Phase 3, Single-administration, Open-label Trial to Assess the Efficacy, Safety, PK, and PD of Dasiglucagon When Administered as a Rescue Therapy for Severe Hypoglycemia in Pediatric Patients Below 6 Years of Age With Type 1 Diabetes (T1D)
Phase: PHASE3
Conditions: Hypoglycemia, Type 1 Diabetes
Sponsor: Zealand Pharma

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 1 /7 8  
C O N FI D E N T I A L  
Title P a ge  
Pr ot oc ol Title:  A P has e  3, si n gle -a d mi nistrati o n, o pe n -la bel trial t o ass ess t he efficac y, safet y, 
p har mac o ki netics , a n d p har mac o d y n a mics  of dasi gl uca g o n w he n a d mi nistere d as a resc u e 
t hera p y f or s e vere h y p o gl yce mia  i n pe diatric  p atie nts bel o w  6  years of a ge  wit h T y pe 1  D ia betes 
( T 1 D) 
Pr ot oc ol N u m ber:  
Z P 4 2 0 7 -2 1 0 5 2  
Pr ot oc ol V ersi o n a n d D ate:  Ori gi nal V ersi o n 1. 0 -1 0  Mar  2 0 2 2  
Versi o n 2. 0, 1 4 Oct 2 0 2 2  
Versi o n  3 . 0, 1 2  Dec  2 0 2 2  
Versi o n 4. 0, 0 9  Mar 2 0 2 3  
Versi o n 5. 0, 0 1 N o v 2 0 2 3  
Versi o n 6. 0, 1 2  J ul 2 0 2 4 
C o m p o u n d:  Dasi gl uca g o n  
Tri al  P h ase:  P hase  3  
S p o ns or N a me:  Zeala n d P har ma A/ S  
Le g al Re gistere d A d dress:  C V R N o. D K 2 0 0 4 5 0 7 8  
S y d mar ke n 1 1  
D K -2 8 6 0 S ø b or g  
De n mar k  
Re g ul at or y A ge nc y I de ntifier N u m ber(s)  
I N D: 1 2 7 8 6 6  
A p pr o v al D ate:  1 2  J ul 2 0 2 4  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 2 /7 8  
C O N FI D E N T I A L  
S p o ns or Si g n at or y:  
 
 M D  
 
 
 
D ate  
 
 
 
D ate  
 M Sc St atistici a n
 
 
 
D ate  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 3 /7 8  
C O N FI D E N T I A L  
T a ble of C o nte nts  
Ta ble of C o nte nts  ............................................................................................................................ 3  
1  
P R O T O C O L S U M M A R Y  ...................................................................................................... 9  
1. 1  S y n o psis  .............................................................................................................................. 9  
1. 2  Sc he ma  .............................................................................................................................. 1 2  
1. 3  Sc he d ule of As sess me nts .................................................................................................. 1 3  
2  
I N T R O D U C TI O N ................................................................................................................ 1 6  
2. 1  Trial Rati o nale  .................................................................................................................. 1 6  
2. 2  Bac k gr o u n d  ....................................................................................................................... 1 6  
2. 3  Be nefit/ Ris k Assess me nt  .................................................................................................. 1 8  
3  
O BJ E C TI V E S A N D E N D P OI N T S  ...................................................................................... 2 0  
4  
T RI A L D E SI G N  ................................................................................................................... 2 1  
4. 1  O verall Desi g n  .................................................................................................................. 2 1  
4. 2  Scie ntific Rati o nale f or Trial Desi g n  ................................................................................ 2 2  
4. 3  J ustificati o n f or D ose ........................................................................................................ 2 2  
4. 3. 1  P har mac o ki netics  ...................................................................................................... 2 3  
4. 3. 2  Car diac re p olariz ati o n a n d dasi gl uca g o n c o nce ntrati o n  ........................................... 2 3  
4. 3. 3  Safet y  ........................................................................................................................ 2 4  
4. 4  E n d -of -Tri al Defi niti o n  ..................................................................................................... 2 5  
5  
T RI A L P O P U L A TI O N  ......................................................................................................... 2 6  
5. 1  I n cl usi o n Criteria .............................................................................................................. 2 6  
5. 2  E xcl usi o n Criteria  ............................................................................................................. 2 6  
5. 3  Lifest yle C o nsi derati o ns  ................................................................................................... 2 7  
5. 3. 1  Meals a n d Dietar y Restri cti o ns ( Visit  2)  .................................................................. 2 7  
5. 3. 2  Acti vit y  ..................................................................................................................... 2 8  
5. 4  Scree n Fail ures  .................................................................................................................. 2 8  
5. 5  Crit eria f or T e m p oraril y Dela yi n g E nr oll me nt a n d A d mi nistrati o n of Trial I nter ve nti o n  2 8  
6  
T RI A L I N T E R V E N TI O N( S) A N D C O N C O MI T A N T T H E R A P Y  .................................... 2 9  
6. 1  Trial I nter v e nti o n(s) A d mi nistere d  ................................................................................... 2 9  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 4 /7 8  
C O N FI D E N T I A L  
6. 1. 1  Me dical De vic es ........................................................................................................ 3 0  
6. 2  Pre parati o n/ Ha n dli n g/ St ora ge/ Acc o u nta bilit y  .................................................................. 3 1  
6. 3  Trial I nter v e nti o n C o m plia nce  .......................................................................................... 3 1  
6. 4  D ose M o dificati o n  ............................................................................................................ 3 2  
6. 4. 1  Retreat me nt Criteria  .................................................................................................. 3 2  
6. 5  Treat me nt a n d D osi n g C o n diti o ns  .................................................................................... 3 2  
6. 5. 1  H y p o gl yce mic Cla m p Pr oce d ure a n d D osi n g  ........................................................... 3 2  
6. 5. 2  Resc ue Pr o visi o ns f or H y p o gl yce mia  ....................................................................... 3 5  
6. 5. 3  C ollecti o n of Bl o o d Sa m ples  .................................................................................... 3 5  
6. 6  C o nti n ue d Access t o Trial I nter ve nti o n After Visit  2  ....................................................... 3 7  
6. 7  Treat me nt of O v er d ose  ..................................................................................................... 3 7  
6. 8  C o nc o mita nt T hera p y ........................................................................................................ 3 7  
7  
DI S C O N TI N U A TI O N O F T RI A L I N T E R V E N TI O N A N D P A TI E N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L  ............................................................................ 3 8  
7. 1  Disc o nti n uati o n of Trial I nter ve nti o n  ............................................................................... 3 8  
7. 2  Patie nt Disc o nti n uati o n/ Wit h dra wal fr o m t he Tri al  ......................................................... 3 8  
7. 3  L ost t o F oll o w -U p  ............................................................................................................. 3 8  
8  
T RI A L A S S E S S M E N T S A N D P R O C E D U R E S  ................................................................. 4 0  
8. 1  Assess me nts a n d Sc he d ule of Meas ure me nts  ................................................................... 4 0  
8. 1. 1  Scree ni n g Visit  .......................................................................................................... 4 0  
8. 1. 2  D osi n g Visit  .............................................................................................................. 4 1  
8. 1. 3  F oll o w -u p Visit  ......................................................................................................... 4 2  
8. 2  Safet y Assess me nts  ........................................................................................................... 4 3  
8. 2. 1  P h ysical E xa mi nati o ns  .............................................................................................. 4 3  
8. 2. 2  Vital Si g ns  ................................................................................................................. 4 3  
8. 2. 3  Electr ocar di o gra ms  ................................................................................................... 4 3  
8. 2. 4  L ocal T olera bilit y ...................................................................................................... 4 3  
8. 2. 5  Cli nical Safet y La b orat or y Assess me nts  .................................................................. 4 4  
8. 3  A Es, S A Es, a n d Ot her Safet y Re p orti n g  .......................................................................... 4 4  
8. 3. 1  Ti me Peri o d a n d Fre q ue n c y f or C ollecti n g A E a n d S A E I nf or mati o n  ..................... 4 4  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 5 /7 8  
C O N FI D E N T I A L  
8. 3. 2  Met h o d of Dete cti n g A Es a n d S A Es  ........................................................................ 4 4  
8. 3. 3  F oll o w -u p of A Es a n d S A Es  ..................................................................................... 4 4  
8. 3. 4  Re g ulat or y Re p orti n g Re q uire me nts f or S A Es  ......................................................... 4 5  
8. 3. 5  A Es of S pecial I nterest .............................................................................................. 4 5  
8. 3. 6  H y p o gl yce mia  ........................................................................................................... 4 5  
8. 3. 7  H y perse nsiti vit y  ........................................................................................................ 4 6  
8. 3. 8  Ot her I m p orta nt E v e nts  ............................................................................................. 4 6  
8. 3. 9  Ha n dli n g of Tec h ni cal C o m plai nts Re gar di n g Dasi gl uca g o n Pre -fille d S yri n ges ... 4 6  
8. 4  P har mac o ki netics  .............................................................................................................. 4 7  
8. 5  P har mac o d y na mics  ........................................................................................................... 4 7  
8. 6  I m m un o ge nicit y Assess me nts  ........................................................................................... 4 8  
9  
S T A TI S TI C A L C O N SI D E R A TI O N S .................................................................................. 4 9  
9. 1  Statistical H y p ot heses  ....................................................................................................... 4 9  
9. 2  Sa m ple Size Deter mi nati o n ............................................................................................... 4 9  
9. 3  A nal ysis Sets  ..................................................................................................................... 4 9  
9. 4  Statistical A nal yses  ........................................................................................................... 4 9  
9. 4. 1  Ge neral C o nsi derati o ns  ............................................................................................. 4 9  
9. 4. 2  Pri mar y E n d p oi nt  ...................................................................................................... 5 0  
9. 4. 3  Sec o n dar y E n d p oi nts  ................................................................................................ 5 0  
9. 5  I nteri m A nal ysis ................................................................................................................ 5 1  
1 0  S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L C O N SI D E R A TI O N S  ....... 5 2  
1 0. 1  A p pe n di x 1: Re g ulat or y, Et hical, a n d Trial O v ersi g ht C o nsi derati o ns  ............................ 5 2  
1 0. 1. 1  Re g ulat or y a n d Et hical C o nsi derati o ns  ..................................................................... 5 2  
1 0. 1. 2  Fi na ncial Discl os ur e .................................................................................................. 5 2  
1 0. 1. 3  I nf or me d C o nse nt Pr ocess ........................................................................................ 5 2  
1 0. 1. 4  Data Pr otecti o n .......................................................................................................... 5 3  
1 0. 1. 5  C o m mittees Str uct ure ................................................................................................ 5 3  
1 0. 1. 6  Pr ot oc ol De viati o ns  ................................................................................................... 5 5  
1 0. 1. 7  Pr ot oc ol C ha n ges  ...................................................................................................... 5 5  
1 0. 1 . 8 S o urce D oc u m e nts  .................................................................................................... 5 6  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 6 /7 8  
C O N FI D E N T I A L  
1 0. 1. 9  Electr o nic Case Re p ort F or ms  .................................................................................. 5 6  
1 0. 1. 1 0  
Disse mi nati o n of Cli nical Trial Data  ................................................................. 5 7  
1 0. 1. 1 1  
Rete nti o n of Trial Rec or ds  ................................................................................. 5 8  
1 0. 1. 1 2  
Trial a n d Site Start a n d Cl os ure  ......................................................................... 5 8  
1 0. 1. 1 3  
P u blicati o n P olic y  .............................................................................................. 5 9  
1 0. 2  A p pe n di x 2: Cli nical La b orat or y Tests  ............................................................................. 6 1  
1 0. 3  A p pe n di x 3: A d verse E v e nts a n d Seri o us 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 n g, F oll o w -u p, a n d Re p orti n g  ................................................................... 6 2  
1 0. 3. 1  Defi niti o n of A d vers e E v e nt  ..................................................................................... 6 2  
1 0. 3. 2  Defi niti o n of S A E  ..................................................................................................... 6 3  
1 0. 3. 3  C ollecti o n, Rec or di n g, a n d Re p orti n g of A Es  .......................................................... 6 5  
1 0. 3. 4  F oll o w -u p of A Es  ...................................................................................................... 6 5  
1 0. 4  A p pe n di x 5: A b bre viati o ns a n d Defi niti o ns  ..................................................................... 6 8  
1 0. 5  A p pe n di x 6: List of Na mes a n d A d dresses  ....................................................................... 7 0  
1 0. 6  A p pe n di x 7: S u m mar y of C ha n ges fr o m Versi o n 4 t o Versi o n 5  ..................................... 7 2  
1 1  R E F E R E N C E S  ..................................................................................................................... 7 8  
 
 
 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 7 /7 8  
C O N FI D E N T I A L  
I n de x of In -te xt T a bles  
Ta ble  1 -1  
Sc he d ule of Assess me nts  .......................................................................................... 1 3  
Ta ble  6 -1  
I d e ntificati o n of Tri al I nter ve nti o n ........................................................................... 3 0  
Ta ble  6 -2  
I ns uli n I nf usi o n Rates ............................................................................................... 3 3  
Ta ble  6 -3  
Bl o o d V ol u mes  ......................................................................................................... 3 6  
Ta ble  6 -4  
P D (f or efficac y) a n d P K Sa m pli n g Base d o n B o d y Wei g ht  .................................... 3 6  
 
 
 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 8 /7 8  
C O N FI D E N T I A L  
I n de x of In -te xt F i g ures 
Fi g ure  4 -1  Trial Desi g n  .............................................................................................................. 2 2  
Fi g ure  6 -1  I ns uli n-I n d u ce d H y p o gl y ce mia a n d D osi n g ............................................................. 3 4  
 
 
 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 9 /7 8  
C O N FI D E N T I A L  
1  
P R O T O C O L S U M M A R Y  
1. 1  S y n o psis  
Pr ot oc ol Title:  
A P hase  3, si n gle-a d mi nistrati o n  o pe n -la bel trial t o assess t he efficac y, safet y, p har mac o ki n etics , 
a n d p har mac o d y na mics of dasi gl uca g o n w he n a d mi nistere d as a resc ue t h era p y f or 
h y p o gl yce mia i n pe diatri c patie nts bel o w  6  years of a ge  wit h T y pe 1 D ia betes ( T 1 D). 
R ati o n ale:  
Dasi gl uca g o n is i n dicate d f or treat me nt of se vere h y p o gl yce mia i n pe diatri c a n d a d ult patie nt s 
wit h dia betes a ge d 6  y ears a n d a b o ve. As t his c o n diti o n als o affects c hil dre n bel o w 6  years of 
a ge a n d t here is a t hera pe utic nee d f or t h e m t o get access t o safe  a n d efficaci o us e mer ge nc y 
treat me nt, t he pres e nt trial ai ms t o assess t he efficac y a n d safet y of a si n gle s u bc uta ne o us ( S C) 
i njecti o n of dasi gl uca g o n i n c hil dre n bel o w 6 years of a ge wit h T 1 D . A t otal of 8  c hil dre n will be 
i ncl u de d; 4 c hil dre n recei vi n g a  d ose of 0. 3  m g a n d 4 c hil dre n recei vi n g a d ose of 0. 6 m g. Of t he 
4 c hil dre n recei vi n g 0. 3  m g , 2 c hil dre n s h o ul d prefera bl y be bel o w 2 y ears at scree ni n g. T h e 
re mai ni n g 2 c hil dre n a ge d 2 years or a b o ve recei vi n g 0. 3 m g s h o ul d prefera bl y  be bel o w 4 years  
at scree ni n g . F or c hil dre n recei vi n g t he 0. 6  m g  d os e , all m ust be a b o ve 2 years at scree ni n g. T he 
trial p o p ulati o n will i ncl u de c hil dre n tr eate d wit h S C i ns uli n i nf usi o n via i ns uli n p u m p  or 
m ulti ple dail y i njecti o ns  i n or der t o i ncl u de c hil dre n bel o w 1  year  of a ge . O verall, t he eli gi bilit y 
criteria all o w f or e nr ol l me nt of a trial p o p ulati o n rese m bli n g t he tar get p o p ulati o n of c hil dre n 
bel o w  6  years of a g e  wit h T 1 D.  
O bjecti ves a n d E n d p oi nts:  
O bjecti ves  
E n d p oi nts  
T o assess  t he efficac y of 
dasi gl uca g o n i njecti o n i n 
c hil dre n <  6  years of a ge  wit h 
T 1 D  
Pri mar y e n d p oi nt  is p har mac o d y na mics ( P D): 
Plas ma gl uc ose c ha n ge fr o m baseli ne at 3 0  mi n utes after I M P i njecti o n 
or at t he ti me of resc ue b y i ntra ve n o us (I V) gl uc ose  
Sec o n dar y e n d p oi nt  is P D *: 
P las ma gl uc ose c ha n ge fr o m baseli ne at 1 5 mi n utes after I M P i njecti o n 
or at t he ti me of resc ue b y I V gl uc ose  
T o assess P K of dasi gl uca g o n 
i n c hil dre n wit h T 1 D 
P K e n d p oi nts will be deri ve d fr o m plas ma dasi gl uca g o n pr ofiles fr o m 
0 t o 3 0 0  mi n utes *.  
•  
A U C fr o m 0 t o 3 0  mi n utes p ost -d ose ( A U C 0 -3 0 mi n) 
•  
A U C  fr o m 0 t o 3 0 0 mi n utes p ost -d ose ( A U C 0 -3 0 0 mi n) 
•  
A U C fr o m 0 t o t he last ti me p oi nt wit h a meas ure d 
c o nce ntrati o n  ( A U C0 -t) 
•  
A U C fr o m 0 t o i nfi nit y p ost -d ose ( A U C i nf) 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 1 0 /7 8  
C O N FI D E N T I A L  
O bjecti ves  
E n d p oi nts  
•  
Ma xi m u m o bser ve d c o nce ntrati o n ( C
ma x ) 
•  
Ti me t o C ma x  ( Tma x ) 
•  
Ter mi nal eli mi nati o n rate c o nsta nt of plas ma dasi gl uca g o n 
( λz) 
•  
Ter mi nal plas ma eli mi nati o n half -life of dasi gl uca g o n (t½ ) 
•  
T otal b o d y cleara nce of plas ma dasi gl uca g o n ( Cl/f)  
•  
V ol u me of distri b uti o n of plas ma dasi gl uca g o n ( Vz/f)  
•  
Mea n resi de nce ti me of plas ma dasi gl uca g o n ( M R T)  
T o assess t he safet y pr ofile of 
dasi gl uca g o n i n c hil dre n wit h 
T 1 D  
•  
A d verse e ve nts  
•  
A d mi nistrati o n of resc ue I V gl uc ose i nf usi o n wit hi n 
3 0  mi n utes  of  I M P i njecti o n 
•  
Ti me t o first I V gl uc ose i nf usi o n f oll o wi n g treat me nt wit h 
dasi gl uca g o n wit hi n 3 0  mi n utes  
 
Ot her e n d p oi nts  
•  
A nti -dr u g a nti b o dies  
A b bre viati o ns: A D A =a nti -dr u g a nti b o dies; A U C = plas ma c o nce ntrati o n vers us ti me c ur ve; I M P =i n vesti gati o nal 
me dici nal pr o d uct; I V =i ntra ve n o us; P D = p har mac o d y na mics; P K = p har mac o ki netics ; T 1 D = T y pe  1 dia betes  
* as t he sa m pli n g fre q ue nc y f or P K  a n d  P D will gra d uall y be re d uce d w it h l o wer wei g ht f or c hil dre n of 1 0 k g a n d 
bel o w (as s pecifie d i n Ta ble  6 -4 ), t hese mar ke d e n d p oi nts will be assesse d t o t he e xte nt p ossi ble base d o n t he 
sa m ples o btai ne d f or t he i n di vi d ual c hil d.   
 
