nal pr o d ucts f or 
h u ma n a n d veteri n ar y us e a n d esta blis hi n g a E ur o pea n Me dici nes A ge nc y, article 5 7. 3 0 
A pril 2 0 0 4.  
5 0.  
T he E ur o pea n Parlia me nt a n d t he C o u ncil of t he E ur o pea n C o u ncil. Re g ulati o n ( E C) N o 
1 9 0 1/ 2 0 0 6 of t he E ur o pea n Parlia me nt a n d of t h e C o u ncil of 1 2 Dece m b er 2 0 0 6 o n 
me dici nal pr o d ucts f or p ae diatric us e a n d a me n di n g Re g ulati o n ( E E C) N o 1 7 6 8/ 9 2, 
Directi ve 2 0 0 1/ 2 0/ E C, Directi ve 2 0 0 1/ 8 3/ E C a n d Re g ulati o n ( E C) N o 7 2 6/ 2 0 0 4, article 4 1. 
Official J o ur nal of t he E ur o pea n C o m m u nities. 2 7 Dec 2 0 0 6.  
5 1.  
E dit ors I C o MJ. Rec o m me n dati o ns f or t he C o n d uct, Re p orti n g, E diti n g a n d P u blicati o n of 
Sc h olarl y W or k i n Me dic al J o ur nals 2 0 1 9.  
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
1 1 5
1 1 6
C O N FI D E N TI A L

Pr ot o c ol  
C O N FI D E N TI A L  
Date:  
0 5 A pril 2 0 2 2  N o v o N or di s k  
Trial I D: N N 9 7 7 5 -4 7 0 8  
V ersi o n:  
4. 0  
      
Stat us:  
Fi n al  
      
P a ge:  
1 1 6  of 1 1 6  
 
 
5 2.  
I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors. Rec o m me n dati o ns f or t he C o n d uct, 
Re p orti n g, E diti n g a n d P u blicati o n of Sc h olarl y W or k i n Me dical J o ur nals; c urre nt versi o n 
a vaila ble at w w w.ic mje. or g.  
5 3.  
Scialli A R, Baile y G, Be yer B K, B ø g h I B, Bresli n WJ, C he n C L, et al. P ote ntial se mi nal 
tra ns p ort of p har mace uti cals t o t he c o nce pt us. Re pr o d T o xic ol. 2 0 1 5; 5 8: 2 1 3-2 1.  
 
 
N N 9 7 7 5- 4 7 0 8
N N 9 7 7 5
0
 |
V V- T M F- 5 0 4 2 3 4 5
 .
-
 |
1
 |
 of
  Pr ot oc ol  versi o n 4. 0
1 1 6
1 1 6
C O N FI D E N TI A L