O ver all Desi g n:  
T his trial will use a  si n gle-a d mi nistrati o n , o pe n-label trial desi g n t o assess t he a bilit y of a si n gle 
S C i njecti o n of  dasi gl uca g o n t o i ncrease pl as ma gl uc ose i n pe diatric c hil dre n  wit h T 1 D  wit h 
h y p o gl yce mi a. A t otal of 8  c hil dre n will be i ncl u d e d; 4 c hil dre n recei vi n g a d ose of 0. 3 m g a n d 
4  c hil dre n recei vi n g a d ose of 0. 6 m g. Of t he 4 c hil dre n recei vi n g 0. 3 m g , 2 c hil dre n s h o ul d 
prefera bl y  be b el o w 2 years at scree ni n g. T he  re m ai ni n g 2 c hil dre n a ge d 2 years or a b o ve 
recei vi n g 0. 3 m g s h o ul d prefera bly  be b el o w 4 years  at scree ni n g. F or c hil dre n recei vi n g t he 0. 6 
m g d ose, all m ust be a b o ve 2 years at scree ni n g. Bef ore a n eli gi ble c hil d is d ose d, t he d ose le vel 
( 0. 6 m g or 0. 3  m g) m ust be c o nfir me d b y t h e sp o ns or . Eac h c hil d will be d ose d after t h e safet y 
assess me nt of t he prece di n g c hil d has bee n c o m plete d a n d assesse d b y t h e Trial Safet y Gr o u p.  
T he trial will i ncl u de t he f oll o wi n g visits:  
•  A scree ni n g visit ( Visit 1) i n t he peri o d fr o m Da y ‑ 5 0 t o Da y ‑ 2 9 ( pre-tr eat me nt visit) 
•  A d osi n g visit  ( Visit 2), Da y  1 ( da y of si n gle d osi n g wit h i n vesti gati o nal me dici nal 
pr o d uct [ I M P]) 
•  A Safet y  f oll o w-u p visit ( Visit 3) at Da y 2 9 + 5  d a ys (t he e n d -of -trial visit) 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 1 1 /7 8  
C O N FI D E N T I A L  
T he pri mar y e n d p oi nt of t he trial is plas ma gl uc ose c ha n g e fr o m bas eli ne at 3 0  mi n utes after I M P 
i njecti o n or at t he ti me of resc ue b y i ntra ve n o us gl uc ose . P har mac o d y na mics ( P D) i.e., p las ma 
gl uc ose will be assesse d at baseli ne  a n d 1 5 a n d 3 0  mi n utes  after d osi n g , w hile t he gl uc ose le vels 
will be m o nit ore d b y c o nti n u o us gl uc ose m o nit ori n g a n d b y a plas ma gl uc ose a nal yzer  d uri n g t he 
d osi n g visit  ( Visit 2). P har mac o ki netics ( P K ) will be assessed  t hr o u g h o ut a 3 0 0 -mi n ute peri o d  at 
t he d osi n g visit ( Visit 2). Safet y will be assesse d pri or t o d osi n g a n d t hr o u g h o ut a 3 0 0 -mi n ute  
peri o d after d osi n g  a n d a gai n at t he f oll o w-u p visit.  
Brief S u m m ar y:  
T he p ur p ose of t his trial is t o assess efficac y, safet y , P K , a n d P D of a si n gle S C i njecti o n of 
dasi gl uca g o n as a resc u e t hera p y f or h y p o gl yce mi a i n pe diatric c hil dre n  (<  6  years of a ge ) wit h 
T 1 D . Trial details i ncl u d e:  
•  Trial D urati o n: Ma xi m u m of 8 4  da ys  
•  Treat me nt D urati o n: 1  da y ( d osi n g visit  [V isit 2 ]) 
•  T otal of 3 visits  
N u m ber of P atie nt s: 
At least 8  c hil dre n bel o w  6 years (at t he scree ni n g visit) wit h T 1 D  will be d ose d i n t he trial. 
T w o  of t hese c hil dre n s h o ul d prefera bl y be bel o w 2  years of a ge  at t he s cree ni n g  visit  a n d 
s uccessf ull y c o m plete V isit 2 . F urt her m ore , t h e re mai ni n g 2 c hil dre n s h o ul d prefera bly  be b el o w 
4 years .  
I nter ve nti o n Gr o u ps a n d D ur ati o n: 
All 8  c hil dre n will be treate d wit h dasi gl uca g o n via a si n gle S C i njecti o n i nt o t he b utt oc ks at t he 
d osi n g visit ( Visit  2).   
F o ur c hil dre n i n t he a ge ra n ge ≥ 2 a n d < 6 y ears : 
•  will recei ve a si n gle S C i njecti o n  of 0. 6  m g/ 0. 6 m L of dasi gl uca g o n  b y a prefille d s yri n ge . 
F o ur c hil dre n , 2 of w hic h s h o ul d prefera bl y be bel o w 2 years , a n d t he c hil dre n a ge d ≥ 2 y ears  
a n d prefera bl y < 4 years : 
•  will recei ve a si n gle S C i njecti o n  of 0. 3 m g/ 0. 3 m L dasi gl uca g o n b y a s yri n ge  
St atistic al Met h o ds:  
T he pri mar y effic ac y e n d p oi nt will be s u m marize d usi n g descri pti ve statistics a n d a 9 5 % 
c o nfi de nce i nter val. Ot h er e n d p oi nts will be s u m marize d usi n g des cri pti ve statistics. All data will 
be liste d.  
D at a M o nit ori n g: Yes , T rial S afet y G r o u p. 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 1 2 /7 8  
C O N FI D E N T I A L  
1. 2  Sc he m a  
 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 1 5 /7 8  
C O N FI D E N T I A L  
g  
L ocal t olera bilit y assesse d at 3 0, 1 2 0, a n d 3 0 0  mi n utes after d osi n g. T he act ual ti me of t he assess me nt s h o ul d n ot de viate fr o m t he n o mi nal ti me b y m ore t ha n 
±  1 0  mi n utes.  
h  
T he act ual ti me of bl o o d sa m pli n g s h o ul d n ot de viate fr o m t he n o mi nal ti me b y m ore t ha n ±  1  mi n ute. Pre -d ose is defi ne d as wit hi n 2  mi n utes pri or t o d osi n g. 
Refer t o Ta ble  6 -4  f or p har mac o ki netic sa m pli n g base d o n b o d y wei g ht at Visit 2. 
i 
T he act ual ti me of bl o o d sa m pli n g s h o ul d n ot de viate fr o m t he n o mi nal ti me b y m ore t ha n ±  1  mi n ute f or t he c ollecti o n ti me p oi nts. Pre -d ose is defi ne d as 
wit hi n 2  mi n utes pri or t o d osi n g. Refer t o Ta ble  6 -4  f or plas ma gl uc ose sa m pli n g base d o n b o d y wei g ht at Visit 2.  
D ue t o C O VI D -1 9  p u blic healt h c o ntr ol meas ures, s o me cli nic visits ma y be s u bstit ute d wit h a c o m bi nati o n of tele me dici ne (a p h o ne call t o ca p t ure a n y a d verse 
e v e nts, c o nc o mita nt me dicati o n i nf or mati o n, a n d t o pr o vi de g ui da nce t o t he patie nt) a n d visits fr o m a h o me-healt h n urse (f or bl o o d sa m ple c ollecti o n).  
 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 1 6 /7 8  
C O N FI D E N T I A L  
2  
I N T R O D U C TI O N 
Dasi gl uca g o n is a pe pti d e a nal o g of h u ma n gl u ca g o n. Dasi gl uca g o n is a p pr o ve d b y t he  F o o d a n d 
Dr u g A d mi nistrati o n  (F D A ) f or t he treat me nt of s e vere h y p o gl yce mia i n pe diatric a n d a d ult 
patie nts wit h dia betes a g e d 6  years a n d a b o v e .1 
2. 1  Tri al  R ati o n ale  
Se vere h y p o gl yc e mia is a ris k i n all i n di vi d uals wit h dia betes, i n partic ular i n t h ose re q uiri n g 
i ns uli n treat me nt re gar dl ess of a ge. T h ere is a t hera pe utic nee d f or all i n di vi d uals at ris k f or 
se vere h y p o gl y ce mia t o ha ve access t o safe a n d effecti ve e mer g e nc y resc u e t hera pies s h o ul d 
s uc h a n e ve nt o cc ur. Th e prese nt trial ai ms t o assess  t he efficac y a n d s afet y of a si n gle 
s u bc uta ne o us ( S C) i njecti o n of dasi gl uca g o n ( 0. 3 m g or 0. 6 m g)  i n c hil dre n wit h t y pe 1 
dia betes  (T 1 D ) bel o w 6 y ears of a ge . T h e trial p o p ulati o n will i ncl u de c hil dre n treate d wit h S C 
i ns uli n i nf usi o n via i ns uli n p u m p  or m ulti ple dail y i njecti o ns ( M DI)  i n or der t o i ncl u de c hil dre n 
bel o w 1  year  of a g e . T o e ns ure t he bl o o d v ol u me c ollecte d i n t he pres e nt trial is wit hi n a n 
acce pt a ble perce nt a ge of t otal bl o o d v ol u me f or t he i n di vi d ual c hil d, c hil dre n m ust ha ve a b o d y 
wei g ht a b o ve 8 k g (s ee i ncl usi o n criteria S ecti o n 5. 1 ). O verall, t he eli gi bilit y criteria all o w f or 
e nr oll me nt of a trial p o p ulati o n cl osel y a p pr o xi mati n g t he ge neral p o p ulati o n of c hil dre n bel o w  
6  years of a ge  wit h T 1 D.   
2. 2  B ac k gr o u n d  
H y p o gl yce mi a  
H y p o gl yce mia i n patie nts wit h dia betes is defi ne d as e pis o des of a n a b n or mall y l o w plas ma 
gl uc ose c o nce ntrati o n. 2 H y p o gl yce mia  is a c o m mo n, u n pre dicta ble, a n d p ote ntiall y da n ger o us 
si de effect of treat me nt of dia betes mellit us wit h es peciall y i ns uli n or s ulf o n yl ureas. It is m ore 
fre q ue nt i n patie nts wit h m ore si g nifica nt  e n d o ge n o us i ns uli n deficie nc y, s u c h as occ urs i n T 1 D 
a n d a d va n ce d t y p e 2 dia b etes. Treat me nt of t y pe 2 dia betes wit h i ns uli n ca uses h y p o gl yce mia 
pr o gressi vel y a n d m ore fre q ue ntl y o ver ti me, w hereas i n T 1 D, h y p o gl yce mia is e x perie n ce d 
t hr o u g h o ut t he c o urse of esta blis he d disease. 
S y m pt o ms a n d si g ns of h y p o gl yce mia are  ofte n  n o n -s pecific. Patie nts e x p erie nci n g a 
h y p o gl yce mic e pis o de c o m m o nl y n ote s y m pt o ms s uc h as a n xiet y, s w eati n g, h u n ger, tre m ors, 
pal pitati o ns, parest hesia, na usea , a n d p all or. De p e n di n g o n t he se verit y, h y p o gl yce mia ma y lea d 
t o a ra n ge of s y m pt o ms fr o m mil d  co nf usi o n  t o m ore se ver e s y m pt o ms s uc h as be ha vi or al 
c ha n ges, l oss of c o ns ci o us ness, seiz ures, c o ma, a n d deat h. 1 
T he occ urre n ce  of h y p o gl yce mic e ve nts or e ve n t h e fear of h y p o gl yce mia ma y i nfl ue nce  
a d here n ce t o pr escri b e d treat me nt r e gi me ns f or di a betes. T his ca n c o ntri b ute t o s u b o pti mal  
gl yce mic c o ntr ol, w hic h i n t ur n ma y lea d t o a n i ncrease d ris k of c o m plicati o ns  of dia betes . 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 1 7 /7 8  
C O N FI D E N T I A L  
Gl uc a g o n  
Gl uca g o n is a nat ur all y occ urri n g h or m o n e, secret e d fr o m t he al p h a cells of t he pa ncreatic islets. 
Gl uca g o n pla ys a ce ntr al r ole i n t he re g ulati o n of gl uc ose h o me ostasis a n d is a ke y c o u nter  
re g ulat or y h or m o ne –  c o u nteracti n g t he effect of  i ns uli n o n bl o o d gl uc ose le vels. Gl uca g o n 
sti m ulates he patic gl yc o ge n ol ysis a n d gl uc o ne o ge nesis, t here b y raisi n g bl o o d gl uc ose  es peciall y 
d uri n g peri o ds of h y p o gl yce mia . Gl uca g o n rece pt or a g o nis m has als o bee n s h o w n t o e xert effects 
o n li pi d meta b olis m, e ner g y bala nce, b o d y a di p ose tiss ue mass , a n d f o o d i nta ke.  
I ns uli n-i n d uc e d h y p o gl yce mia ca n be re verse d b y gl uca g o n  a d mi nistrati o n . T heref ore, gl uca g o n 
is i n dicate d f or t he tr eat me nt of se vere h y p o gl yce mia. 
D asi gl uc a g o n  
Dasi gl uca g o n  is a sta ble pe pti de a nal o g of h u ma n gl uca g o n, a vaila bl e i n a rea d y-t o-use li q ui d 
f or m ulati o n a n d is a p pr o ve d b y F D A f or t he treat me nt of se vere h y p o gl yce mia i n pe diatric a n d 
a d ult patie nts wit h dia betes a ge d 6  years a n d a b o v e . Dasi gl uca g o n is a s p ecific a nd f ull gl uca g o n 
rece pt or a g o nist desi g ne d t o mi mic t he effects of gl uca g o n, ha vi n g a fast a bs or pti o n a n d 
eli mi nati o n. It is a pe pti d e of 2 9  a mi n o aci ds, wit h 7  a mi n o aci d s u bstit uti o ns c o m pare d t o nati ve 
gl uca g o n. T he mai n p ur p ose of t he s u bstit uti o ns is t o i ncrease t h e p h ysical a n d c he mical sta bilit y 
of t he gl uca g o n a n al o g c o m pare d t o mar kete d gl u ca g o n pr o d ucts s u c h as Lill y´s Gl uca g o n or 
Gl uca Ge n ® . D asi gl uca g o n e x hi bits i m pr o ve d p h ysical a n d c h e mical sta bilit y a n d is a vaila ble i n 
a n a q ue o us s ol uti o n at ne utral p H. 3 
T he cli nical de v el o p me nt pr o gra m t o s u p p ort t he i n dicati o n of treat me nt of se vere h y p o gl y ce mia 
c o m prises 3  P hase  1 trials, 1  P hase  2 trial a n d 5  P hase  3 trials. All trials ha ve bee n c o m plete d. 
T he mai n trials f or de m o nstrati o n of efficac y c o m prise 2  place b o -c o ntr olle d trials i n a d ult 
patie nts wit h T 1 D a n d a place b o -c o ntr olle d trial i n pe diatric patie nts wit h T 1 D. T he a d diti o nal 
trials c o m prise 2  i nitial P hase  1 trials, a d ose -fi n di n g trial, a de dicat e d i m m u n o ge nicit y trial, a n 
i ntra ve n o us (I V)/ Q Tc tri al, a n d a bri d gi n g trial c o m pari n g 2  dasi gl uca g o n batc hes.  
T he p har mac o ki netic ( P K ) pr ofile of 0. 6  m g d asi gl uca g o n (t he d ose l e vel teste d  i n P hase 3 trials) 
was c haract erize d b y a ra pi d i ncrease i n plas ma l e vels f oll o wi n g S C a d mi nistrati o n, wit h a 
me dia n T ma x  of a p pr o xi matel y 3 5  mi n utes (ra n ge 3 0 t o 4 5  mi n utes acr oss trials) i n a d ults a n d 
2 1  mi n utes i n pe diatric patie nts. Ma xi m u m plas ma c o n ce ntrati o n a n d t otal e x p os ure a p p eare d 
hi g her i n a d ult vers us pe diatric patie nts. Of n ote f or a ge s u b gr o u ps of t he p e diatric p o p ulati o n, 
area u n d er t he pl as ma c o nce ntrati o n vers us ti me c ur ve ( A U C ) a n d ma xi m u m o bser ve d 
c o nce ntr ati o n ( C ma x ) val ues i n c hil dre n ( 6 t o 1 1  years  of a g e ) were hi g her t ha n i n a d olesce nts 
(1 2  t o 1 7 years  of a ge ) a n d b ot h were cl os e t o t he ra n ges o bser v e d i n t he trials i n a d ult patie nts. 
T he a b o ve P K differe nces bet wee n a d ult a n d p e di atric patie nts di d n ot tra nslate i nt o differe n ces 
i n efficac y bet w ee n t he t w o p o p ulati o ns.3 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 1 8 /7 8  
C O N FI D E N T I A L  
2. 3  Be nefit/ Ris k Ass ess m e nt  
Gl uca g o n res c ue t hera pies i ncl u di n g gl uca g o n e mer ge nc y kits are u n der uti lize d i n t he treat me nt 
of patie nts w h o e x perie n ce se vere h y p o gl yce mia. C o nsi deri n g t he seri o us ness a n d p ote ntial 
c o m plicati o ns t hat ca n arise fr o m se vere h y p o gl yce mic e ve nts , it is esse ntial t hat all patie nts at 
ris k f or se vere h y p o gl yc e mia are prescri b e d res c ue t hera p y a n d t hat t heir care gi vers recei ve 
a de q uate, h a n ds -o n  trai ni n g f or use of gl uca g o n resc ue treat me nts t o e ns ure safe, ti mel y, a n d 
effecti ve a d mi nistrati o n. Gi ve n t he c halle n g es wit h p are nt/care gi ver trai ni n g a n d use of gl uca g o n 
kits f or rec o nstit uti o n, Zeala n d P har ma A/ S has de vel o pe d  dasi gl uca g o n as a rea d y -t o-use resc u e 
treat me nt f or s e vere h y p o gl yce mia. T he de v el o p me nt of dasi gl uca g o n pr o vi des pare nts a n d 
care gi v ers of c hil dre n wit h  dia betes mellit us a si m pler alter nati ve t o resc u e kits f or t he treat me nt 
of se vere h y p o gl yce mia. T he rea d y -t o-use pr o d uct a d dresses a n u n met nee d a n d ma y p ote ntiall y 
pr o ve t o be lifesa vi n g. 
As gl uca g o n a n d its a nal o gs bel o n g t o a well -k n o w n dr u g class wit h a k n o w n m o de of acti o n, 
dasi gl uca g o n is n ot e x pecte d t o be a hi g h -ris k m olec ule. 
Treat me nt wit h a n i n vesti gati o nal me dici nal pr o d uct  (I M P) ma y res ult i n u n desire d effects or 
c o m plai nts. U n desire d effects a n d c o m plai nts s uc h as na usea a n d v o miti n g are k n o w n a d verse 
e ve nts (A Es ) o cc urri n g wit h gl uca g o n a d mi nistrati o n. Si milar A Es ha ve als o bee n o bser ve d i n 
t he 9  cli nical st u dies c o n d ucte d wit h  dasi gl uca g o n. As wit h e ver y i n vesti gati o nal t hera p y, ne w 
a n d yet u n k n o w n si de effects als o ma y occ ur.  
T here are li mite d data a v aila ble t o assess t he i m m u n o ge nic p ote ntial of gl u ca g o n pr o d ucts 
a vaila ble o n t he mar ket, b ut t he data a vaila ble i n dicate t hat m ar kete d gl uca g o n o nl y has a s mall  
i m m u n o ge nic p ote ntial. I m m u n o ge nic p ote ntial has bee n i n vesti gate d i n t he cli nical de vel o p me nt 
pr o gra m t o s u p p ort t he i n dicati o n of treat me nt of s e vere h y p o gl y ce mia. I n t he cli nical trials f or 
t his i n dicati o n, 4/ 4 9 8 ( < 1 %) of dasi gl uca g o n treat e d patie nts de vel o pe d treat me nt -e mer g e nt 
a nti-dr u g a nti b o dies ( A D As). F or i m m u n o ge nic p ote ntial i n ot her i n dicati o ns wit h c hr o nic 
dasi gl uca g o n treat me nt, r efer t o t he I B f or dasi gl u ca g o n. 3 
A d mi nistrati o n of dasi gl uca g o n ma y be ass ociate d wit h a ris k of aller gic reacti o ns si milar t o 
t h ose o bser ve d f or ot her t hera pe utic p e pti des or pr otei ns. Patie nts wit h k n o w n or s us pecte d 
aller gies t o t he I M P or relate d pr o d ucts will be e x cl u de d fr o m t he trial. Mil d or m o derate aller gic 
reacti o ns ma y i ncl u d e s y m pt o ms of ras h, fe ver, fl u-li ke s y m pt o ms, na usea, hea dac he, a n d 
m yal gia. Ac ute ge n eralize d h y perse nsiti vit y reacti o ns are us uall y ver y rare b ut ma y i ncl u de 
s y m pt o ms of fl us hi n g, s weati n g, dizzi ness, c ha n g e i n bl o o d press ure a n d diffic ulties i n breat hi n g. 
N o se vere ac ut e h y pers e nsiti vit y reacti o ns ha ve b ee n o bser ve d i n t he 9  cli nical trials c o n d ucte d 
wit h dasi gl uca g o n. Direct access t o res uscitati o n e q ui p m e nt is e ns ure d at t he cli nical trial sites. 
Wit h t he e xce pti o n of me dical e xa mi nati o ns, a pati e nt partici pati n g i n t his trial is n ot li kel y t o 
deri ve a n y p ers o nal he alt h -relate d b e nefits. T he res ults of t he trial ma y c o ntri b ute t o t he f ut ure 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 1 9 /7 8  
C O N FI D E N T I A L  
use of dasi gl u ca g o n i n patie nts wit h dia betes mellit us e x perie nci n g se v ere h y p o gl yce mic 
reacti o ns. 
O verall, t he be n efit t o ris k rati o f or patie nts e nt eri n g t he Z P 4 2 0 7 -2 1 0 5 2  trial is c o nsi dere d 
acce pta ble.  
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 E s of dasi gl uca g o n  ma y be f o u n d i n t he I n v esti gat or’s Br oc h ure (I B )3 a n d t he 
Ze gal o g ue ®  la bel.1 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 2 0 /7 8  
C O N FI D E N T I A L  
3  
O B J E C TI V E S A N D E N D P OI N T S  
 
O bjecti ves  
E n d p oi nts  
T o assess t he efficac y of 
dasi gl uca g o n i njecti o n i n 
c hil dre n <  6  years of a ge  wit h 
T 1 D  
Pri mar y e n d p oi nt  is p har mac o d y na mics ( P D): 
Plas ma gl uc ose c ha n ge fr o m baseli ne at 3 0  mi n utes after I M P i njecti o n 
or at t he ti me of resc ue b y I V gl uc ose  
Sec o n dar y e n d p oi nt  is P D* : 
Plas ma gl uc ose c ha n ge fr o m baseli ne at 1 5  mi n utes after I M P i njecti o n 
or at t he ti me of resc ue b y I V gl uc ose  
T o assess P K of dasi gl uca g o n 
i n c hil dre n wit h T 1 D 
P K e n d p oi nts will be deri ve d fr o m plas ma dasi gl uca g o n pr ofiles fr o m 
0 t o 3 0 0  mi n utes * : 
•  
Area u n der t he plas ma c o nce ntrati o n vers us ti me c ur ve fr o m 0 
t o 3 0 mi n utes p ost -d ose  ( A U C0 -3 0 mi n) 
•  
A U C fr o m 0 t o 3 0 0 mi n utes p ost -d ose  ( A U C0 -3 0 0 mi n) 
•  
A U C fr o m 0 t o t he last ti me p oi nt wit h a meas ure d 
c o nce ntrati o n ( A U C 0 -t) 
•  
A U C fr o m 0 t o i nfi nit y p ost -d ose ( A U C i nf) 
•  
C ma x  
•  
Ti me t o C ma x   
•  
T ma x  
•  
Ter mi nal eli mi nati o n rate c o nsta nt of plas ma dasi gl uca g o n ( λ z) 
•  
Ter mi nal plas ma eli mi nati o n half -life of dasi gl uca g o n (t½ ) 
•  
T otal b o d y cleara nce of plas ma dasi gl uca g o n ( Cl/f)  
•  
V ol u me of distri b uti o n of plas ma dasi gl uca g o n ( Vz/f) 
•  Mea n resi de nce ti me of plas ma dasi gl uca g o n ( M R T)  
T o assess t he safet y pr ofile of 
dasi gl uca g o n i n c hil dre n wit h 
T 1 D  
•  
A E s 
•  
A d mi nistrati o n of resc ue I V gl uc ose i nf usi o n wit hi n 
3 0  mi n utes of I M P i njecti o n  
•  
Ti me t o first I V gl uc ose i nf usi o n f oll o wi n g treat me nt wit h 
dasi gl uca g o n wit hi n 3 0  mi n utes  
 
Ot her e n d p oi nts  
•  
A nti -dr u g a nti b o dies  
A b bre viati o ns: A D A =a nti -dr u g a nti b o dies; A E =a d verse e ve nt; A U C = plas ma c o nce ntrati o n vers us ti me c ur ve; 
I M P =i n vesti gati o nal me dici nal pr o d uct; I V =i ntra ve n o us; P D = p har mac o d y na mics; P K = p har mac o ki netics; 
T 1 D = T y pe  1 dia betes  
* as t he sa m pli n g fre q ue nc y f or P K  a n d P D will gra d uall y be re d uce d wit h l o wer wei g ht f or c hil dre n of 1 0 k g a n d 
bel o w (as s pecifie d i n Ta ble  6 -4 ), t hese mar ke d e n d p oi nts will be assesse d t o t he e xte nt p ossi ble base d o n t he 
sa m ples o btai ne d f or t he i n di vi d ual c hil d. 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 2 1 /7 8  
C O N FI D E N T I A L  
4  
T RI A L  D E SI G N  
4. 1  O ver all Desi g n  
T his trial will use a  si n gle-a d mi nistrati o n , o pe n-la bel trial desi g n t o assess t he a bilit y of a si n gle 
S C i njecti o n of dasi gl uca g o n t o i ncrease pl as ma gl uc ose i n pe diatric c hil dre n wit h T 1 D wit h 
h y p o gl yce mia . A t otal of 8  c hil dre n will be i n cl u d e d; 4 c hil dre n recei vi n g a d ose of 0. 3 m g a n d 
4  c hil dre n recei vi n g a d ose of 0. 6 m g. Of t he 4 c hil dre n recei vi n g 0. 3 m g , 2 c hil dre n s h o ul d 
prefera bl y  be b el o w 2 years at scree ni n g. T he  re m ai ni n g 2 c hil dre n a ge d 2 years or a b o ve  
recei vi n g 0. 3 m g s h o ul d prefera bl y  be b el o w 4 years  at scree ni n g . F or c hil dre n recei vi n g t he 
0. 6  m g d ose, all m ust be a b o ve 2 years at scree ni n g. Bef ore a n eli gi ble c hil d is d ose d, t he d ose 
le vel ( 0. 6 m g or 0. 3  m g) m ust be c o nfir me d b y t he sp o ns or. Eac h c hil d will be d ose d aft er t he 
safet y assess me nt of t he prece di n g c hil d has  bee n c o m plete d a n d ass esse d b y t he Trial Safet y 
Gr o u p . 
T he trial will i ncl u de t he f oll o wi n g visits (as ill ustrate d i n Fi g ur e  4 -1 ). 
•  A scree ni n g visit ( Visit 1, pre -treat me nt visit) i n t he peri o d fr o m Da y ‑ 5 0 t o Da y ‑ 2 9 
•  A d osi n g visit  ( Visit 2), Da y 1 ( da y of si n gle d osi n g wit h I M P) 
•  A Safet y  f oll o w-u p visit ( Visit 3) at Da y 2 9  + 5  d a ys (t he e n d -of -trial visit) 
T he p ri mar y e n d p oi nt of t he trial is plas ma gl uc ose c ha n g e fr o m bas eli ne at 3 0 mi n utes after I M P 
i njecti o n or at t he ti me of resc ue b y I V gl uc ose . P h ar mac o d y n a mics ( P D) i.e., p las ma gl ucose 
will be assesse d at bas eli ne  a n d 1 5 a n d 3 0  mi n utes after d osi n g , w hile t he gl uc ose le vels will be 
m o nit ore d b y C G M a n d b y a plas ma gl uc ose a nal yzer  d uri n g t he d osi n g visit  ( Visit 2) . P K will 
be assesse d t hr o u g h o ut a 3 0 0 -mi n ute peri o d at t he d osi n g visit  ( Visit 2) . Safet y will be assesse d 
pri or t o d osi n g a n d t hr o u g h o ut a 3 0 0 -mi n ute peri o d after d osi n g a n d a gai n at t he f oll o w -u p visit.  
All data m ust be l o g ge d i n t he electr o nic case re p ort f or m ( e C R F ). 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 2 2 /7 8  
C O N FI D E N T I A L  
Fi g ure  4 -1  
Tri al D esi g n  
 
 
4. 2  Scie ntific R ati o n ale f o r Tri al  Desi g n  
T his is a P hase  3, si n gle-a d mi nistrati o n  o pe n -la bel trial t o assess t he efficac y, safet y, P K a n d P D 
of dasi gl uca g o n w h e n a d mi nistere d as a resc ue t h era p y f or h y p o gl yce mia i n c hil dre n bel o w 
6  years  of a ge wit h T 1 D. A place b o tr eat me nt ar m was o mi tte d t o a v oi d u n necessar y l o n g 
d urati o n of h y p o gl yce mi a i n t his v ul nera ble a g e gr o u p.  
I n t he prese nt tri al, c hil dre n  wit h T 1 D are select e d base d o n t he rati o nale descri be d i n 
Secti o n  2. 1 . T he n u m ber of c hil dre n i n t he trial is n ot base d o n a f or mal sa m ple size calc ul ati o n. 
C o nsi deri n g t he l o wer i n ci de nce a n d pre v ale nce of T 1 D i n t his a ge gr o u p, t y pe of i n dicati o n, a n d 
h ealt h aut h orities’  fee d bac k, 8 c hil dre n are b elie ve d t o be a p pr o priat e t o ass ess efficac y a n d 
safet y. 
4. 3  J ustific ati o n f or D ose  
Dasi gl uca g o n  b ol us d ose of 0. 6  m g  S C  has bee n  a p pr o ve d b y F D A f or t h e treat me nt of se v ere 
h y p o gl yce mia i n pe diatri c a n d a d ult patie nts wit h dia betes a ge d 6  y ears a n d a b o ve . Base d o n 
p o p ulati o n P K m o del pre dicti o ns  a n d P o p P K/ P D Si m ulati o ns  ( St u d y 2 0-0 4 6) , th e 0. 6 m g d ose is 
e x pecte d t o b e a n a p pr o pri ate d ose i n an  ol der s u bset of c hil dre n <  6  y ears a n d ≥ 2 years , 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 2 3 /7 8  
C O N FI D E N T I A L  
w hereas a l o wer d ose of 0. 3 m g is e x pecte d t o be a n a p pr o pri ate d ose i n a y o u n ger s u bset of 
c hil dre n <  6 years . T h e res ults fr o m t he prese nt tri al will be use d t o deter mi ne t he a p pr o priate 
d ose (s) f or c hil dre n < 6 y ears. 
T he rati o nale f or t he s u g geste d s plit i n d oses bet wee n t he 2 gr o u ps , w hi c h are partiall y 
o verla p pi n g, is  t o ma xi mize t he efficac y be nefit i n t his v ul nera ble a ge gr o u p wit h o ut a n y 
i ncreas e i n u nt o war d effects. Y o u n g c hil dre n are m ore s usce pti ble t o l o w bl o o d gl uc ose a n d i n 
a d diti o n t o t his, it has bee n s h o w n t hat t he fre q ue nc y of se vere h y p o gl yce mia is o ne of  t he 
fact ors t hat has a ne g ati ve i m pact o n s pecifi c ne ur o ps yc h ol o gical f u ncti o ns. 
4. 3. 1  P h ar m ac o ki netics  
I n t he p o p ulati o n P K re p ort 1 9-0 7 7 ,4 2 m o dels were de vel o p e d t o c o ver c hil dre n bel o w 6  years 
of a ge: t he fi n al p o p ulati o n P K m o del a n d a n alter nati ve p o p ulati o n P K m o del. T he fi nal m o del 
s h o we d a piece-wis e li near rel ati o ns hi p bet wee n a ge a n d rel ati ve bi oa vaila bilit y. T he alter nati ve 
m o del ass u me d a trial effect of bi oa vaila bilit y f or t he pe diatric trial Z P 4 2 0 7 -1 7 0 8 6 (a ge 6 t o 
1 7  years) v ers us a d ults b ut was less r o b ust t ha n t he fi nal m o del. T he P o p P K/ P D Si m ulati o ns 
( St u d y 2 0-0 4 6) use d t he P o p  P D m o del a n d b ot h P K m o dels.  
C hil dre n < 6 ye ars a n d ≥ 2 ye ars : j ustific ati o n f or 0. 6 m g d ose  
T he fi nal P o p P K m o del ( St u d y 1 9 -0 7 7) s h o we d a mea n C ma x  a n d A U C t hat was 1. 9  a n d 
1. 5  ti mes hi g her i n 2 - t o 3 -year -ol d s wit h a 0. 6 m g d ose c o m pare d t o t he e x p os ure i n a d ults wit h 
0. 6  m g , res pecti vel y. T he alter nati ve m o del i n dicat e d t hese val ues t o b e 4. 5  a n d 3. 7  ti mes hi g her 
c o m pare d t o a d ults. T he s pa n of P K pre dicti o ns b ase d o n t he fi nal a n d alter nati ve P K m o dels ca n 
be see n as a p ossi ble realistic ra n ge.  
C hil dre n prefer a bl y < 4 ye ars : j ustific ati o n f or 0. 3 m g d ose  
T he fi nal P o p  P K m o del ( St u d y 1 9 -0 7 7) s h o we d a mea n C ma x  a n d A U C t hat was  1. 4 a n d 
1. 1  ti mes hi g her i n 0- t o 1-year -ol ds f or a d os e of 0. 3 m g c o m pare d t o t he e x p os ure i n a d ults wit h 
0. 6  m g, res pecti vel y. T he rati o was 0. 9  a n d 0.7  f or Cma x  a n d A U C i n 3 - t o 4 -year -ol ds f or a d os e 
of 0. 3 m g c o m pare d t o t h e e x p os ure i n a d ults wit h 0. 6 m g, res pecti vel y.  
T he alter nati ve m o del i n dicate d t hese v al ues  f or Cma x  a n d A U C  t o be 4. 0 a n d 3. 1 ti mes hi g her i n 
0 - t o 1-year -ol ds a n d 2. 0  a n d 1. 7  ti mes hi g her i n 3 - t o 4 -year -ol ds c o m pare d t o a d ults. T he s pa n 
of P K pre dicti o ns base d o n t he fi nal a n d alter nati ve P K m o dels ca n be s ee n as a p ossi ble realistic 
ra n ge. 
4. 3. 2  C ar di ac re p ol ariz ati o n a n d d asi gl uc a g o n c o nce ntr ati o n  
T o assess t he effect of dasi gl uca g o n o n car di ac re p olarizati o n, trial Z P 4 2 0 7 -1 7 1 4 4 was 
c o n d ucte d i n a d ult healt h y v ol u nteers t o i n vesti gate t he effect of I V dasi gl u ca g o n u p t o 1. 5  m g 
o n electr ocar di o gra m ( E C G) para met ers. Dasi gl u ca g o n s h o we d n o cli nicall y rele va nt effects o n 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 2 4 /7 8  
C O N FI D E N T I A L  
st u die d E C G para meters a n d a n effect of dasi gl uca g o n o n c orrecte d Q T pr ol o n gati o n e xcee di n g 
1 0  ms was e xcl u de d wit hi n t he o bser ve d c o n ce ntr ati o n ra n ge u p t o ~ 3 0, 0 0 0  p m ol/ L.  
C hil dre n < 6 ye ars a n d ≥ 2 ye ars : justific ati o n f or 0. 6 m g d ose  
Si nce t he pre dicte d C ma x  fr o m b ot h P K m o dels ( 0. 6 m g d ose: fi nal m o del: 1, 2 3 0 t o 4, 2 4 0  p m ol/ L 
i n c hil dre n a ge d 2 t o 3 years a n d alter nati ve m o del: 3, 0 9 0 t o 1 0, 5 0 0  p m ol/ L i n c hil dre n a ge d 2 t o 
3  years) is s u bsta ntiall y l o wer  (at least 2. 9 ti mes l o wer) t ha n t h e o bser ve d c o nce ntr ati o n ra n ge, 
t he use of 0. 6  m g dasi gl uca g o n is c o nsi dere d t o be safe i n c hil dre n < 6 years a n d ≥ 2 years  wit h 
re gar ds t o t he ris k of Q T pr ol o n gati o n. 
C hil dre n prefer a bl y < 4 ye ars: j ustific ati o n f or 0. 3 m g d ose  
Si nce t he pre dicte d C ma x  fr o m b ot h P K m o dels ( 0. 3 m g d ose: fi nal m o del: 9 2 6 t o 3, 6 6 0  p m ol/ L i n 
c hil dre n a ge d 0 t o 1  y ears a n d alter nati ve m o d el: 2, 6 0 0 t o 1 0, 5 0 0  p m ol/ L i n c hil dre n a ge d 0 t o 
1  years) is s u bsta ntiall y l o wer (at least 2. 9 ti mes l o wer) t ha n t h e o bser ve d c o nce ntr ati o n ra n ge, 
t he use of 0. 3 m g dasi gl uca g o n is c o nsi dere d t o be safe wit h re g ar ds t o t he ris k of Q T 
pr ol o n gati o n.  
4. 3. 3  S afet y  
O verall, t he safet y pr ofil e f or dasi gl uca g o n, as det er mi ne d fr o m t he c o m pl ete d de vel o p me nt 
pr o gra m f or tr eat me nt of se vere h y p o gl y ce mia i n a d ults a n d pe diatric patie nt s a ge d ≥ 6 t o 
≤ 1 7  years  wit h a d ose of 0. 6  m g , is c o nsiste nt wit h t he well-k n o w n class effects ass oci ate d wit h 
gl uca g o n rece pt or a g o nis m. T he m ost fre q ue ntl y re p orte d A E s w ere n a usea a n d v o miti n g, w hic h 
are k n o w n si de effects f oll o wi n g a d mi nistrati o n of gl uca g o n.  
I n t he p e diatric tri al Z P 4 2 0 7-1 7 0 8 6 , a hi g her fre q ue nc y of gastr oi ntesti nal  e ve nts was see n i n 
a d olesce nts t ha n i n patie nt s 7 t o 1 1  years of a g e  a n d n o ass ociati o n bet wee n na usea/ v o miti n g a n d 
e x p os ure ( C ma x  a n d A U C) was dete cte d. I n t he 4  trials i n t he de vel o p me nt pr o gra m w here a ra n g e 
of das i gl uca g o n d oses w as teste d i n a d ults, na usea a n d v o miti n g were pri maril y re p orte d wit h 
d oses of 0. 3  m g or hi g her. T he re p ort e d na usea a n d v o miti n g were mil d or m o derate a n d 
tra nsie nt. Na usea a n d v o miti n g a p peare d at a si milar fre q u e nc y t o mar kete d gl uca g o n i n t he 
pi v otal trials i n a d ults. A part fr o m na us ea a n d v o miti n g ( gastr oi ntesti nal A Es), t here was n o 
a p pare nt relati o ns hi p bet wee n dasi gl uca g o n d ose a n d t he fre q ue nc y of A Es i n a n y of t he trials 
w here a ra n g e of d oses u p t o 2  m g S C dasi gl uca g o n was teste d . 
A si n gle seri o us A E  ( S A E) (a n e v e nt of h y p o gl yce mia i n a n a d ult, w hic h was dee me d u nrelat e d 
t o i n vesti gati o nal pr o d uct treat me nt) was re p ort e d i n t he c o m plete d de vel o p me nt pr o gra m, a n d 
m ost A Es were e v e nts of mil d or m o derate se verit y. A nti b o d y f or mati o n was o bser ve d i n less 
t ha n 1 % of patie nt s e x p ose d t o dasi gl uca g o n ( 4/ 4 9 8 pat ie nts), a n d n o i m m u n o ge nicit y-relate d 
A Es were i de ntifie d f or a n y of t he patie nt s w h o ha d  a nti-dasi gl uca g o n a nti b o dies ( 3  a d ults a n d 
1  c hil d). 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 2 5 /7 8  
C O N FI D E N T I A L  
Ta ke n t o get her, ra pi d r ec o ver y is hi g hl y warra nte d i n ver y y o u n g c hil dre n d ue t o t he i ncrease d 
s usce pti bilit y a n d detri me ntal effects of se v ere h y p o gl yce mia i n t his a ge gr o u p. Base d o n cli nical 
data, n o i ncrease d safet y ris ks are e x p ecte d w he n d osi n g c hil dre n <  6  years a n d ≥ 2 years  wit h 
0. 6  m g dasi gl uca g o n a n d c hil dre n prefera bl y  bel o w 4 years  wit h 0. 3  m g dasi gl uca g o n e ve n 
t h o u g h P K si m ulati o ns pre dict a hi g her e x p os ure c o m pare d t o a d ults a n d c hil dre n ≥ 6  years. 
Gastr oi ntesti nal e ve nts s uc h as na usea a n d v o miti n g ha ve bee n re p orte d t hr o u g h o ut t he 
c o m plete d cli nical pr o gra m. I n t he c o m plete d pe di atric trial, n o rel ati o ns hi p was see n b et wee n 
dasi gl uca g o n e x p os ur e a n d t he occ urre nce of na usea a n d v o miti n g t hat  w o ul d i n dicate a n y 
i ncreas e d ris k i n y o u n ger c hil dre n. N o effect o n car diac re p olarizati o n is e x pecte d si nce t h e 
ma xi m u m pre dicte d dasi gl uca g o n c o nce ntrati o n i n y o u n g c hil dre n is s u bsta ntiall y l o wer  (at least 
2. 9 ti mes l o wer)  b ot h f or c hil dre n < 6 years a n d ≥ 2 years recei vi n g 0. 6  m g a n d c hil dre n 
prefera bl y bel o w 4 y ears recei vi n g 0. 3 m g dasi gl u ca g o n  t ha n t he dasi gl uca g o n c o nce ntr ati o n 
esta blis he d t o ha ve n o c orrect e d Q T pr ol o n gati o n e xcee di n g 1 0  m g  i n a d ults (trial Z P 4 2 0 7-
1 7 1 4 4) . 
4. 4  E n d -of -T ri al  Defi niti o n  
T he e n d of t he tri al is defi ne d as t he date of t he last visit of t he last patie nt  i n t he trial. 
A patie nt  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 all p hases of t he trial 
i ncl u di n g t he last f oll o w-u p  visit  ( Visit 3) . 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 2 6 /7 8  
C O N FI D E N T I A L  
5  
T R I A L P O P U L A TI 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 eli gibilit y  criteria, als o k n o w n as 
pr ot oc ol wai vers or e xe m pti o ns, are n ot per mitte d.  
5. 1  I ncl usi o n Criteri a 
C hil dre n  are eli gi ble t o b e e nr olle d i n t he trial o nl y if all of t he f oll o wi n g criteria a p pl y:  
A ge  
1.  C hil d m ust b e <  6  years at t he ti me of scree ni n g.  
T y pe of P atie nt  a n d Dise ase C h ar acteristi cs  
2.  C hil dre n  w h o are c o nfir me d as ha vi n g T 1 D  bas e d o n me dical hist or y a n d are recei vi n g 
dail y i ns uli n t hera p y via i ns uli n p u m p or M DI . 
I nf or me d C o nse nt 
3.  F oll o wi n g recei pt of ver bal a n d writte n i nf or mati o n a b o ut t he trial, t he pare nt (s) or le gal 
g uar dia n  of t he c hil d m ust be c a pa bl e of gi vi n g si g ne d i nf or me d c o ns e nt  bef ore a n y trial -
relate d acti vit y is carrie d o ut as descri be d i n A p pe n di x  1  w hic h i ncl u des c o m plia nce wit h 
t he re q uire m e nts a n d restricti o ns liste d i n t he i nf or me d c o nse nt f or m (I C F) a n d i n t his 
pr ot oc ol.  
4.  A bilit y t o a d here t o t he pr ot oc ol re q uire m e nts . 
Wei g ht  
5.  B o d y wei g ht > 8 k g . 
 
5. 2  E xcl usi o n Criteri a  
Patie nt s 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: 
Me dic al C o n diti o ns  
1.  K n o w n or s us pect e d aller g y t o t he I M P or relate d pr o d ucts  
2.  A n y c o n diti o n t hat i n t he i n vesti gat ors o pi ni o n  ma y res ult i n di mi nis he d he patic gl yc o ge n 
st ores (e g, pr ol o n g e d fasti n g ( m ore t ha n 2 4 h o urs)  at V isit 2  
3.  Hist or y of a na p h yla xis or s y m pt o ms of se vere s yst e mic aller g y (s u c h as a n gi oe de ma)  
4.  Hist or y of a n y h y p o gl yce mic e ve nt  i n dicati n g trial pr oce d ures t o be hi g h ris k f or t he 
c hil d, as j u d ge d b y t he i n vesti gat or  
5.  Hist or y of se vere h y p o gl yce mic e v e nt ( defi ne d as a n e ve nt ass o ciate d wit h a seiz ure or 
l oss of c o nsci o us ness or re q uiri n g e mer g e nc y me di cal pers o n n el, a visit t o t he e mer g e nc y 
de part me nt, or a h os pital a d missi o n) wit hi n 3  m o nt hs pri or t o scree ni n g  
6.  Hist or y of e pile ps y or sei z ure dis or der  
7.  Acti v e mali g na nc y  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 2 7 /7 8  
C O N FI D E N T I A L  
8.  C o n ge nital heart diseas e  
9.  C urre nt blee di n g dis or der, i ncl u di n g a nti -c oa g ula nt treat me nt  
1 0.  K n o w n prese n ce or hist or y of p he oc hr o m oc yt o ma (ie , a dre nal gla n d t u m or) or 
i ns uli n o ma (ie, i ns uli n secreti n g pa ncreas t u m or) 
1 1.  S ur ger y or tra u m a wit h si g nifica nt bl o o d l oss wit hi n t he last 2  m o nt hs pri or t o scree ni n g  
Pri or/ C o nc o mit a nt T her a p y  
1 2.  Use of dail y s yste mic bet a -bl oc ker, i n d o met haci n, warfari n, or a ntic h oli ner gic dr u gs  
1 3.  U se of prescri pti o n or n o n -prescri pti o n me dicati o ns k n o w n t o ca use Q T pr ol o n gati o n  
Pri or/ C o nc urre nt Cli nic al Tri al  E x perie nce  
1 4.  Pre vi o us partici pati o n i n t his trial. Partici pati o n is defi ne d as recei ve d treat me nt wit h I M P  
1 5.  Recei pt of a n y i n vesti gati o nal dr u g wit hi n 3  m o nt hs pri o r t o scree ni n g 
Di a g n ostic A ssess me nts 
1 6.  As partate a mi n otra nsferase ( A S T) or ala ni ne a mi n otra nsferase ( A L T) > 2. 5 × t he u p per 
li mit of t he n or mal ra n ge ( U L N) 
1 7.  E sti mate d gl o mer ular filtrati o n rate < 3 0 m L/ mi n/ 1. 7 3  m 2 acc or di n g t o t he M o dificati o n 
of Diet i n Re nal Diseas e st u d y defi niti o n  
1 8.  A ltere d ele ctr ol yte val ues of cli nical rele va nce f or car diac c o n d ucti o n, as j u d ge d b y t he 
i n vesti gat or 
1 9.  Cli nicall y si g nifica nt a b n or mal E C G at scree ni n g as j u d ge d b y t he i n vesti gat or  
2 0.  C li nicall y si g nifica nt ill ness wit hi n 4 wee ks bef ore scree ni n g, as j u d ge d b y t he 
i n vesti gat or 
Ot her E xcl usi o ns  
2 1.  A n y c o n diti o n t hat mi g ht je o par dize t h e c hil d’s safet y or c o m plia nce wit h t he pr ot oc ol as 
j u d ge d b y t he i n vesti gat or 
5. 3  Lifest yle C o nsi de r ati o ns  
5. 3. 1  Me al s a n d Diet ar y Restricti o ns ( Visit 2)  
1.  C hil dre n  will n ot be all o we d t o eat or dri n k (e xce pt water) fr o m 4  h o ur s bef ore d osi n g 
u ntil 3 5  mi n utes after dasi gl uca g o n a d mi nistrati o n . 
2.  3 5  mi n utes after d osi n g,  c hil dre n will be all o we d t o eat a n d dri n k m o deratel y (a p pr o priat e 
t o t heir b o d y size, wit h a ma xi m u m of 5 0 gr a ms  car b o h y drates) t o mi ni mize disc o mf ort 
i n ter ms of p ote ntial na us ea. 2  h o urs  after d osi n g , c hil dre n ca n eat a n d dri n k t heir us ual 
meals.  T he a m o u nt a n d t y pe of f o o d a n d dri n k c o ns u me d wi ll be rec or de d. 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 2 8 /7 8  
C O N FI D E N T I A L  
5. 3. 2  Acti vit y  
3.  C hil dre n  s h o ul d re mai n i n be d, t o t he e xte nt p ossi ble, fr o m a p pr o xi matel y 3 0 mi n utes 
bef ore h y p o gl y ce mia i n d ucti o n  u ntil c o m pleti o n of t he test pr oce d ure 3 0 0  mi n utes after 
d osi n g ( bat hr o o m visits are all o we d).  
5. 4  Scree n F ail ures  
Scree n fail ures are defi ne d as patie nt s w h o c o nse nt t o partici pate i n t he cli ni cal trial b ut are n ot 
s u bse q ue ntl y eli gi ble f or t he trial. 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 ure patie nt s t o meet t he C o ns oli date d Sta n dar ds of 
Re p orti n g Trials p u blis hi n g re q uire me nts a n d t o res p o n d t o q ueries fr o m r e g ulat or y a ut h orit ies. 
Mi ni mal i nf or mati o n i ncl u des de m o gra p h y, s cree n fail ure det ails, eli gi bilit y criteria, a n d a n y 
S A E.  T he reas o n f or scree n fail ure m ust be ca pt ur e d i n t he e C R F. 
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 (scree n fail ure) ma y be 
rescree ne d if i n vesti gat or j u d ges t hat rescree ni n g is a p pr o priate d ue t o i ncl usi o n  or e xcl usi o n 
criteria t hat ma y h a ve c h a n ge d. Rescree n i n g ma y o nl y be perf or m e d o nce . 
5. 5  Criteri a f or Te m p or a ril y Del a yi n g E nr oll m e nt  a n d  A d mi nistr ati o n  of Tri al  
I nter ve nti o n 
Eac h c hil d ma y ha v e t heir d osi n g visit resc he d ule d wit hi n t he visit wi n d o w f or Visit 2 wit h a n 
a d diti o nal 2 1 da ys c o m pare d t o Visit 1 ( t h us t he ma xi m u m ti me i nter val bet wee n Visit 1 a n d 
Visit 2 will be 5 0 da ys + 2 1 da ys ) d ue t o t he f oll o wi n g circ u msta nces:  
•  If t he patie nt has ta k e n a n y pr o hi bite d me dicati o n pri or t o t he d osi n g visit ( Visit 2)  
•  If tra nsie nt ill ness mea ns t hat t he patie nt ca n n ot  att e n d t he pla n ne d d osi n g visit  ( Visit 2) 
•  If t he patie nt c a n n ot atte n d t he pla n ne d d osi n g visit  ( Visit 2) d ue t o l o gistical reas o ns  
•  If t he tar get plas ma gl uc ose ca n n ot be ac hie ve d o n t he d osi n g da y ( Visit 2)  w hile 
i n d uci n g h y p o gl yce mia 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 2 9 /7 8  
C O N FI D E N T I A L  
6  
T RI A L  I N T E R V E N TI O N( S) A N D C O N C O MI T A N T T H E R A P Y 
Trial  i nter ve nti o n is defi ne d as a n y i n vesti gati o nal i nter ve nti o n(s), mar ket e d pr o d uct(s), or 
me dical de vice(s) i nte n d e d t o be a d mi nistere d t o a trial patie nt  acc or di n g t o t he trial pr ot oc ol.  
6. 1  Tri al  I nter ve nti o n(s) A d mi nistere d 
T he I M P of 0. 6  m g/ 0. 6  m L d asi gl uca g o n, will be s u p plie d b y t he s p o ns or a n d deli vere d i n a 
pre -fille d s yri n ge. O nl y eli gi ble c hil dre n ma y recei ve dasi gl uca g o n.  D asi gl uca g o n  will be  
pre pare d f or a d mi nistrati o n b y a desi g nate d pers o n at t he cli nical res earc h site a n d will be 
a d mi nistere d b y a ut h orize d  site staff as a S C i njecti o n i nt o t he b utt oc k s.  
T he pre -fille d s yri n ge d o es n ot ha ve a s cale. T heref ore, a d mi nistrati o n of 0. 3 m g / 0. 3 m L  
dasi gl uca g o n re q uir es a d diti o nal pre parati o n , w here da si gl uca g o n will  be tra nsferre d i nt o a 
sterile vial a n d t he v ol u me nee d e d i n or der t o a d mi nister 0. 3 m L will  be dra w n i nt o a s yri n ge . 
T he nee dle us e d f or a d mi nistrati o n will matc h t he nee dle of t he pre -fille d s yri n ge ( 2 7 G, ½ inc h) . 
Nee dle, s yri n g e , a n d vials will be s u p plie d b y Zeala n d P har ma . S e parate I nstr ucti o ns f or Use 
i ncl u de d i n t he Trial Mat erials Ma n ual will descri be pre parati o n a n d a d mi nistrati o n of t he 
0. 3  m g / 0. 3 m L d ose.  
T he I M P m ust be vis uall y i ns pecte d pri or t o a d mi nistrati o n. T he s ol u ti o n s h o ul d a p pear clear, 
c ol orless, a n d free fr o m particles. If t h e s ol uti o n is disc ol ore d or c o ntai ns p artic ulate matter, d o 
n ot use. T he d ose ( 0. 3 or 0. 6 m g) , date a n d ti me of eac h d ose a d mi nistere d will be rec or de d i n 
t he s o urce d o c u me nts. 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 3 0 /7 8  
C O N FI D E N T I A L  
T a ble  6 -1  
I de ntific ati o n of Tri al I nter ve nti o n 
 
I n vesti g ati o n al 
m e dici n al p r o d uct 
B ac k gr o u n d 
i nter ve nti o n 
C G M  
I nter ve nti o n Na me 
Dasi gl uca g o n  
A pi dra ®  
De xc o m 6  
Acti ve S u bsta nce  
Dasi gl uca g o n  
i ns uli n gl ulisi ne 
N ot a p plica ble 
T y pe  
Dr u g  
Dr u g  
De vice  
D ose F or m ulati o n  
Li q ui d f or m ulati o n, 
0. 6  m L  
Li q ui d f or m ulati o n, d ose 
acc or di n g t o wei g ht (see 
S ecti o n  6. 5. 1 ) 
N ot a p plica ble  
U nit D ose 
Stre n gt h(s)  
0. 6  m g/ 0. 6 m L  
1 0 0 u nits/ m L  
N ot a p plica ble  
D osa ge Le vel(s)  
Si n gle d ose  
C o nti n u o us i nf usi o n  
N ot a p plica ble  
R o ute of 
A d mi nistrati o n  
S u bc uta ne o us i njecti o n  
I V 
N ot a p plica ble  
Use  
E x peri me ntal  
Bac k gr o u n d i nter ve nti o n  
Dia g n ostic  
I M P a n d 
NI M P/ A x M P  
I M P 
NI M P  
N ot a p plica ble  
S o urci n g  
Pr o vi de d ce ntrall y  b y t he 
s p o ns or 
Pr o vi de d b y i n vesti gat or  
Pr o vi de d ce ntrall y  b y t he 
s p o ns or 
Pac ka gi n g a n d 
La beli n g  
S i n gle use pre-fille d 
s yri n ge. Eac h pre-fille d 
s yri n ge will be la bele d as 
re q uire d per c o u ntr y 
re q uire me nt  
A pi dra ®  
De xc o m 6 
( ma n ufact urer: De xc o m) 
will be pr o vi de d b y 
s p o ns or 
A b bre viati o n: C G M =c o nti n u o us gl uc ose m o nit ori n g; I M P =i n vesti gati o nal me dici nal pr o d uct; I V =i ntra ve n o us; 
NI M P = n o n -i n vesti gati o nal me dici nal pr o d uct  
6. 1. 1  Me dic al De vic es  
•  N o s p o ns or ma n ufact ure d sta n d-al o ne me dical de vices ( or de vi ces ma n ufact ure d f or 
s p o ns or b y a t hir d part y) are pr o vi d e d f or us e i n t his trial. 
•  Gl uc ose a nal y zer: Gl u c ose a nal yzer s a v aila ble at t he sites will be use d t o sa m ple plas ma 
gl uc ose.  
•  C G M traci n g : De xc o m G 6 C o nti n u o us Gl uc ose M o nit ori ng S yste m  will be use d t o 
sa m ple gl uc ose le vels a n d will be pr o vi de d b y t he s p o ns or f or use i n t his trial. S p o ns or -
pr o vi de d De x c o m 6 de vices m ust be use d f or all patie nts.  T he C G M de vice will be fitte d 
at t he site after atte n di n g Visit  2  a n d at least 2 h o urs bef ore t he pla n ne d h y p o gl yce mia 
i n d ucti o n. T he De xc o m G 6  C G M will us uall y re q uire a 2 -h o ur war m -u p peri o d t o 
accli matize b ef ore t he se ns or rea di n g will start. T he h y p o gl yce mia i n d ucti o n s h o ul d n ot 
start u ntil t he se ns or war m-u p peri o d is c o m plete d a n d data is recei ve d fr o m se ns or . All 
patie nts m ust re mai n fitte d  wit h t he C G M  u ntil 3 0 0  mi n utes after I M P a d mi nistrati o n . 
Patie nts will be u n der me dical s u per visi o n at all ti mes w hile t he de vice is i n use.  F or t he 
p ur p ose of t his trial, t he de vic e ma y  b e use d o utsi de t he i nte n de d p ur p os e f or patie nts  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 3 1 /7 8  
C O N FI D E N T I A L  
bel o w 2 years  (a p pr o val a p plies t o 2 years a n d ol d er). N o mec ha nical or desi g n c ha n ges 
ha ve bee n ma de t o t he d e vice. T he C G M de vice is use d as i nte n de d acc or di n g t o t he C E 
mar k a n d t he 5 1 0 K  cleara nce,  e xce pt f or usi n g it i n  patie nts bel o w t he a p pr o ve d a ge of 
2  year s.  
•  F or i nterstitial gl uc ose data ge nerate d b y t he De xc o m G 6 C G M S yste m, t he i n vesti gat or 
will e ns ure t hat C G M dat a are d o w nl oa de d fr o m t he de vice at Visit  2.  
•  I nstr u cti o ns f or me dical de vice use are pr o vi de d b y t he ma n ufact urer of t he me dical 
de vice . T he De xc o m G 6 S yste m s h o u l d be use d acc or di n g t o t he ma n ufact urer’s 
i nstr ucti o ns; it d oes n ot re q uire cali brati o n. T he c o ntract res earc h or ga ni zati o n ( C R O) or 
dele gate will ha n dle t he s o urci n g, c o nfi g ur ati o n f or use i n t he trial, pr oce d ures f or d ata 
e xtracti o n, ser vi ce, a n d ret ur n  ha n dli n g f or t he De xc o m G 6 S yste m.  
•  All tec h nical c o m plai nts re gar di n g t he d asi gl uca g o n pre -fille d s yri n ges s h all be 
d oc u me nte d a n d re p orte d b y t he i n vesti gat or t hr o u g h o ut t he trial (see Secti o n  8. 3. 9 ) a n d 
a p pr o priatel y ma n a ge d b y t he s p o ns or.  
6. 2  Pre p ar ati o n/ H a n dli n g/ St or a ge/ A cc o u nt a bilit y  
Dasi gl uca g o n m ust be st ore d i n a refri gerat or ( 3 6° F t o 4 6° F/ 2 ° C t o 8° C). T he i n vesti gat or or 
desi g nee m ust c o nfir m t h at a p pr o priat e c o n diti o ns  i ncl u di n g te m perat ure c o n diti o ns ha ve bee n 
mai ntai ne d d uri n g tra nsit t o a n d st ora ge at site f or all dasi gl uca g o n recei ve d a n d a n y 
discre pa n cies are re p orte d a n d res ol ve d b ef ore use of  dasi gl uca g o n.  
All dasi gl uca g o n m ust be st ore d i n a sec ure, e n vir o n me ntall y 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 nce wit h t he la bele 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 a ut h orize d site staff. 
T he i n vest i gat or or desi g nee  is res p o nsi ble f or dasi gl uca g o n acc o u nta bilit y, rec o nciliati o n, a n d 
rec or d m ai nte na nce (ie, recei pt, rec o nciliati o n, a n d fi nal dis p ositi o n rec or ds). Eac h pre -fille d 
s yri n ge will ha ve a trial u ni q ue dis pe nsi n g u nit n u m ber ( D U N), w hic h is t o be use d f or 
tracea bilit y p ur p oses. 
F urt her g ui d a nce a n d i nf or mati o n relate d t o ha n dli n g a n d pre parati o n  of dasi gl uca g o n i ncl u di n g 
s u p pl y or deri n g, assi g n me nt of dasi gl uca g o n, h a n dli n g of te m perat ure e xc ursi o ns, a n d fi nal 
dis p ositi o n of use d/ u n use d dasi gl uca g o n are pr o vi de d i n t he Trial Materials Ma n ual ( T M M ). 
6. 3  Tri al I nter ve nti o n C o m pli a nce  
Patie nts are d ose d at t he site, t he y will recei ve d asi gl uca g o n  i njecti o n directl y fr o m t he 
i n vesti gat or or desi g nee, u n der me dical s u p er visi o n. T he d ose ( 0. 3 or 0. 6 m g)  a n d date a n d ti me 
of eac h d os e a d mi nistere d will be rec or de d i n t he s o urce d oc u m e nts. T he d ose of dasi gl uca g o n  
a n d trial patie nt i de ntificati o n will be c o nfir me d at t he ti me of d osi n g b y a me m ber of t he trial 
site staff ot her t ha n t he p ers o n a d mi nisteri n g t he trial i nter ve nti o n.  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 3 2 /7 8  
C O N FI D E N T I A L  
6. 4  D ose M o dific ati o n  
N o d ose m o dificati o n is pla n ne d f or t his trial.  
6. 4. 1  Retre at me nt Crit eri a  
N o retreat me nt criteri a are pla n ne d f or t his trial.  
All patie nts e ntere d i nt o t he trial will be treate d at Visit  2. If t he tar get plas ma gl uc ose ca n n ot b e 
ac hie ve d o n t h e d osi n g da y d uri n g t he i n d uce d h y p o gl yce mia pr oce d ure, t h e patie nt ca n b e 
resc he d ul e d as des cri be d i n S ecti o n 5. 5 . 
6. 5  Tre at m e nt a n d D osi n g C o n diti o ns  
Patie nt s will be a d mitte d t o t he cli nic wit h t heir pare nt(s)/le gal g u ar dia n(s) t he ni g ht bef ore or at 
earl y m or ni n g of t he d osi n g da y ( Visit  2 ). T he pati e nt ’s eli gi bilit y will be c hec ke d.  
T he C G M de vice will be fitte d at t he site after atte n di n g Visit  2 a n d at least 2 h o urs bef ore t he 
pla n ne d start of t he h y p o gl yce mia i n d ucti o n. T h e De xc o m G 6 C G M will us uall y re q uire a 2 -h o ur 
war m u p peri o d t o accli matize bef ore t he se ns or rea di n g will start. T he h y p o gl yce mia i n d ucti o n 
s h o ul d n ot start u ntil t he se ns or war m u p p eri o d is c o m plete d a n d dat a is recei ve d fr o m se ns or. 
All patie nts m ust r e mai n fitte d wit h t he C G M de vice u ntil 3 0 0  mi n utes after I M P a d mi nistrati o n.  
F or p atie nts o n m ulti ple d ail y i njecti o n i ns uli n t her a p y  
F or patie nts o n m ulti ple dail y i njecti o ns ( M DI), i ns uli n t hera p y will be a dj uste d at t he discreti o n 
of t he i n vesti gat or i n  t he da ys pri or t o t he d osi n g visit ( Visit 2) wit h t he p ur p ose of ha vi n g as l o w 
as a m bie nt i ns uli n e x p os ure d uri n g t he i nter ve nti o n peri o d o n Da y 1 as p ossi ble. D uri n g t he 
peri o d wit h a dj uste d i ns uli n treat me nt, t he safet y of t he patie nt will be e ns ure d b y  fre q u e nt 
plas ma gl uc ose m o nit ori n g a n d c o ntact wit h t he cli nical site, as nee de d. Details (i ns uli n, d ose 
le vel a n d ti mi n g) re gar di n g t he patie nt’s re g ular i ns uli n t hera p y a n d t he i ns uli n t hera p y i n t he 
da ys pri or t o t he d osi n g visit ( visit 2) will be ca pt ure d i n t he e C R F f or t he i n di vi d ual patie nt.  
F or p atie nts o n i ns uli n p u m p t her a p y  
F or patie nts o n i ns uli n p u m p t hera p y, t he patie nt’s i ns uli n p u m p is st o p pe d a p pr o xi matel y 1  h o ur 
pri or t o d osi n g i n t he m or ni n g of Da y 1, Visit  2.  
Details (i ns uli n, d ose le ve l a n d ti mi n g) re gar di n g t he patie nt’s i ns uli n t hera p y will be ca pt ure d i n 
t he e C R F f or t he i n di vi d ual patie nt. 
6. 5. 1  H y p o gl yce mic C l a m p P r oce d ure a n d D osi n g  
H y p o gl yce mia i n d ucti o n will be i nitiate d usi n g I V i ns uli n t o tar get a plas ma gl uc ose le vel 
bet wee n 7 0 a n d  9 0  m g/ d L ( bet wee n 3. 9 a n d 5  m m ol/ L).  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 3 3 /7 8  
C O N FI D E N T I A L  
I ns uli n ( o nl y i ns uli n gl ulisi ne [ A pi dra® ] will be us e d) will be pr o vi de d b y t he i n vesti gat or. 
I ns uli n i nf usi o n f or I V us e will be pre pare d acc or di n g t o t he patie nt’s b o d y wei g ht at t he d osi n g 
visit.  
Pre parati o n of t he  i ns uli n i nf usi o n: 
•  0. 5  i nter nati o nal u nits i ns uli n gl ulisi ne ( A pi dra® ) per k g b o d y wei g ht 
•  4 8  m L Na Cl 0. 9 %  
Plas ma gl uc ose m ust be c hec k e d usi n g gl uc ose a n al yzer bef ore i nitiati o n of i n d ucti o n of 
h y p o gl yce mia. H y p o gl yce mia will be i n d uce d usi n g i ns uli n I V i nf usi o n rat es acc or di n g t o 
plas ma gl uc ose le vels  acc or di n g t o Ta ble  6 -2 . 
T a ble  6 -2  
I ns uli n I nf usi o n R ates 
Gl uc ose  
I nf usi o n r ate  
I ns uli n d ose (I U/ k g B W/ h)  
> 2 0 0  m g/ d L  
1 0. 0  m L/ h  
0. 1  
1 5 0 – 2 0 0  m g/ d L  
5. 0  m L/ h  
0. 0 5  
9 0 – 1 4 9  m g/ d L  
2. 5  m L/ h  
0. 0 2 5  
< 9 0  m g/ d L  
I ns uli n i nf usi o n st o p!  
0  
A b bre viati o ns: B W = b o d y wei g ht; I U =I nter nati o nal u nits  
T he pr oce d ure t o i n d uce h y p o gl yce mia is gi ve n as a g ui da nce a n d a n y d e viati o n t o i ncrease or 
decrease t he i ns uli n rat e is all o we d at t he discreti o n of t he i n vesti gat or. If t h e tar get plas ma 
gl uc ose ca n n ot be ac hie v e d o n t he d osi n g da y, t he patie nt  ca n be resc h e d ul e d f or a n ot h er visit as 
descri be d i n S ecti o n 5. 5 . 
D uri n g t he i n d ucti o n p hase (d uri n g i ns uli n i nf usi o n) a n d f oll o wi n g t he a d mi nistrati o n of 
dasi gl uca g o n , gl uc ose le vels will be m o nit ore d b y b ot h C G M a n d b y a gl uc ose a nal yzer  (see 
S ecti o n 6. 1. 1 ). Plas ma  gl uc ose le vels s h o ul d prefera bl y be c h ec ke d b y gl u c ose a nal yzer  
a p pr o xi matel y e ver y 1 0  mi n utes w hile gl uc ose  le vels are a b o ve 1 1 0  m g/ d L ( 6. 1  m m ol/ L), a n d 
prefera bl y a p pr o xi matel y e ver y 5  mi n utes o nce gl uc ose  le vels are at or bel o w 1 1 0  m g/ d L 
( 6. 1 m m ol/ L).  Plas ma g l uc ose s h o ul d be c o nfir me d b y t he gl uc ose a n al yzer pri or t o t he 
a d mi nistrati o n of dasi gl uca g o n. After  d osi n g wit h dasi gl uca g o n, o nce gl u c ose le vels reac h 
≥1 1 0  m g/ d L ( 6. 1  m g/ d L), gl uc ose le vels s h o ul d prefera bl y be c h ec k e d a p pr o xi matel y e ver y 
3 0  mi n utes u ntil 3 0 0  mi n utes.  T he m o nit ori n g fre q ue nc y of plas ma gl u c ose via t he gl uc ose 
a nal yzer s h o ul d be a dj ust e d as nee d e d bas e d o n t he c hil d’s b o d y wei g ht t o  e ns ure t hat a 
ma xi m u m of a p pr o xi matel y 1. 5 % is o btai ne d d uri n g t he d osi n g visit  as s pecifie d i n Secti o n  6. 5. 3  
(1. 5 % e q uals 1. 1 3  t o 1. 20  m L/ k g wit h t he t otal bl o o d v ol u me esti mate d t o be 7 5 t o 8 0  m L/ k g) .5  
At t he discreti o n of t he i n vesti gat or, a d diti o nal plas ma gl uc ose meas ure me nts ca n be ta ke n at a n y 
ti me d uri n g t he trial, f or e xa m ple w he n t h ere is a s us pici o n (e g, s y m pt o ms) of a h y p o gl yce mic 
e pis o de. 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 3 4 /7 8  
C O N FI D E N T I A L  
A  cat heter (e g, a n i n d welli n g cat heter) will be i nserte d i nt o t he c hil d’s ar m f or bl o o d dra w f or P K/ P D 
sa m pli n g. If p ossi ble, t he sa me I V access as use d f or i ns uli n i nf usi o n ca n be use d f or t he P K/ P D 
sa m pli n g t o re d uce t he stress a n d disc o mf ort f or t he c hil d. Atte nti o n s h o ul d be ma de t o e ns ure bl o o d 
sa m ples will be c ollecte d fr o m t he circ ulati n g bl o o d v ol u me a n d n ot fr o m a reser v oir dea d s pace 
create d b y t he cat heter. If direct ve ni p u nct ures are c o nsi dere d m ore a p pr o priate , es peciall y f or t h ose 
c hil dre n w here t he n u m ber of P K a n d P D sa m ples are re d uce d (refer t o Ta ble  6 -4 ), ve ni p u nct ures ca n 
be use d i nstea d of i n d welli n g cat heters.  T he cat heter will be place d i n t he m or ni n g pri or t o I M P 
a d mi nistrati o n. Bl o o d sa m ples f or baseli ne assess me nt of plas ma gl uc ose a n d  dasi gl uca g o n P K will 
be c ollecte d a p pr o xi matel y 5  mi n utes after t he gl uc ose c o nce ntrati o n reac hes ≥7 0  m g/ d L a n d 
< 9 0  m g/ d L ( 3. 9 t o 5. 0  m m ol/ L). T hese sa m ples are t he baseli ne sa m ples a n d s h o ul d be c ollecte d 
wit hi n 2  mi n utes bef ore I M P a d mi nistrati o n. T he b aseli ne sa m ples will be se nt t o t he cli nical 
la b orat or y a n d a nal yze d usi n g a se nsiti ve a n d vali date d assa y f or gl uc ose meas ure me nts. T he assa y 
use d f or pri mar y e n d p oi nt gl uc ose meas ure me nts s h o ul d f ulfil t he re q uire me nts of t he U S F D A 
Bi oa nal ytical Met h o d Vali dati o n G ui da nce f or I n d ustr y Secti o n 5 B a n d C f or bi o mar kers. 6 T he 
sa m pli n g pr oce d ure is descri be d i n Secti o n  6. 5. 3 . Bef ore I M P a d mi nistrati o n, it m ust be c o nfir me d 
b y t he gl uc ose a nal yzer t hat t he plas ma gl uc ose is still ≥7 0  m g/ d L a n d < 9 0  m g/ d L.  
If plas ma gl uc ose is < 7 0 m g/ d L ( 3. 9  m m ol/ L), I V gl uc ose s ol uti o n will be a d mi nistere d t o raise 
plas ma gl uc ose t o wit hi n t he 7 0  t o 9 0  m g / d L ( 3. 9 t o 5. 0  m m ol/ L ) tar get ra n ge. T he r u n-i n p eri o d 
will be a de q uatel y e xte n de d (at least 3 0  mi n utes) u ntil t he a b o ve tar get is ac hie ve d, t he gl uc os e 
i nf usi o n has bee n disc o nti n ue d, a n d ne w baseli ne sa m ples f or plas ma gl uc ose will be c ollecte d. 
I n t his case, gl uc ose s h o ul d n ot be i nf use d wit hi n 3 0  mi n utes bef ore I M P a d mi nistrati o n. If 
plas ma gl uc ose is n ot wit hi n t he tar get ra n g e aft er t he sec o n d atte m pt, t he p atie nt  s h o ul d be 
resc he d ul e d f or a ne w treat me nt visit wit hi n 7 da ys ( + 2  da ys).  
Fi g ure  6 -1  
I ns uli n-I n d uce d H y p o gl yce mi a a n d D osi n g 
 
A b bre viati o n s: I V =i ntra ve n o us; P G = p las ma gl uc ose 
N otes: Patie nt s will be a d mitte d t o t he cli nic wit h t heir pare nt(s)/le gal g uar dia n(s) i n t he ni g ht bef ore or at earl y 
m or ni n g of t he d osi n g da y . 
If i ns uli n i nf usi o n is use d; d osi n g s h o ul d n ot be d o ne u ntil at least 5  mi n utes  after i nf usi o n is st o p pe d . 
If gl uc ose i nf usi o n is use d d osi n g s h o ul d n ot be d o ne u ntil at least 3 0  mi n utes  after i nf usi o n is st o p pe d . 
Assess me nts a n d bl o o d sa m pli n g will be perf or me d o n g oi n g fr o m pre -pr oce d ure/ pre -d ose u ntil 3 0 0  mi n utes  p ost -
d ose acc or di n g t o pr ot oc ol.  
 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 3 5 /7 8  
C O N FI D E N T I A L  
Patie nts will n ot be all o we d t o eat or dri n k ( e xce pt water) fr o m 4  h o urs bef ore d osi n g  u ntil 
3 5  mi n ut es after dasi gl uca g o n a d mi nistrati o n . Patie nt s will o nl y  be all o we d t o eat a n d dri n k 
m o deratel y (a p pr o priat e t o t heir b o d y size, wit h a ma xi m u m of 5 0  gr a ms car b o h y drates)  st arti n g 
3 5  mi n utes after I M P a d mi nistrati o n  t o mi ni mize disc o mf ort i n ter ms of p ote ntial na usea. T w o 
h o urs after d osi n g, p atie nts ca n eat a n d dri n k t heir us ual meals. T he a m o u nt a n d t y pe of f o o d a n d 
dri n k c o ns u me d will be rec or de d. Patie nt s s h o ul d re mai n i n be d, t o t he e xte nt p ossi ble, u ntil 
c o m pleti o n of t he test pr oce d ure 3 0 0 mi n utes after d osi n g ( bat hr o o m visits are all o we d).  
6. 5. 2  Resc ue P r o visi o ns f or H y p o gl yce mi a  
D uri n g i ns uli n -i n d uce d h y p o gl yce mia, plas ma gl u c ose le vels as well as t he patie nt  stat us will be 
m o nit ore d cl osel y t hr o u g h o ut t he pr oce d ur e. After a d mi nistrati o n of I M P (t = 0), if t heir gl uc os e 
le vels bec o me t o o l o w, p atie nt s ma y recei ve p ost-treat me nt I V gl uc os e i nf usi o n t o a meli orate 
h y p o gl yce mia, as f oll o ws:  
•  T he I V gl uc os e i nf usi o n s h o ul d be i nitiate d if a patie nt  e x perie nces escalati n g s y m pt o ms 
of h y p o gl yce mia (e g , start of m o derate s y m pt o ms of h y p o gl yce mia) at a n y ti me d uri n g 
t he test pr oce d ure. Gl uc ose i nf usi o n s h o ul d t he n be i nitiate d tar geti n g a plas ma gl uc ose 
le vel > 9 0 m g/ d L . 
•  If plas ma gl uc ose is < 7 0 m g/ d L bet wee n t = 8 a n d t = 3 0  mi n utes , gl uc ose i nf usi o n (e g, 1  t o 
2  m g/ k g a d mi nistere d o ver 5  t o 1 0  sec o n ds) s h o ul d be i nitiate d t o mai ntai n plas ma 
gl uc ose bet wee n 7 0  m g/ d L (i ncl usi ve) a n d 9 0  m g/ d L. Pa use gl uc ose i nf usi o n if plas ma 
gl uc ose is > 9 0  m g/ d L . 
•  If plas ma gl uc ose is < 9 0 m g/ d L at t ≥3 0  mi n utes, gl uc ose i nf usi o n (e g , 2  t o 3  m g/ k g 
a d mi nistere d o ver 5  t o 1 0  sec o n ds) s h o ul d be i nitiate d. Pa use gl uc ose i nf usi o n w he n 
plas ma gl uc ose is > 9 0  m g/ d L . 
6. 5. 3  C ollecti o n of B l o o d S a m ples  
T he t otal bl o o d v ol u me t o be o btai ne d fr o m a n y i n di vi d ual c hil d wit h a b o d y wei g ht of m ore 
t ha n 1 0. 0 k g will be a b o ut 2 2 .5  m L  (see Ta ble  6 -3  a n d Ta ble  6 -4  f or det ails). F or c hil dre n wit h a 
b o d y wei g ht ≤ 1 0. 0 k g, t he fre q u e nc y of P D  (f or efficac y) a n d P K  sa m ples will gra d uall y be 
re d uce d as s pecifie d i n T a ble  6 -4  t o mi ni mi ze t he bl o o d v ol u me o btai ne d  at a si n gle visit (t o 
a p pr o xi mate l y ma xi m u m 1. 5 % of t otal bl o o d v ol u me)  a n d o ver a f o ur-wee k  peri o d  (t o 
a p pr o xi matel y ma xi m u m 3 % of t otal bl o o d v ol u me) . T hese v al ues are wit hi n t he rec o m me n de d 
sc o pe pr o vi de d b y g ui deli nes a n d base d o n a c hil d’s t otal bl o o d v ol u me bei n g 7 5 t o 8 0 m L/ k g .5 
T he f oll o wi n g bl o o d v ol u me will be ta ke n f or eac h sa m ple at eac h visit:  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 3 6 /7 8  
C O N FI D E N T I A L  
T a ble  6 -3  
Bl o o d V ol u mes  
S a m ple t y pe  
Visit 1 ( m L)  
Visit 2 ( m L)  
Visit 3 ( m L)  
 
Bi oc h e mistr y  
2 . 0 0 
- 
2 . 0 0 
 
He m at ol o g y  
1. 2 0  
- 
1. 2 0  
 
A D A  
3 . 0 0 
- 
3 . 0 0 
 
P K *  
- 
5 . 0 0 
- 
 
P D *   
- 
3. 6 0  
- 
 
O nsite -P G  
- 
1 .5 0  
- 
 
S u m f or eac h visit  
6. 2  
1 0 .1  
6. 2  
 
T otal  
 
2 2 . 5 
A b bre viati o ns: A D A = anti -dr u g a nti b o dies; O nsite -P G = o nsit e m o nit ori n g of plas ma gl uc ose; 
P D = p har mac o d y na mics; P K = p har mac o ki netics  
* R efer t o Ta ble  6 -4  f or details o n w hic h PD  a n d P K  sa m ples t o be c ollecte d  base d o n b o d y wei g ht at Visit 1 a n d 
Visit 2 . 
 
T a ble  6 -4  
P D  (f or effic a c y) a n d P K  S a m pli n g  B ase d o n B o d y W ei g ht 
B o d y wei g ht at Visit 2  
Visit 2  
P D s a m ples t o dr a w  
P K s a m ples t o dr a w  
B W > 1 0. 0  k g  
pre -d ose  
1 5 mi n  
3 0 mi n  
pre -d ose  
1 0 mi n  
2 0 mi n  
3 0 mi n  
4 0 mi n  
6 0 mi n  
9 0 mi n  
1 4 0 mi n  
2 2 0 mi n  
3 0 0 mi n  
1 0. 0 ≥ B W > 9. 0  k g  
pre -d ose  
1 5 mi n  
3 0 mi n  
pre -d ose  
1 0 mi n  
2 0 mi n  
3 0 mi n  
4 0 mi n  
6 0 mi n  
9 0 mi n  
1 4 0 mi n  
3 0 0 mi n  
9. 0 ≥ B W > 8. 0  k g  
pre -d ose  
3 0 mi n  
pre -d ose  
1 0 mi n  
2 0 mi n  
3 0 mi n  
4 0 mi n  
6 0 mi n  
9 0 mi n  
1 4 0 mi n  
3 0 0 mi n  
A b bre viati o ns: B W = b o d y wei g ht; P D = p har mac o d y na mics; P K = p har mac o ki netics  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 3 7 /7 8  
C O N FI D E N T I A L  
6. 6  C o nti n ue d Access t o Tri al  I nter ve nti o n A ft er Visit  2  
After t he d osi n g visit ( Visit 2), patie nts s h o ul d ret ur n t o t he sta n dar d of care t hat t he y recei ve d 
pri or t o t he was h -o ut peri o d. T he treati n g p h ysicia n/i n vesti ga t or will be res p o nsi ble f or 
s u per visi n g patie nts’ dia betes ma na ge m e nt after t he d osi n g visit ( Visit 2). T he pare nt(s)/ le gall y 
a ut h orize d re pres e ntati ve ( L A R ) will be e nc o ura g e d t o c o ntact t he i n vesti g at or s h o ul d t he y ha ve 
a n y q uesti o ns a b o ut t he d ail y basal i ns uli n treat me nt after t he ti me of disc h ar ge. If t here are a n y 
safet y c o n cer ns at t he ti me of disc har ge t he i n-h o use visit ca n be e xte n de d at t he discreti o n of t he 
i n vesti gat or. 
6. 7  Tre at m e nt of O ver d ose  
F or t his trial, a n y d ose greater t ha n 0. 6  m g  or 0. 3 m g of  dasi gl uca g o n  f or t he rele va nt b o d y 
wei g ht a n d a ge ra n ges will be c o nsi dere d a n o ver d ose.  
Zeala n d P har m a A/ S rec o m me n ds s y m pt o matic treat me nt i n t he e ve nt of a n o ver d ose.  
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: 
•  C o ntact t he m e dical m o nit or i m me diatel y.  
•  Assess t he patie nt  t o deter mi ne, i n c o ns ultati o n wit h t he m e dical m o nit or, w het her trial 
i nter ve nti o n s h o ul d be i nterr u pte d. 
•  Cl osel y m o nit or t he patie nt  f or a n y A E/ S A E a n d l a b orat or y a b n or malities u ntil 
dasi gl uca g o n  ca n n o l o n g er be det ecte d s yste micall y (at least  1  da y).  
•  D oc u me nt t he q ua ntit y of t he o ver d ose.  
6. 8  C o nc o mit a nt T h er a p y  
Details of a n y c o n c o mita nt me dicati o n m ust be rec or de d i n t he e C R F at tri al e ntr y (ie , at 
scree ni n g). A n y c h a n ges i n c o nc o mita nt me dicati o n m ust be rec or de d i n t he e C R F at eac h visit 
as t he y occ ur .  
Pri or t o t he start of t he cl a m p pr oce d ure, t he patie nt’s eli gi bilit y m ust be c hec ke d. If t he patie nt 
has ta ke n a n y pr o hi bite d me dicati o n, he/s h e will be e xcl u de d fr o m t he d osi n g visit b ut ma y be 
resc he d ul e d 1 t o 7  da ys later. See Secti o n  7  f or p ossi ble reas o ns f or p atie nt disc o nti n uati o n. 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 3 8 /7 8  
C O N FI D E N T I A L  
7  
DI S C O N TI N U A TI O N O F T RI A L  I N T E R V E N TI O N A N D P A TI E N T  
DI S C O N TI N U A TI O N/ WI T H D R A W A L  
7. 1  Disc o nti n u ati o n of Tri al  I nter ve nti o n 
T his is a si n gle d ose i nter ve nti o n.  F or cases w h ere  t he tar get plas ma gl uc os e ca n n ot be achie ve d 
o n t he d osi n g da y  ( Visit 2)  w hile i n d uci n g h y p o gl yce mia, see Secti o n  5. 5 . 
7. 2  P atie nt  Disc o nti n u ati o n/ Wit h dr a w al f r o m t he Tri al  
Partici pati o n i n t he trial is strictl y v ol u ntar y. Patie nt ’s pare nt(s)/le gal g uar dia n(s) will be a d vise d 
t hat t he y are free t o wit h dra w t heir c hil d fr o m partici pati o n i n t his trial at a n y ti me, f or a n y 
reas o n a n d wit h o ut prej u dice. If t he p atie nt ’s pare nt(s)/le gal g uar dia n(s) c h o oses t o ha ve t he 
c hil d wit h dra w n, t he i n vesti gat or m ust be i nf or me d i m me diatel y. T he i n vesti gat or has t he ri g ht 
t o termi nate partici pati o n of a n y patie nt  at a n y ti m e if t he i n vesti gat or dee ms it i n t he patie nt 's 
best i nterest. T he reas o n a n d circ u msta n ces f or wit h dra wal will be d oc u me nte d i n t he e C R F.  
If wit h dra w al occ urs f oll o wi n g a d mi nistrati o n of t he I M P, t he patie nt will be as ke d t o c o nsi der 
c o m pleti n g t he P D sa m pli n g at 3 0  mi n utes a n d partici pate i n t he f oll o w -u p visit at trial Da y  2 9. 
Patie nts s h o ul d be f oll o we d f or A Es f or t he sa m e d urati o n as t h ose w h o are n ot wit h dra w n.  
If trial partici pati o n is ter mi nate d d ue t o a n A E p ossi bl y relate d t o t he I M P or trial e xa mi nati o ns, 
t he patie nt m ust be f oll o we d u p b y a d diti o nal e xa mi nati o ns acc or di n g t o t he me dical j u d g me nt of 
t he i n vesti gat or u ntil t he a b n ormal c o n diti o n is res ol ve d or t he i n vesti gat or dee ms f urt her 
o bser vati o ns or e x a mi nati o ns t o be n o l o n ger me dicall y i n dicate d.  
If a patie nt disc o nti n ues trial partici pati o n d ue t o t he o n g oi n g se vere ac ut e res pirat or y s y n dr o me 
c or o na vir us 2 ( S A R S -C o V -2) gl o b al pa n de mic, i nf or mati o n s h o ul d be ca pt ure d o n t he e C R F s o 
t hat t his ca n be s u m mariz e d i n t he cli nical st u d y re p ort at t he e n d of t he tri al, i n li ne wit h t he 
F D A G ui da n ce o n C o n d uct of Cli nical Trials of Me dical Pr o d ucts d uri n g C O VI D -1 9 P u blic 
Healt h E mer g e nc y ( F D A 2 0 2 0). T he reas o n f or disc o nti n uati o n s h o ul d be rec or de d o n t h e e C R F 
as S A R S -C o V -2/ C O VI D -1 9, if a p plica ble, a n d i ncl u de as ma n y details as p ossi ble. F or e x a m ple, 
s pecific reas o ns ma y i ncl u de, b ut are n ot li mite d t o: 
•  T he patie nt e x hi bits s y m pt o ms c o nsiste nt wit h C O VI D -1 9.  
•  T he patie nt has a p ositi ve test res ult f or S A R S -C o V -2.  
•  T he patie nt has neit her s y m pt o ms n or a p ositi ve test b ut has c h ose n t o disc o nti n ue st u d y 
partici pati o n d ue t o C O VI D -1 9 c o n cer ns.  
7. 3  L ost t o F oll o w -U p  
A patie nt  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 tri al site. 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 3 9 /7 8  
C O N FI D E N T I A L  
T he f oll o wi n g acti o ns m ust be ta ke n if a p atie nt  fails t o ret ur n t o t he cli nic f or a re q uire d trial 
visit:  
•  T he site m ust atte m pt t o c o ntact t he patie nt’s p are nt(s)/ le gal g uar dia n(s) a n d resc he d ul e 
t he misse d visit as s o o n as p ossi ble a n d ascertai n w het her or n ot t he p atie nt  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 p atie nt  is dee me d l ost t o f oll o w-u p, t he i n vesti gat or or desi g ne e m ust ma ke 
e ver y eff ort t o r e gai n c o ntact wit h t he patie nt’s pare nt(s)/ le gal g uar dia n(s) ( w here 
p ossi ble, tele p h o ne calls a n d, if necessar y, a certifie d letter t o t he last k n o w n maili n g 
a d dress  of t he p atie nt’s p are nt(s)/ le gal g uar dia n(s) or l ocal e q ui vale nt met h o ds). T hese 
c o ntact atte m pts s h o ul d be d oc u me nte d i n t he p atie nt ’s me dical r ec or d. 
•  S h o ul d t he patie nt’s pare nt(s)/ le gal g uar dia n(s) c o nti n ue t o be u nreac ha bl e, t he patie nt 
will be c o nsi dere d t o ha v e wit h dra w n fr o m t he trial. 
Disc o nti n uati o n of s pecific sites or of t he trial as a w h ole are h a n dle d as p art of  A p pe n di x 1 . 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 4 0 /7 8  
C O N FI D E N T I A L  
8  
T RI A L  A S S E S S M E N T S A N D P R O C E D U R E S  
T he f oll o wi n g assess me nts a n d meas ure me nts will be carrie d o ut at t he ti mes s pecifie d i n t he 
trial sc he d ule of assess me nts (S o A ) (Ta bl e  1 -1 ). 
I nf or me d c o ns e nt will be o btai ne d pri or t o a n y trial-relate d pr oce d ures; see Secti o n 1 0. 1. 3 . 
•  Trial  pr oce d ures a n d t h eir ti mi n g are s u m marize d i n t he S o A. Pr ot oc ol wai vers or 
e xe m pti o ns are n ot all o w e d.  
•  I m me diat e safet y c o ncer ns s h o ul d be disc usse d wit h t he s p o ns or i m me diatel y u p o n 
oc c urre nce or a w are ness t o deter mi ne if t he patie nt  s h o ul d c o nti n ue or disc o nti n ue trial 
i nter ve nti o n. 
•  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 S o A, is 
esse ntial a n d re q uire d f or trial c o n d uct.  
•  All scree ni n g ass ess me nts m u st be c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial 
patie nt s meet all eli gi bilit y criteria. T h e i n vesti gat or will mai ntai n a scree ni n g l o g t o 
rec or d details of all patie nt s scree ne d a n d t o c o nfir m eli gi bilit y or rec or d reas o ns f or 
scree ni n g f ail ure, as a p plica ble.  
•  Pr oce d ures c o n d ucte d as part of t he patie nt ’s r o uti ne cli nical ma na g e me nt (e g, bl o o d 
c o u nt) a n d o btai ne d b ef ore si g ni n g of t he I C F ma y be utilize d f or scree ni n g or baseli ne 
p ur p oses pr o vi de d t he pr oce d ures m et t he pr ot oc ol -s pecifie d criteria a nd were perf or m e d 
wit hi n t he ti me fra me defi ne d i n t he S o A.  
8. 1  Assess m e nts  a n d S c he d ule of M e as ure m e nts  
8. 1. 1  Scree ni n g V isit 
Patie nt s will c o me t o t he trial site f or scree ni n g ass ess me nts . Pri or t o a n y trial-relat e d pr oce d ures, 
t he i nf or me d c o nse nt pr oce d ure will be perf or me d; t he trial will be e x plai ne d i n detail t o t he 
patie nt s’ pare nt(s)/le gal g uar dia n(s) a n d c o ns e q ue ntl y t he I C F will be si g ne d b y le gall y 
res p o nsi ble i n di vi d ual(s) per local r e g ulati o ns. T he n, t he scree ni n g pr oce d ures will be perf or me d 
as descri be d i n t he S o A . 
C o nse nte d  patie nts will be pr o vi de d wit h a Patie nt I d e ntificati o n Car d (I D car d), stati n g t hat t he 
patie nt is partici pati n g i n t he trial a n d w h o m t o  c o ntact (site a d dress, I n vesti gat or na me a n d 
tele p h o ne n u m ber). T he patie nts’ pare nt(s)/le gal g uar dia n(s)  s h o ul d b e i nstr ucte d t o ret ur n t he I D 
car d t o t he I n v esti gat or at t he last visit or t o destr o y t he car d after t h e last visit.  
At scree ni n g ( Visit  1), t he f oll o wi n g assess me nts will ta ke place: 
•  I nf or me d c o ns e nt 
•  I n cl usi o n/e xcl usi o n criteria 
•  De m o gra p h y  
•  B o d y meas ure me nts  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 4 1 /7 8  
C O N FI D E N T I A L  
•  Dia betes dia g n osis a n d c urre nt dia bet es treat me nt  
•  Me dical hist or y i ncl u di n g c o nc o mita nt ill nesses  
•  Pri or a n d c o nc o mita nt m e dicati o ns  (i ncl u di n g i nf or mati o n o n pri or use of 
Z E G A L O G U E ®  a n d ot h er gl uca g o n pr o d ucts  [ n u m ber of ti mes use d, date of last ti me 
use d] )  
•  P h ysical e xa mi nati o n  
•  Vital si g ns  
•  1 2 -lea d E C G 
•  A Es  
•  Bi oc he mistr y a n d he mat ol o g y  
•  A nti b o dies a gai nst dasi gl uca g o n   
8. 1. 2  D osi n g V isit 
T h e d osi n g v isit ( Visit 2)  will ta ke place 4  t o 7  wee ks after Visit  1 i n or der t o all o w s ufficie nt 
rec o ver y bet w ee n bl o o d dra ws i n or der t o acc o m m o date pe diatric v ol u me restricti o ns. Patie nt s 
will be a d mitte d t o t he cli nic wit h t heir pare nt(s) /l e gal g uar dia n(s) i n t he ni g ht bef ore or at earl y 
m or ni n g of t he d osi n g da y ( Da y  1). T h e patie nt ’s eli gi bilit y will be c hec ke d. 
T he f oll o wi n g assess me nts will ta ke place:  
•  I n cl usi o n/e xcl usi o n criteria ( pri or t o t he start of t h e i ns uli n-i n d uce d h y p o gl yce mic 
pr oce d ure. C hec k of e xcl usi o n criteria at cli nic a d missi o n o n Visit 2 a n d c ha n ges bet wee n 
scree ni n g visit [ Visit 1] a n d Visit  2)  
•  B o d y meas ure me nts  
•  Dia betes dia g n osis a n d c urre nt dia bet es treat me nt  
•  C o nc o mita nt me dicati o ns ( pri or t o t he start of t he i ns uli n -i n d uce d h y p o gl ycemic 
pr oce d ure , a n d d uri n g a n d after t he i ns uli n -i n d uce d h y p o gl yce mic pr oce d ure) 
•  E xcl usi o n criteria at cli nic a d missi o n ( pri or t o t he start of t he i ns uli n -i n d uce d 
h y p o gl yce mic pr oce d ure)  
•  I ns uli n-i n d uc e d h y p o gl yce mia 
•  P h ysical e xa mi nati o n  
•  Vital si g ns ( pri or t o t he start of t he i ns uli n -i n d uce d h y p o gl yce mic pr oce d ure [ wit hi n 3 0 
mi n utes], a n d at 3 0, 6 0 a n d 3 0 0 mi n utes after d osi n g. T he act ual ti me of t h e assess me nt 
s h o ul d n ot de viate fr o m t he n o mi nal ti me b y m ore t ha n ± 1 0 mi n utes)  
•  L ocal t olera bilit y (at 3 0, 1 2 0,  a n d 3 0 0 mi n utes aft er d osi n g. T he act ual ti me of t he 
assess me nt s h o ul d n ot de viate fr o m t he n o mi nal ti me b y m ore t ha n ±  1 0  mi n utes)  
•  A Es  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 4 2 /7 8  
C O N FI D E N T I A L  
•  Plas ma dasi gl uca g o n , P K sa m pli n g  as per Ta ble  6 -4 . T he act ual ti me of bl o o d sa m pli n g 
s h o ul d n ot de viate fr o m t he n o mi nal ti me b y m ore t ha n ± 1  mi n ute. Pre -d ose is defi ne d as 
wit hi n 2  mi n utes pri or t o d osi n g.  
•  Plas ma gl uc ose  (P D ) sa m pli n g as per Ta ble  6 -4 . T he act ual ti me of bl o o d sa m pli n g 
s h o ul d n ot de viate fr o m t he n o mi nal ti me b y m ore t ha n ± 1  mi n ute f or t he c ollecti o n ti me 
p oi nts. Pre -d ose  is defi ne d as wit hi n 2 mi n utes pri or t o d osi n g ).  
•  If res c ue treat me nt is re q uire d bef ore 3 0 mi n utes after d osi n g, a bl o o d sa m ple f or plas ma 
gl uc ose ( P D sa m ple) will be c ollecte d j ust bef ore start of res c ue treat me nt. N o f urt her 
plas ma gl uc ose ( P D sa m ple) sa m ples are re q uire d after resc u e treat me nt h as bee n 
e m pl o ye d . 
•  Plas ma gl uc ose usi n g gl uc ose a nal y zer d uri n g i n d ucti o n of h y p o gl yce mia a n d u ntil 
3 0 0  mi n utes after d osi n g.  Plas ma gl uc ose le vels m ust be c hec k e d b y gl uc os e a nal yzer 
a p pr o xi matel y e ver y 1 0  mi n utes w hile gl uc ose le vels are a b o ve 1 1 0  m g/ d L ( 6. 1  m m ol/ L), 
a n d a p pr o xi matel y e v er y 5  mi n utes o nce gl uc ose l e vels are at or bel o w 1 1 0  m g/ d L 
( 6. 1 m m ol/ L). Plas ma gl uc ose s h o ul d be c o nfir me d b y t he gl uc ose a n al yzer pri or t o t he 
pre -d ose P K a n d P D sa m pl es a n d pri or t o t he a d mi nistrati o n of dasi gl uca g o n. After 
d osi n g wit h dasi gl uca g o n, o nce gl uc ose le vels reac h ≥1 1 0  m g/ d L ( 6. 1  m g/ d L), gl uc ose 
le vels s h o ul d be c hec ke d a p pr o xi matel y e ver y 3 0 mi n utes u ntil 3 0 0  mi n utes.  
•  Gl uc ose le vels usi n g C G M d uri n g i n d ucti o n of h y p o gl yce mia a n d u ntil 3 0 0  mi n utes after 
d osi n g.  De xc o m 6 will be fitte d i n t he m or ni n g at V isit 2  a n d m ust re mai n fitte d u ntil 
3 0 0  mi n utes after I M P a d mi nistrati o n.  
•  A d mi nistrati o n of I M P ( d uri n g h y p o gl yce mic cla m p pr oce d ure) 
8. 1. 3  F oll o w -u p V isit 
A f oll o w -u p visit ( Visit 3) is pla n ne d 4 wee ks after t he d osi n g da y visit t o assess:  
•  C o nc o mita nt me dicati o ns  
•  Dia betes dia g n osis a n d c urre nt dia bet es treat me nt  
•  P h ysical e xa mi nati o n  
•  Vital si g ns  
•  L ocal t olera bilit y  
•  A Es  
•  Bi oc he mistr y a n d he mat ol o g y  
•  A nti b o dies a gai nst dasi gl uca g o n   
•  E n d -of -trial stat us 
Patie nt s wit h a nti-dasi gl uca g o n a nti b o dies (tr eat m e nt -i n d uce d or treat me nt-b o oste d [titer 
i ncreas e a b o ve 4-f ol d]) at Visit  3  will be i n vite d f or f oll o w -u p A D A s a m pli n g  a p pr o xi matel y  
6  m o nt hs after t heir f oll o w -u p visit  (refer t o Ta ble  1 -1  visit x) . If n o cli nicall y rele va nt o utc o mes 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 4 3 /7 8  
C O N FI D E N T I A L  
relate d t o a nti-dasi gl uca g o n a nti b o dies are d etecte d d uri n g t his 6 -m o nt h f oll o w -u p peri o d or t he 
A D A has r et ur ne d t o bas eli ne, f urt her f oll o w -u p s a m pli n g s h o ul d be disc o nti n ue d. If cli nicall y 
rele va nt o utc o mes h a ve b ee n dete cte d a n d t he p atie nt  is still A D A-p ositi ve, a f urt her s a m ple will 
be c ollecte d after a n ot her 6  m o nt hs.  
8. 2  S afet y Ass ess m e nts  
8. 2. 1  P h ysic al E x a mi n ati o ns  
P h ysical e xa mi nati o n is perf or me d at scree ni n g ( Visit  1), d osi n g ( Visit  2 , pri or t o d osi n g) a n d 
e n d-of -tri al ( Visit 3).  
P h ysical e xa mi nati o n i ncl u des e xa mi nati o n of t he f oll o wi n g b o d y s yste ms: hea d, ears, e y es, 
n ose, t hr oat (i ncl u di n g t he t h yr oi d gla n d), heart, l u n g, c hest , a b d o me n, s ki n, m usc ul os keletal 
s yste m, ner v o us s yste m , a n d l y m p h n o des. 
8. 2. 2  Vit al Si g ns  
Vital si g ns will be meas ure d at scree ni n g ( Visit  1), d osi n g ( Visit  2) a n d e n d -of -trial ( Visit 3 ). 
Bl o o d press ure, p ulse a n d b o d y te m perat ur e will be meas ure d after 5 mi n utes i n a seate d 
p ositi o n . See t he S o A ( Secti o n  1. 3 ) f or t he ti mi n g of vital si g n meas ure me nts at t he d osi n g visit . 
8. 2. 3  Electr oc a r di o gr a ms  
A 1 2 -lea d E C G assess me nt will be perf or me d at scree ni n g ( Visit 1). Details fr o m t he E C G 
assess me nts will be r ec or de d, i ncl u di n g heart rate, P R , Q R S, a n d Q T  i nter val a n d Q Tc c orrecte d 
b y Fri deri cia´s f or m ula i nter val  ( Q T c F). I n case t he Q Tc F val ues are n ot r ea dil y a vaila ble fr o m 
t he E C G mac hi ne, sites m ust perf or m t he calc ulati o n base d o n t he rele va nt para meters obtai ne d 
fr o m t he de vic e. 
8. 2. 4  L oc al T oler a bilit y  
L ocal t olera bilit y assess me nts at 3 0, 1 2 0, a n d 3 0 0  mi n utes  after I M P a d mi nistrati o n  will be 
perf or me d t o assess t he f oll o wi n g:  
•  S p o nta ne o us pai n  
•  Pai n o n pal pati o n  
•  Itc hi n g 
•  Re d ness  
•  E de ma  
•  I n d urati o n/i nfiltrati o n 
•  Ot her  
I nje cti o n site reacti o ns a n d a n y fi n di n gs will be re p orte d as A Es (see Secti o n 8. 3 ). 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 4 4 /7 8  
C O N FI D E N T I A L  
8. 2. 5  Cli nic al S afet y L a b or at or y Assess m e nts  
See A p pe n di x 2  f or t h e list of cli nical la b orat or y t ests t o be perf or me d a n d t o t he S o A 
(Secti o n  1. 3 ) f or t he ti mi n g a n d fre q u e nc y. 
8. 3  A E s, SA Es , a n d Ot he r S afet y Re p orti n g 
T he defi niti o ns 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 . 
A Es will be re p orte d b y t he patie nt  ( or, w he n a p pr o priate, b y a care gi ver, p are nt , or t he p atie nt 's 
L A R ). 
T he i n vesti gat or a n d a n y q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d 
rec or di n g e ve nts t hat meet t he defi niti o n of a n A E or S A E a n d re m ai n res p o nsi ble f or f oll o win g 
u p all A Es .  
T he met h o d of rec or di n g, e val uati n g, a n d ass essi n g ca usalit y of A Es a n d S A Es a n d t he 
pr oce d ures f or c o m pleti n g a n d tra 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 . 
8. 3. 1  Ti m e 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 will be c ollecte d fr o m t he first trial-relate d acti vit y after si g ni n g of t he I C F 
u ntil t he e n d of t he p ost-treat me nt f oll o w-u p p eri o d ( w hic h ma y i ncl u de c o ntacts f or f oll o w -u p of 
safet y) at t he ti me p oi nts  s pecifie d i n t he S o A (Secti o n  1. 3 ). 
All S A Es will be rec or de d a n d re p ort e d t o t he s p o ns or or desi g nee i m me di atel y a n d u n der n o 
circ u msta nce s h o ul d t his e xcee d 2 4  h o urs, as i n dicate d i n A p pe n di x 3 . T he i n vesti gat or will 
pr o vi de  a n y u p date d S A E data t o t he s p o ns or wit hi n 2 4  h o urs of it bei n g a vaila ble.  
I n v esti gat ors are n ot o bli gate d t o acti vel y see k i nf or mati o n o n A Es or S A Es after c o n cl usi o n of 
t he trial partici pati o n . H o we ver, if t h e i n vesti gat or lear ns of a n y S A E, i n cl u di n g a deat h, at a n y 
ti me after a p atie nt  has b ee n disc har ge d fr o m t he trial, a n d he/s he c o nsi ders t he e ve nt t o be 
reas o na bl y relate d t o t he trial i nter ve nti o n or trial partici pati o n, t he i n vesti gat or m ust pr o m ptl y 
n otif y t he s p o ns or. 
8. 3. 2  Met h o d of Detecti n g A Es a n d S A Es  
Care will 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 b al q uesti o ni n g of t he patie nt  a n d patie nt ’s pare nt(s)/le gal g uar dia n(s) is t he 
preferre d m et h o d t o i n q uire a b o ut A E  occ urre nces.  I n a d diti o n, patie nts will be o bser ve d f or a n y 
si g ns or s y m pt o ms. 
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 ort, 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 patie nt  at 
s u bse q ue nt visits/c o ntacts. All S A Es, a n d A Es of s pecial i nterest ( as defi n e d i n A p pe n di x 3 ), will 
be f oll o we d u ntil res ol uti o n, sta bilizati o n,  t he e ve nt is ot her wise e x plai ne d, or t he patie nt  is l ost 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 4 5 /7 8  
C O N FI D E N T I A L  
t o f oll o w-u p (as defi ne 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 pr oce d ures is pr o vi de d 
i n A p pe n di x 3 . 
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 t he s p o ns or 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 patie nt s a n d t he safet y of a trial 
i nter ve nti o n u n der cli nic al i n vesti gati o n are met. 
T he s p o ns or has  a l e gal r es 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 g e ncies a b o ut t he safet y of a trial i nter ve nti o n u n der cli nical i n vesti gati o n. T he 
s p o ns or will c o m pl y wit h c o u ntr y-s pecific re g ul at or y re q uire m e 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 ority, I nstit uti o nal Re vie w B oar ds (I R B)/I n de pe n d e nt Et hics C o m mittees 
(I E C), a n d i n vesti gat ors. 
A n i n vesti gat or w h o recei ves a n i n vesti gat or safet 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 t he s p o ns or will re vie w a n d t h e n file it 
al o n g wit h t he IB  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.  
I n v esti gat or safet y re p orts m ust be pre pare d f or s us pecte d u ne x p ecte d s eri o us a d verse reacti o ns 
acc or di n g t o l ocal re g ulat or y re q uire m e nts a n d s p o ns or p olic y a n d f or war de d t o i n vesti gat ors as 
necessar y.  
8. 3. 5  A E s of S peci al I nterest 
A n A E  of s pecial i nterest ( A E SI ) is a n e v e nt t hat, i n t he e val uati o n of safet y, has a s peci al f oc us 
(e g, re q uir e d b y healt h a ut h orities). I n t his trial, h e m o d y na mic c ha n g es are c o nsi dere d A E SIs 
t hat are defi ne d as f oll o ws: 
•  P ost -d ose cli nical si g ns, or meas ure d vital si g ns, i n dicati n g a c li nicall y si g nifica nt dr o p i n 
bl o o d press ure i ncl u di n g si g ns of ort h ostatic h y p ote nsi o n, vas o va gal res p o nses, or 
bra d ycar dia.  
•  P ost -d ose c ha n ge i n p uls e or bl o o d press ur e c o nsi dere d a n e ve nt of h y p o - or h y perte nsi o n 
as j u d ge d b y t he i n vesti gat or. 
A E SIs m ust be re p orte d t o t he s p o ns or i n t he sa me wa y a n d wit h t he sa me ti meli nes as S A Es 
(see Secti o n  8. 3. 1  a n d A p pe n di x 3 ). 
8. 3. 6  H y p o gl yce mi a  
H y p o gl yce mia will be re gar de d as a n A E, rec or de d, a n d d oc u me nte d o n a n A E f or m ( or S A E 
f or m, if a p plica ble). 
Si nce h y p o gl yce mia will be i n d uce d d uri n g t he d osi n g visit, i n acc or da nce wit h h y p o gl yce mia 
cla m p pr oce d ure d escri b e d i n Secti o n  6. 5. 1 , O N L Y plas ma gl uc ose bel o w 3. 0 m m ol/ L 
( 5 4 m g/ d L) m ust be re p orte d as a n A E, at t he d osi n g visit ( Visit  2), or  at i nsta nces t hat I V 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 4 6 /7 8  
C O N FI D E N T I A L  
gl uc ose is gi ve n after I M P a d mi nistrati o n.  T he h y p o gl yce mic e ve nt s h o ul d be c o nfir me d b y 
gl uc ose a nal yz er. If o nl y t he C G M de vice is use d, t he h y p o gl yce mic e v e nt s h o ul d be prese nt f or 
at least 1 5  mi n utes bel o w 3. 0  m m ol/ L f or A E re p orti n g.  
8. 3. 7  H y perse nsiti vit y  
If a p ote ntial h y perse nsiti vit y reacti o n is o bser ve d, a d diti onal bl o o d sa m ples, as cli nicall y 
i n dicate d, ma y be re q uire d t o f urt her c h aracterize t he p ote ntial h y perse nsiti vit y reacti o n. If a n 
a na p h ylactic s h o c k is s us pecte d, sa m ples ma y b e t a ke n f or t h e meas ure me nt of tr y ptase. I n t his 
case, a bl o o d s a m ple s h o ul d be  ta ke n 3 t o 4 h o urs after t he e ve nt a n d a gai n a p pr o xi matel y 1 t o 
2  wee ks later t o deter mi n e tr y ptase bas eli ne le vels. I n a d diti o n, assess me nts f or ele vate d 
hista mi ne le vels ma y be c o nsi dere d.  
8. 3. 8  Ot her I m p ort a nt E ve nts  
T he f oll o wi n g e ve nts m ust al wa ys be re p orte d t o t he s p o ns or acc or di n g t o S A E ti meli nes, 
re gar dl ess of w het h er t he e ve nt is n o n-seri o us or s eri o us: 
•  Ris k of li ver i nj ur y defi ne d as A L T  or A S T  > 3  ×  U L N a n d t otal bilir u bi n > 2  ×  U L N, 
w here n o alter nati ve eti ol o g y e xists  
•  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  
•  O ver d ose of t he I M P  
•  S us pecte d a b use or mis use of t he I M P  
•  Me dicati o n err or i n v ol vi n g t he I M P  
•  I n a d vert e nt or acci de ntal e x p os ure t o t he I M P 
8. 3. 9  H a n dli n g of Tec h nic al C o m pl ai nts Re g ar di n g D asi gl uc a g o n Pre -fille d S yri n ges 
A tec h n ical c o m plai nt is a n y c o m m u nicati o n t hat alle ges pr o d uct (I M P) deficie ncies relate d t o 
t he i de ntit y, q ualit y, d ura bilit y, relia bilit y, safet y, effecti ve ness, or p erf or ma nce. T h e tec h nical 
c o m plai nt ma y or ma y n ot be ass ociate d wit h a n A E.  
Rec or di n g a n d F ol l o w-u p of Tec h nic al C o m pl ai nts  
Tec h nical c o m plai nts m ust be rec or de d o n a tec h nical c o m plai nt f or m i n t he e C R F. If t h e e C R F 
is n ot a vaila ble, a pa p er f or m m ust be fille d o ut, a n d t he e C R F m ust be fille d o ut w he n a v aila ble. 
Ti m eli nes f or Re p orti n g of Tec h ni c al C o m pl ai nts  
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 e C R F wit hi n:  
•  2 4  h o urs if relate d t o a S A E  
•  5  cale n dar da ys f or all ot her tec h nical c o m plai nts  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 4 7 /7 8  
C O N FI D E N T I A L  
A n y A E/ S A E ass ociate d wit h a tec h nical c o m plai nt m ust be re p orte d i n acc or da nce wit h 
A p pe n di x 3 . T he relati o ns hi p bet wee n t he tec h nical c o m plai nt a n d t he A E/ S A E m ust be assesse d 
b y t he i n vesti gat or.  
F oll o w -u p o n 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 a n d/ or u p d ate d i nf or mati o n is rec or de d o n 
t he ori gi nal tec h nical c o m plai nt f or m. 
C ollecti o n a n d shi p me nt of tec h nic al c o m pl ai nt s a m ple (s) (I M P) 
T he i n vesti gat or m ust c ollect t he tec h nic al c o m plai nt sa m ple (s) a n d all ass o ciate d parts 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. T he m o nit or m ust c o or di nate 
t he s hi p me nt of t he sa m ple a n d ass ociat e d parts as per i nstr ucti o n fr o m t he s p o ns or. 
8. 4  P h ar m ac o ki netics  
T he e x p os ure t o d asi gl uca g o n f or ass ess me nt of P K will be assesse d bas e d o n plas ma 
c o nce ntr ati o n data fr o m s a m ples c ollecte d at t he d osi n g visit ( Visit 2):  
•  A rea u n d er t he plas ma c o nce ntrati o n vers us ti me c ur ve ( A U C) fr o m 0 t o 3 0 mi n utes p o st-
d ose  ( A U C0 -3 0 mi n) 
•  A U C  fr o m 0 t o 3 0 0 mi n utes p ost -d ose  ( A U C0 -3 0 0 mi n) 
•  A U C fr o m 0 t o t he last ti me p oi nt wit h a meas ure d c o nce ntr ati o n ( A U C 0 -t) 
•  A U C fr o m 0 t o i nfi nit y p ost -d ose ( A U C0 -i nf) 
•  M a xi m u m o bser ve d c o nce ntrati o n  (C ma x ) 
•  T i me t o Cma x  (T ma x ) 
•  Ter mi nal eli mi nati o n rate c o nsta nt of plas ma dasi gl uca g o n ( λz)  
•  Ter mi nal plas ma eli mi nati o n half -life of dasi gl uca g o n (t½ ) 
•  T otal b o d y cleara nce of plas ma dasi gl uca g o n ( C l/f) 
•  V ol u me of distri b uti o n of plas ma dasi gl uca g o n ( Vz/f)  
•  Mea n resi de n ce ti me of plas ma dasi gl uca g o n ( M R T)  
Bl o o d sa m ples of a p pr o xi matel y 5  m L will be c ollecte d f or meas ure me nt of plas ma 
c o nce ntr ati o ns of dasi gl uca g o n  (refer t o Ta ble  6 -4 ). T he sa m pli n g pr oce d ure is descri be d i n 
Secti o n  6. 5. 3 . 
8. 5  P h ar m ac o d y n a mics  
T he plas ma gl uc ose pr ofile f or assess me nt of t he pri mar y a n d sec o n dar y cli nical effi cac y 
e n d p oi nts will be assesse d base d o n plas ma gl uc os e c o nce ntrati o n data fr o m sa m ples c ollecte d at 
t he d osi n g visit ( Visit 2).  Bl o o d sa m ples of a p pr o xi matel y 3 . 6 m L will be c ollecte d f or 
meas ure me nt of t h e plas ma  gl uc ose res p o ns e  (refer t o Ta ble  6 -4 ). T he s a m ples will be se nt t o t he 
cli nical la b orat or y a n d a n al yze d usi n g a se nsiti ve a n d vali date d assa y f or gl uc o se meas ure me nts. 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 4 8 /7 8  
C O N FI D E N T I A L  
T he assa y use d f or pri mar y e n d p oi nt gl uc ose meas ure me nts s h o ul d f ulfil t he re q uir e me nts of t he 
U S F D A Bi oa nal ytical Met h o d Vali dati o n G ui da nce f or I n d ustr y Secti o n 5 B a n d C f or 
bi o mar kers. 6 T he sa m pli n g pr oce d ure is descri be d i n Secti o n  6. 5. 3 . 
Plas ma g l uc ose will be meas ure d b y gl u c ose a n al yzer d uri n g i n d ucti o n of h y p o gl yce mia  at site. 
Plas ma gl uc ose s h o ul d be c o nfir me d b y t h e gl uc ose a nal yzer pri or t o t he pre-d ose P K a n d P D 
sa m ples a n d pri or t o t he a d mi nistrati o n of dasi gl uca g o n (at V isit 2).  Plas m a gl uc ose le vels at 
baseli ne  m ust be e ntere d i nt o t he e C R F.  
F urt her m ore, gl uc ose l e v els wi ll be meas ure d b y C G M. I n v esti gat or m ust e ns ure t hat C G M data 
are c ollecte d. 
8. 6  I m m u n o ge nicit y Assess m e nts 
Assess me nt of a nti b o dies a gai nst dasi gl uca g o n is descri be d i n  A p pe n di x 2 . 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 4 9 /7 8  
C O N FI D E N T I A L  
9  
S T A TI S TI C A L C O N SI D E R A TI O N S  
9. 1  St atistic al H y p ot heses  
N o h y p ot heses are pre -s p ecifie d, a n d n o i nfere ntial testi n g will be carrie d o ut. 
9. 2  S a m ple Size Deter mi n ati o n  
Ei g ht c hil dre n will be treate d i n t his trial. T he n u m ber of c hil dre n is n ot b ase d o n a f or mal 
sa m ple size calc ulati o n, e val uati n g t he p o wer of t he trial, h o we ver s o me c o nsi derati o ns ha ve 
bee n ma de wit h res pect t o t he precisi o n of t he esti mate of t he pri mar y e n d p oi nt . I n a pre vi o us 
pe diatric trial wit h dasi gl uca g o n, t he mea n plas ma gl uc ose c ha n g e fr o m bas eli ne at 3 0  mi n utes 
after I M P i njecti o n w as 9 6 m g/ d L wit h a sta n dar d de viati o n ( S D) of 2 0  m g/ d L i n c hil dre n a ge d 
6  t o 1 1  years. Ass u mi n g t he variati o n is t he sa me i n c hil dre n <  6  years  of a g e , a 9 5 % c o nfi de nce 
i nter val will ha ve a wi dt h of ±  2 5  m g/ d L ar o u n d t he mea n plas ma gl uc os e c ha n ge, w he n 
8  c hil dre n are treate d.  
9. 3  A n al ysis Sets  
F or t he p ur p os es of a n al ysis, t he f oll o wi n g a nal ysis sets are defi ne d:  
•  Safet y a nal ysis set ( S A F): All patie nts w h o  were e nr olle d a n d recei ve d at least 1  d ose of 
I M P 
•  F ull a nal ysis set ( F A S): All patie nts of t he S A F  
9. 4  St atistic al A n al yses  
T he statistical a nal ysis pla n will be fi nalize d pri or t o data base l oc k, a n d it will i ncl u de tec h nical 
a n d detaile d des cri pti o n of t he statistical a nal yses descri be 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 he 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 ke y sec o n dar y e n d p oi nts.  
9. 4. 1  Ge ne r al C o nsi der ati o ns  
All data c ollecte d i n t his trial a n d d oc u me nte d i n t he e C R Fs will be pres e nte d i n data listi n gs. All 
e n d p oi nts will be s u m marize d usi n g descri pti ve statistics. C o nti n u o us data will be s u m marize d i n 
ta bles usi n g n u m ber of p atie nt s ( n), mea n, me di a n, S D, mi ni m u m a n d ma xi m u m b y trial ti me 
p oi nt. I n a d diti o n, 9 5 % c o nfi de nce i nter vals ( bas e d o n a t distri b uti o n if n ot ot her wise state d) 
will be calc ulate d if a p pr o priate a n d det aile d i n t he ta ble s hells. F or l o g arit h m-tra nsf or me d data 
(rele v a nt f or sele cte d P K s u m maries), t he ge o metri c mea n a n d c oefficie nt of variati o n % will 
als o be pr o vi de d. Cate g orical data will be s u m marize d usi n g t he c o u nt a n d perce nt a ge.  
I n case of ter mi nati o n of t he trial, all data c ollect e d u p t o t hat ti me p oi nt will be incl u de d i nt o t he 
a nal ysis.  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 5 0 /7 8  
C O N FI D E N T I A L  
All ta bles, fi g ures a n d d ata listi n gs  will be ge nerate d usi n g S A S ©  s oft ware Versi o n 9 or hi g her 
( S A S I nstit ute, I nc, Car y, N ort h Car oli na, U S A). 
9. 4. 2  Pri m ar y E n d p oi nt  
T he pri mar y effic ac y e n d p oi nt, p las ma gl uc ose c o nce ntrati o n c h a n ge fr o m baseli ne at 3 0  mi n utes 
after trial pr o d uct i njecti o n or at t he ti me of res c u e b y I V gl uc ose  if bef ore 3 0 mi n utes , will be 
s u m marize d usi n g descri pti ve statistics a n d 9 5 % c o nfi de nce i nter vals.  
9. 4. 3  Sec o n d ar y E n d p oi nts  
9. 4. 3. 1  Sec o n d ar y E ffic ac y E n d p oi nt  
T he sec o n d ar y  efficac y  e n d p oi nt, plas ma gl uc ose c o nce ntr ati o n c ha n ge fr o m baseli ne at 
1 5  mi n utes after I M P i njecti o n or at t he ti me of resc ue b y I V gl uc os e if bef ore 1 5 mi n utes, will 
be s u m marize d usi n g des cri pti ve statistics.  
9. 4. 3. 2  P h ar m ac o ki netic E n d p oi nts  
T he f oll o wi n g P K para m eters will be esti mate d b y n o n -c o m part me ntal a nal ysis ( N C A) base d o n 
plas ma dasi gl uca g o n c o n ce ntrati o ns deri v e d fr o m 0 t o 3 0 0  mi n utes  a n d s u m marize d wit h 
descri pti ve statistics : 
•  A U C 0 -3 0 mi n 
•  A U C 0 -3 0 0 mi n 
•  A U C 0 -t 
•  A U C i nf 
•  C ma x  
•  T ma x  
•  λz  
•  t½  
•  C l/f 
•  Vz/f  
•  M R T  
9. 4. 3. 3  S afet y a n d T oler a bilit y E n d p oi nts  
Cli nic al L a b or at or y D at a  
Cli nical la b orat or y test res ults will be mar ke d w het her t he res ult is bel o w, wit hi n or a b o ve t he 
res pecti ve refere n ce ra n g e. T he n u m ber of val ues o utsi de of t he refere n ce ra n ge will be c o u nte d.  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 5 1 /7 8  
C O N FI D E N T I A L  
A E s 
A Es will be c o de d usi n g t he latest a vaila ble versi o n of t he Me dical Di cti o nar y f or Re g ul at or y 
Acti vities. All A Es will be liste d, h o we ver o nl y A Es t hat are c o nsi d ere d tr eat me nt e mer ge nt 
( A Es wit h an o nset ti me at or after t he i nitial d ose of trial dr u g) will be ta b ulate d. S uc h ta bles 
will i ncl u de t he c o u nts a n d perce nt a ges of patie nts e x perie n ci n g A Es b y s yste m or ga n class a n d 
preferre d t er m. If a patie nt has m ore t ha n 1  A E w hic h c o des t o t he sa me p referre d ter m, t he 
patie nt will be c o u nte d o nl y o nce f or t hat preferre d ter m. T he t otal n u m ber of e ve nts d oc u me nt e d 
per s yste m or ga n  class a n d preferre d t er m will als o be dis pla ye d.  
Ot her S afet y D at a  
A d mi nistrati o n a n d t i me t o first I V gl u c ose i nf usi o n, wit hi n 3 0  mi n utes  after I M P a d mi nistrati o n 
( N B: I V gl uc ose i nf usi o n pri or t o I M P a d mi nistrati o n s h o ul d n ot be i ncl u de d, as it is part of 
h y p o gl yce mic cla m p pr o ce d ure) will be descri be d wit h descri pti ve statistics . 
Vital si g ns, p h ysical e xa mi nati o n  res ults, E C G, a n d l ocal t olera bilit y data will be s u m marize d 
wit h descri pti ve statistics.  
I m m u n o ge nicit y 
Occ urre nce of A D A will be a nal yz e d descri pti vel y.  A D A a n d res ult fr o m ass ociate d 
c haracteri zati o n assa ys will be prese nte d  des cri pti vel y.  
C o nti n u o us Gl uc ose M o nit ori n g ( C G M)   
At V isit 2 , gl uc ose le vels will be m o nit ore d b y C G M . 
C G M data will be prese nte d gra p hicall y as i n di vi d ual pl ots of gl uc ose meas ure me nts o ver ti me 
fr o m t he ti me of st o p pi n g t he partici pa nt’s i ns uli n p u m p t o 3 0 0 mi n utes after dasi gl uca g o n  
a d mi nistrati o n . 
9. 5  I nteri m A n al ysis 
N o i nteri m a nal ysis is pla n ne d f or t his  trial. 
 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 5 2 /7 8  
C O N FI D E N T I A L  
1 0  S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L C O N SI D E R A TI O N S  
1 0. 1  A p pe n di x 1: Re g ul at o r 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 he cli nical trial a ut h ori zati o n gra nte d b y t he c o m pete nt a ut h orit y ( C A) a n d a fa v ora ble o pi ni o n 
fr o m t he rele v a nt I E C/I R B(s) will be o btai ne d pri or t o t he start of t he trial. T he l ocal a ut h orities 
will be n otifie d a b o ut t he trial as re q uir e d b y la w.  
T he C A a n d t he I E C/I R B will be n otifie d a b o ut t he e n d of t he tri al a n d a re p ort s u m marizi n g t he 
trial res ults will be se nt t o t he C A a n d t he I E C/I R B acc or di n g t o re p orti n g ti meli nes . If t he trial is 
ter mi nate d earl y, t he C A a n d t he IE C /I R B will be n otifie d wit hi n 1 5  da ys.  
T he I E Cs a n d/ or I R Bs meet t he re q uire me nts of t h e I nter n ati o nal C o u ncil f or Har m o nisati o n 
(I C H) Har m o nise d Tri partite G ui deli ne f or G o o d Cli nical Practice ( G C P ) E 6 ( R 2)  a n d l ocal 
le gislati o n. I R Bs als o meet t he re q uir e me nts of 2 1 C o de of Fe d eral Re g ulati o ns ( C F R)  5 6.  
T he trial will be c o n d uct e d i n acc or da nce wit h t he et hical pri nci ples set f ort h i n t he Declarati o n 
of Helsi n ki (i ncl u di n g a me n d me nts).  
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 t he s p o ns or wit h s ufficie nt, acc urate fi n a ncial 
i nf or mati o n as re q u este d t o all o w t he s p o ns or 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 he c o urse of t he trial a n d f or 
1  year after c o m pleti o n of t he trial. 
1 0. 1. 3  I nf or me d C o nse nt Pr ocess 
Writte n i nf or me d c o ns e nt will be o btai ne d fr o m t he pare nt (s)/le gal g uar dia ns  of all patie nts pri or 
t o e nr oll me nt i nt o t he trial. A d diti o nall y, t he c hil dre n will be i nf or me d a b o ut t he trial wit h age -
a p pr o priate i nf or mati o n materials, a n d t heir asse nt will be o btai ne d i n acc or da nce wit h l ocal 
re g ulati o ns. T he i n vesti g at or will e x plai n t o eac h patie nt a n d t heir pare nts/le gal g uar dia ns  orall y 
a n d i n writi n g ( patie nt i nf or mati o n s heet) t he n at ure, si g n ifica nce, ris ks, a n d i m plicati o ns of t he 
trial bef ore i n cl usi o n. I n partic ular, t he patie nts will be i nf or me d a b o ut t he f oll o wi n g: 
•  T heir c o nse nt is v ol u ntar y  
•  T he p ossi bilit y of wit h dra wi n g fr o m t he cli nical trial at a n y ti me b y re v o ki n g t he c o nse nt 
a n d with o ut a n y res ulti n g disa d va nta ge  
•  H o w pers o nal a n d healt h -relate d d ata will be c ollecte d a n d use d d uri n g t he trial 
•  C o nfi de ntialit y, ie , me dical rec or ds ma y be e x a mi ne d b y a ut h orize d m o nit ors or Cli nical 
Q ualit y Ass ura nce a u dit ors a p p oi nte d b y t he s p o ns or, b y  a p pr o pri ate I E C/I R B me m bers, 
a n d b y i ns pect ors fr o m re g ulat or y a ut h orities  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 5 3 /7 8  
C O N FI D E N T I A L  
All pare nts/le gal g uar di a ns  a n d t he c hil dre n will recei ve a c o p y of t h e res p ecti ve patie nt 
i nf or mati o n s heet a n d a c o p y of t heir si g ne d a n d d ate d i nf or me d c o nse nt/asse nt f or m. 
All patie nts will be i ns ure d a gai nst i nj ur y ca us e d b y t heir partici pati o n i n t he trial acc or di n g t o 
le gal re q uir e me nts. T he y will be i nf or me d a b o ut t h e i ns ura nce a n d t he res ulti n g o bli gati o ns o n 
t heir part. 
1 0. 1. 4  D at a Pr otecti o n  
Patie nt s will be assi g ne d a u ni q ue i de ntifier b y t he s p o ns or. A n y patie nt  rec or ds or datasets t hat 
are tr a nsferre d t o t he s p o ns or will c o ntai n t he i de ntifier o nl y; patie nt  na mes or a n y i nf or mati o n 
w hic h w o ul d ma ke t he p atie nt  i de ntifia ble will n ot be tra nsferre d. 
T he patie nt a n d t he p are nt(s)/le gal g uar dia n(s) m ust be i nf or me d t hat t he patie nt’s me dical 
rec or ds ma y b e e x a mi ne d b y Cli nical Q ualit y Ass ura nce a u dit ors or ot her a ut h orize d pers o n nel 
a p p oi nte d b y t he s p o ns or, i ncl u di n g rele va nt part ners, 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.  
1 0. 1. 5  C o m mittees Str uct ure  
Zeala n d P har m a A/ S is t he s p o ns or of t his trial. A desi g nate d  c o ntr act res earc h or ga nizati o n  
( C R O) will or ga nize t he perf or ma n ce of t his trial.  
A list wit h t he na mes a n d a d dresses of t he res p o nsi ble i nstit uti o ns a n d pers o ns is pr o vi de d i n 
A p pe n di x  5  of t his pr ot oc ol.  
1 0. 1. 5. 1  S afet y D at a Re vie w a n d C o m mittee  
S afet y C o m mittee  
A n i nter nal Zeala n d P har ma A/ S safet y c o m mittee is c o nstit ute d t o perf or m o n g oi n g bli n de d 
safet y s ur veilla n ce of cli nical trials wit h dasi gl uca g o n, i ncl u di n g t his trial. 
If safet y si g nals or c o ncer ns are o bs er ve d, w het her base d o n re p orte d S A Es, re vie w of all A Es 
a n d la b orat or y p ara m eters re p orte d, or a n y ot her n otificati o n of si g nifica nt fi n di n gs, t he safet y 
c o m mittee will res p o n d a p pr o priatel y t o pr otect t h e safet y of t h e patie nts.  
T he safet y c o m mittee c o n ve nes re g ul arl y, e ver y q uarter, t o re vie w t he s afe t y i nf or mati o n, 
i ncl u di n g S A Es, A Es , a n d la b orat or y dat a. A d diti o nal safet y c o m mittee m eeti n g ma y be calle d at 
t he discreti o n of a n y s afet y c o m mittee me m ber, s h o ul d ne w safet y si g nals o cc ur d uri n g t his ti me 
i nter val. 
Tri al S afet y Gr o u p  
I n a d diti o n, ne w patie nts will o nl y be d ose d after safet y assess m e nt of t he d osi n g visit f or t he 
prece di n g p atie nt is c o m plete d a n d assess e d b y t he Trial Safet y Gr o u p  ( T S G). T h us , e xce pt f or 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 5 4 /7 8  
C O N FI D E N T I A L  
t he first patie nt bei n g d os e d i n t he trial, i n vesti gat ors nee d writte n per missi o n (e g, via a n e mail)  
fr o m t he T S G c hair t o d ose a patie nt i n t he trial.  
T he T S G c o nsists of t he f oll o wi n g pers o n nel:  
•  Pri nci pal i n vesti gat or or his de p ut y  
•  Me dical res p o nsi ble of t h e s p o ns or (c h air)  
•  Cli nical trial ma na ger  a n d/ or cli nical p har mac ol o gist  of t he s p o ns or  
•  Safet y res p o nsi ble of t he s p o ns or ( p har mac o vi gila nce [ P V])  
•  Statisticia n of t he s p o ns or (a d -h o c me m ber)  
•  A re prese ntati ve fr o m t he part ner of t he s p o ns or (a d-h oc me m ber)  
T he pri nci pal i n vesti gat or f or t he site res p o nsi ble f or treat me nt of  t he patie nt bei n g assesse d ma y 
be i n vite d t o t he T S G meeti n g.  
T he T S G will re vie w  t he f oll o wi n g n o n -verifie d  d ata bef ore deci di n g if t he ne xt patie nt ca n b e 
d ose d : 
•  S afet y data (i n cl u di n g S A Es, A Es, c o nc o mita nt me dicati o n, l ocal t olera bilit y, vital si g ns, 
p h ysical e xa m)  a n d b o d y wei g ht data c ollecte d at Visit  1 a n d 2  
•  Safet y  data (sta n d ar d safet y 1 2-lea d E C G, l ocal t olera bilit y, bi oc he mistr y, a n d 
he mat ol o g y ) a n d a g e c oll ecte d at Visit 1    
•  Gl uc ose data d eri ve d fr o m t he gl uc os e a nal yzer c ollecte d at Visit  2  
•  D ose a d mi nist ere d ( 0. 3 m g or 0. 6 m g) 
•  I n case p h ar mac o ki netic ( P K ) data c ollecte d at Visit  2 is a vaila ble t o t he T S G  f or t he 
prece di n g p atie nt or ot her patie nts d ose d earlier , t hese data will als o be i n cl u de d i n t he 
re vie w. Re vie w of P K data is n ot a prere q uisite f or  deci di n g t o c o nti n ue d osi n g a ne w 
patie nt ; h o we ver, t he T S G ma y deci de t o a wait t h e P K data bef ore d eci di n g o n w het her a 
ne w patie nt  ca n be d ose d.  
T he T S G ma y deci d e t o pa use t he d osi n g of  f urt her patie nts a n d escalat e a n y si g nifica nt fi n di n gs 
t o t he C hair pers o n of t he Zeala n d P har m a A/ S ( Z P ) Safet y C o m mittee.  
D osi n g of t he ne xt patie nt will be pa use d if  a patie n t e x perie nces an  S A E j u d ge d as pr o ba bl y or  
p ossi bl y relate d t o dasi gl uca g o n . If t his occ urs, t h e T S G m ust n otif y t he C hair pers o n of t h e Z P 
Safet y C o m mittee. T he Z P Safet y C o m mittee will a p p oi nt a n assess or ( n ot ot her wise i n v ol ve d i n 
t he trial) f or e val uati o n of A E relati o ns hi p t o dasi gl uca g o n. T he c o n cl usi o n fr o m t his assess me nt 
will be c o m m u nicate d t o t he T S G, a n d base d o n t his assess me nt, t he T S G will deci de if d osi n g 
of t he ne xt patie nt ca n pr ocee d. T h e T S G ma y i ntr o d uce a d diti o nal preca uti o ns t o t he trial bef ore 
d osi n g of t he ne xt patie nt. T he i n vesti gat or m ust n ot  i nitiate d osi n g of t he ne xt patie nt u ntil 
per missi o n t o d o s o fr o m t he T S G has bee n o btai n e d  a n d t he d ose le vel ( 0. 6 m g or 0. 3 m g) f or 
t he ne xt d ose d patie nt  has bee n c o nfir m e d b y t he sp o ns or.  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 5 5 /7 8  
C O N FI D E N T I A L  
1 0. 1. 6  Pr ot oc ol D e vi ati o ns  
C o nti n u o us pr ot oc ol de viati o n ma na ge me nt i s part of t he m o nit ori n g acti vities a n d will be 
detaile d i n t he M o nit ori n g Pla n. Bef ore data are release d f or st atistical a nal ysis, a re vie w of all 
data will ta ke place t o i de ntif y pr ot oc ol de viati o ns t hat ma y p ote ntiall y affect t he res ults. 
S p uri o us o utliers will be assesse d . I n a d diti o n, pr ot oc ol de viati o ns t hat ma y p ote ntiall y affect t he 
res ults will be i de ntifie d a n d it will be assesse d if patie nts a n d/ or data s h o ul d be e xcl u de d fr o m 
t he a nal ysis. Pr ot oc ol de viati o ns will be classifie d as mi n or or maj or i n a c o nsiste nt wa y. Maj or 
de viati o ns fr o m t he pr ot o c ol ma y lea d t o t he e x cl usi o n of a patie nt fr o m t he per pr ot oc ol set. 
Maj or pr ot oc ol de viati o ns ma y i ncl u de de viati o ns relate d t o trial i ncl usi o n or e xcl usi o n criteria, 
c o n d uct of t he trial,  p atie nt ma na ge me nt or patie nt assess me nt. U nless e x pli citl y deci de d 
ot her wise d uri n g t he tr eat me nt -mas ke d data re vie w, t he f oll o wi n g will be c o nsi dere d maj or 
pr ot oc ol de viati o ns:  
•  Vi olati o n of o ne or m ore maj or i ncl usi o n/e xcl usi o n criteria  
•  I nterr u pti o n of a d mi nistrati o n of I M P 
•  Si g nifica nt de viati o n fr o m ti me wi n d o ws  
•  Missi n g pri mar y e n d p oi nt  
T he vi olati o n of se veral maj or i ncl usi o n/e xcl usi o n criteria or t h e c o m plete a bse nce of efficac y 
data mi g ht lea d t o e xcl usi o n of t he patie nt fr o m t h e f ull a nal ysis set . In t hat case, t he decisi o n 
s h o ul d be ta ke n at t he dat a re vie w m eeti n g, a n d t h e e xcl usi o n fr o m efficac y a nal ysis will be 
j ustifie d i n t he si g ne d n otes of t he meeti n g. 
O b vi o usl y err o ne o us dat a p oi nts ma y be e xcl u de d fr o m t he a nal yses or re -a nal yze d (i n case o f, 
f or e xa m ple, s er u m c o n ce ntrati o ns). T he d ecisi o n t o re-a n al yze or e xcl u de data p oi nts fr o m t he 
statistical a nal ysis is t he j oi nt res p o nsi bilit y of t he s p o ns or a n d t he trial statisticia n.  
T he patie nts or o bser vati o ns t o be e xcl u de d a n d t h e reas o n f or t he ir e xcl usi o n will be 
d oc u me nte d a n d si g ne d b y t h ose res p o nsi ble pri or t o data base releas e. T he d oc u me ntati o n will 
be st ore d t o get her wit h t he re mai ni n g trial d oc u me ntati o n. T he patie nts a n d o bser vati o ns 
e xcl u de d fr o m a nal ysis sets, a n d t he c orres p o n di n g re as o ns, will be des cri b e d i n t he cli nical trial 
re p ort. 
1 0. 1. 7  Pr ot oc ol C h a n ges  
T his trial pr ot oc ol ma y be a me n de d f oll o wi n g t he pr oce d ures s pecifi e d b y l ocal la ws a n d 
re g ulati o ns. S u bsta ntial a me n d me nts t o t his trial pr ot oc ol will o nl y be i m ple me nte d u p o n  
a p pr o val of t he C A(s) a n d a fa v ora ble o pi ni o n of t he et hics c o m mittee(s) h a ve bee n o btai ne d.  
S u bsta ntial a me n d me nts t o t he c o n d uct of t he cli nical trial ma y arise fr o m c ha n ges t o t he 
pr ot oc ol or fr o m ne w i nf or mati o n relati n g t o t he scie ntific d oc u me nts i n  s u p p ort of t he trial. 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 5 6 /7 8  
C O N FI D E N T I A L  
A me n d me nts t o t he trial are re gar de d as “s u bsta ntial” w here t he y are li kel y t o ha ve a si g nifica nt 
i m pact o n o ne of t he f oll o wi n g: 
•  T he safet y, p h ysic al healt h , a n d me ntal i nte grit y of t he patie nts  
•  T he scie ntific val u e of t h e trial  
•  T he  c o n d uct or m a na ge m e nt of t he trial  
•  T he q ualit y or safet y of a n y I M P use d i n t he trial  
If a ne w e ve nt o cc urs rel ate d t o t he c o n d uct of t h e trial or t he de vel o p me nt of t he i n vesti gati o nal 
pr o d uct, w hic h ma y affect t he safet y of t he patie nts, t he s p o ns or a n d t he i n v esti gat or will ta ke 
a p pr o priate s afet y meas ures t o pr otect t he p atie nts a gai nst a n y i m me diate hazar d. T he s p o ns or 
will i m me diatel y i nf or m t he C A(s) a n d et hics c o m mittee(s) of t he ne w e ve nt , a n d t he meas ures 
ta ke n. 
1 0. 1. 8  S o urce D oc u me nts  
S o urce  d oc u me nts pr o vi d e e vi de nce f or t h e e xiste n ce of t he p atie nt a n d s u bsta ntiate t he i nte grit y 
of t he data c ollecte d. S o urce d oc u m e nts are file d at t he i n vesti gat or’s site  a n d s h o ul d be 
attri b uta ble, le gi ble, c o nt e m p ora ne o us, ori gi nal, acc urat e, a n d c o m plet e . 
D ata e ntere d i n t he e C R F t hat are tr a nscri be d fr o m s o urce d oc u m e nts m ust be c o nsiste nt wit h t he 
s o urce d oc u m e nts or t he discre pa n cies m ust be e x plai ne d. T he i n vesti gat or ma y nee d t o re q u est 
pre vi o us me dical r ec or ds or tra nsfer rec or ds, de p e n di n g o n t he tr ial. Als o, c urre nt me dical 
rec or ds m ust be a vaila ble. 
F or C G M, t he defi niti o n of s o urce d ata f oll o ws t h e F o o d a n d Dr u g A d mi nistrati o n ( F D A ) 
G ui da nce o n Electr o nic S o urce Data i n Cli nical I n vesti gati o ns ( 2 0 1 3). 7 
T he i n vesti gat or m ust mai ntai n a de q uate a n d acc urate d oc u me ntati o n (s o urce data) t hat s u p p orts 
t he i nf or mati o n e ntere d i n t he eC R F.  
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 
eC R F b y a ut h orize d site pers o n nel are acc urate, c o m plete, a n d verifi a 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 patie nts are b ei n g pr ot ecte d; a n d t hat t he tri al 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 o c ol a n d a n y ot her tri al 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 uire me nts.  
1 0. 1. 9  Electr o nic C ase R e p ort F or ms  
All t he i nf or mati o n c ollecte d d uri n g t he trial will be rec or de d i n t he e C R Fs, w hic h are i d e ntifie d 
b y patie nt n u m b er. A desi g nate d C R O  will desi g n s uita ble e C R Fs. T he i n vesti gat or will e ns ure 
t hat t he e C R Fs are c o m pl ete d c orrectl y. T he i n v esti gat or will si g n all data e ntere d i n t he e C R F 
electr o nicall y, si g nif yi n g a gree m e nt wit h a n d res p o nsi bilit y f or t he rec or de d data . 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 5 7 /7 8  
C O N FI D E N T I A L  
1 0. 1. 9. 1  D at a Q u alit y C o ntr ol a n d Ass ur a nce  
T he i n vesti gat or will per mit trial -relate d m o nit ori n g, I E C r e vie w, a n d re g ulat or y i ns pecti o ns, 
pr o vi di n g direct access t o s o urce dat a/ d oc u me nts. S p o ns or -a ut h orize d q u alit y ass ura nce 
pers o n nel ma y carr y o ut a u dits f or w h ic h t he i n vesti gat or m ust pr o vi de s u p p ort. 
A m o nit or fr o m a desi g n ate d C R O  will s u per vise t he trial. T he trial m o nit or will c o ntact t he 
i n vesti gat or re g ularl y t o disc uss t he pr o gress of t h e trial a n d t o c hec k t he tri al d oc u me nts 
i ncl u di n g t he i nf or me d c o nse nt f or ms (I C Fs) f or c o m plete ness a n d c o nsiste nc y. 
T he trial m o nit or or a re prese ntati ve of t h e s p o ns or will cr oss -c h ec k t he dat a e ntere d i n t he 
e C R Fs wit h t he s o urce d ata at t he trial site a n d o bser ve t he trial pr oce d ures i n or der t o verif y 
a d here n ce t o t he trial pr ot oc ol.  
T he e C R Fs will be c h ec k e d f or c o m plet e ness a n d c orrect ness b y t he m o nit or a n d b y t he data 
ma na ge me nt de p art me nt of t he desi g nate d C R O  acc or di n g t o t he desi g nat e d C R O sta ndar d 
o perati n g pr oce d ures, a n d t he i n vesti gat or will res ol ve a n y q ueries.  
All of t he cli nical data will be ca pt ure d via electr o nic data ca pt ure ( E D C ) usi n g a we b -bas e d 
t o ol. T he s oft ware M ar vi n fr o m t he c o m pa n y X Cli nical ( w w w. x cli nical.c o m) is t he preferred 
E D C s oft ware. M ar vi n is c o m plia nt wit h all le gislati o n rele va nt t o E D C ( F D A  U S A, 2 1 C F R 
Part 1 1, G C P).  
T he i n vesti gat or site staff will e nter a n d e dit t he data via a sec ure n et w or k, wit h sec ure access 
feat ur es ( user na me a n d p ass w or d). A c o m plete electr o nic a u dit trail will be mai ntai ne d. T he 
i n vesti gat or will a p pr o ve t he data usi n g a n electr o nic si g nat ure ( Ref: 2 1 C F R Part 1 1), a n d t his 
a p pr o val is use d t o c o nfir m t he acc urac y of t he dat a rec or de d.  
T he e C R Fs will be use d f or all patie nts. T he i n vesti gat or ’s data will be accessi ble fr o m t he 
i n vesti gat or’s site t hr o u g h o ut t he trial. T he e C R Fs m ust be ke pt c urre nt t o reflect patie nt stat us at 
eac h p h ase d uri n g t he c o urse of t he trial. T h e e C R F will n ot ca pt ure p ers o nalize d data. T he 
i n vesti gat or m ust ma ke a se parat e c o nfi de ntial r ec or d of pers o nalize d det ails ( na me a n d i nitials) 
o n t he patie nt i de ntificati o n a n d e nr oll me nt l o g. T he i n vesti gat or d oes all c ha n ges t o data t hr o u g h 
t he E D C s yste m. 
It is t he res p o nsi bilit y of t he p ri nci pal in vesti gat or of t he res pec ti ve site t o e ns ure t hat all patie nt 
disc o nti n uati o ns or c ha n ges i n I M P or ot her me di cati o ns e ntere d i n t he patie nt’s me dical rec or ds 
are als o ma d e o n t he pati e nt’s  e C R F. 
T he e C R Fs f or a n y patie nt lea vi n g t he trial s h o ul d be c o m plete d at t he ti me of t he fi nal visit or 
s h ortl y t hereaft er. 
1 0. 1. 1 0  Disse mi n ati o n of Cli nic al Tri al D at a  
Disse mi nati o n of cli nical trial data a n d dat a ma na ge me nt will be perf or me d acc or di n g t o t he 
desi g nate d C R O ’s sta n dar d o perati n g pr o ce d ures. 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 5 8 /7 8  
C O N FI D E N T I A L  
1 0. 1. 1 1  Rete nti o n of T ri al R ec or ds  
T he i n vesti gat or m ust ret ai n rec or ds a n d d oc u me nts pertai ni n g t o t he c o n d u ct of t he trial a n d t he 
distri b uti o n of t he i n vesti gati o nal pr o d uct ( e g, I C Fs, la b orat or y sli ps, me dicati o n i n ve nt or y 
rec or ds a n d ot her p erti ne nt i nf or mati o n) acc or di n g t o l ocal re q uire me nts. 
T o meet re g ulat or y re q uire me nts, t he e C R F d ata will be electr o nicall y st ore d at sites. T he C DI S C 
O D M (see htt p:// w w w.c disc. or g/ f or details) will b e use d t o st ore a n d arc hi v e all electr o ni c data 
at t he sites. Si nce C DI S C O D M is als o t he s o urce f or t he E D C we b -base d s yste m, n o 
tra nscri pti o n of data is necessar y. C DI S C O D M is a platf or m-i n de pe n de nt sta n dar dize d d ata 
f or mat i ncl u di n g t he c o m plete trial meta data a n d a u dit trail. T he data ca n b e re vie we d at a later 
sta ge usi n g off-t he-s helf t o ols. C DI S C pro vi des a c o m plete C DI S C O D M Vie wer f or t hese 
p ur p oses. If nee de d, P D F files ca n be create d fr o m t he O D M file.  
After trial c o m pleti o n at sites i n t he U S, t he i n vesti gat or will retai n a n d preser ve 1  c o p y of all 
data ge nerate d i n t he c o urse of t he trial, s pe c ificall y i ncl u di n g, b ut n ot li mite d t o, t h ose defi ne d 
b y G C P as esse ntial u ntil:  
•  At least 2  years after t h e last mar keti n g a ut h orizati o n f or t he I M P has bee n a p pr o ve d or 
t he s p o ns or has disc o nti n ue d its researc h wit h t he I M P, or 
•  At least 2  years h a ve el a pse d si nce t he f or mal disc o nti n uati o n of cli nical d e vel o p me nt of 
t he I M P 
H o we ver, t hese d oc u m e nts s h o ul d be retai ne d f or a l o n ger peri o d  ( 2 5 years after t he e n d of trial 
if data will be a part of an  E U s u b missi o n)  if re q uire d b y t he a p plica ble re g ulat or y re q uire m e nt(s) 
or if nee d e d b y t he s p o ns or.  
At t he e n d of s uc h p eri o d, t he i n vesti gat or will n otif y t he s p o ns or i n writi n g of his or her i nte nt t o 
destr o y all s uc h materi al. T he s p o ns or will ha ve 3 0  da ys t o res p o n d t o t he i n vesti gat or’s n otice , 
a n d t he s p o ns or will ha ve a f urt her o p p ort u nit y t o retai n s uc h materials at t he s p o ns or’s e x p e nse.  
1 0. 1. 1 2  Tri al  a n d Site St art a n d Cl os ure  
First Act of Recr uit me nt  
T he trial start date is t he date o n w hic h t he cli nical trial will be o pe n f or recr uit me nt of patie nt s. 
T he first act of recr uit me nt is t he first site o pe n a n d will be t he trial start date. 
Tri al / Site Ter mi n ati o n 
T he s p o ns or res er ves t he ri g ht t o m o dif y or ter mi nate  t he trial at a n y ti me. P ossi ble reas o ns f or 
ter mi nati o n are: 
•  Safet y reas o ns –  t he i nci de nce of A Es i n t his or a n y ot her trial usi n g t he sa me I M P 
i n dicates a p ote ntial healt h ris k f or t he patie nts 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 5 9 /7 8  
C O N FI D E N T I A L  
•  Ne w scie ntific k n o wle d g e bec o mes k n o w n t hat ma kes t he o bjec ti ves of t he trial n o l o n ger 
feasi ble/ vali d 
•  U nsatisfact or y e nr oll me nt of patie nts  
A n y site ca n be cl ose d , a n d t he trial ter mi nate d f or t he f oll o wi n g reas o ns:  
•  T he site is u nli kel y t o be a ble t o recr uit s ufficie nt patie nts wit hi n t he a gree d ti me fra me 
•  T he site d oes n ot res p o n d t o trial ma na ge me nt re q uests  
•  Re peat pr ot oc ol vi olati o ns  
H o we ver, e ve n i n case of site disc o nti n uati o n t he site s h o ul d be ke pt o pe n as l o n g as pre vi o usl y 
e nr olle d patie nts are o n g oi n g. Patie nts alrea d y e nr olle d s h o ul d be f oll o we d a n d d oc u me nte d f or 
t heir e ntire i n di vi d ual trial d urati o n bef ore act uall y disc o nti n ui n g t he site. 
T he i n vesti gat or ma y i nitiate trial 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. 
If t he trial is pre mat urel y ter mi nate d or s us pe n de d, t he s p o ns or s hall pr o m ptl y i nf or m t he 
i n vesti gat ors, t he I E Cs/I R Bs, t he re g ulat or y a ut h orities, a n d a n y c o ntr act r esearc h or ga ni zati o n(s) 
use d i n t he trial of t he reas o n f or ter mi nati o n or s us pe nsi o n, as s pecifie d b y t he a p plica ble 
re g ulat or y re q uire me nts. T he i n vesti gat or s hall pr o m ptl y i nf or m t he patie nt ’s pare nt(s)/le gal 
g uar dia n (s) a n d s h o ul d ass ure a p pr o priate patie nt  t hera p y a n d/ or f oll o w-u p . 
1 0. 1. 1 3  P u blic ati o n P olic y  
T he i nf or mati o n o btai ne d d ur i n g t he c o n d uct of t his trial is c o nsi dere d c o nfi de ntial a n d will be 
use d b y or o n be half of Z eala n d P har ma A/ S f or re g ulat or y p ur p oses as w ell as f or t he ge n eral 
de vel o p me nt of t he I M P. All i nf or mati o n s u p plie d b y Zeala n d P har m a A/ S i n c o n necti o n wit h 
t his trial will re mai n t he s ole pr o pert y of Z eala n d P har ma A/ S 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 will be discl ose d t o ot hers wit h o ut pri or writte n c o nse nt fr o m 
Zeala n d P har m a A/ S. S uc h i nf or mati o n  will n ot be use d e xce pt i n t he perf or ma nce 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 p h ysicia ns w h o are 
c o n d ucti n g ot her cli nical trials wit h t he I M P, if dee me d necessar y b y Z eala n d P har ma A/ S. 
Pr o vi de d t hat certai n c o n diti o ns are f ulfille d, Zeal a n d P har ma A/ S 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 h ers w h o re q uire access f or researc h pr oj ects 
st u d yi n g t he sa me diseas e a n d/ or I M P st u die d i n t his trial. 
O ne i n vesti gat or will be a p p oi nte d t o re vie w a n d si g n t he cli nical trial re p ort (si g nat or y 
i n vesti gat or) o n be half of all partici pati n g i n vesti gat ors. 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 6 0 /7 8  
C O N FI D E N T I A L  
C o m m u nic ati o n of R es ults  
N o per missi o n t o p u blis h will be gra nte d t o a n y c o ntract res earc h or ga ni zati o n ( C R O ) i n v ol ve d 
i n t he trial. 
T he res ults of t his trial will be patie nt  t o p u blic discl os ure o n e xter nal we bsites acc or di n g t o 
i nter nati o nal a n d nati o nal re g ulati o ns. 
Zeala n d P har m a A/ S reser ves t he ri g ht t o defer t he releas e of data u ntil s pecifie d milest o nes a re 
reac h e d, f or e xa m ple w h e n t he cli nical trial r e p ort is a vaila ble. T his i ncl u des t he ri g ht n ot t o 
releas e t he res ults of i nteri m a nal yses beca use t he releas e 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 tri al. 
At t he e n d of t he trial, o n e or m ore sci e ntific p u blicati o ns (i ncl u di n g a bstracts, p osters , a n d 
prese ntati o ns) ma y b e pre pare d c olla b orati vel y b y t he i n vesti gat or(s) a n d Z eala n d P har ma A/ S. 
Zeala n d P har m a A/ S 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 otect i ntelle ct ual pr o pert y. I n all cas es, t he trial res ults will be re p orte d i n a n 
o bjecti ve, acc urat e a n d b ala nce d m a n ner. I n t he e ve 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 Zeala n d P har ma A/ S will be fairl y a n d 
s ufficie ntl y re prese nte d i n t he p u blicati o n. 
A ut h ors 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 U nif or m Re q uire me nts of t he 
I nter nati o nal C o m mittee of Me dical J o ur n al E dit ors. 
 
 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 6 1 /7 8  
C O N FI D E N T I A L  
1 0. 2  A p pe n di x 2: Cli nic al L a b or at or y Tests  
R o uti ne safet y la b orat or y tests will be perf or me d ce ntrall y. Sa m ples f or safet y la b orat or y 
para meters will be c ollecte d at Visits  1 a n d 3. T he f oll o wi n g para meters will be deter mi ne d:  
•  Cli nical c he mistr y  (meas ure d i n ser u m): s o di u m, p otassi u m, calci u m, creati ni ne, t otal 
bilir u bi n, A S T, A L T . If ad diti o nal cli nical c he mistr y para m eters are a n al yze d a n d 
re p orte d as part of a sta n dar d c he mistr y  pa n el , t hese data will als o be e v al u ate d .   
•  He mat ol o g y  ( meas ur e d i n w h ole bl o o d) : he m o gl o bi n, platelet c o u nt (t hr o m b oc ytes), t otal 
w hite bl o o d cell c o u nt (le uc oc ytes) . If a d diti o nal h e mat ol o g y para met ers are a nal yze d 
a n d re p ort e d as part of a sta n dar d he mat ol o g y  pa n el, t hese data will als o be e val uate d.   
•  P har mac o ki netic ( P K ) s a m ples ( meas ure d i n plas ma): P K assess me nts fr o m sa m ples 
c ollecte d d uri n g Visit  2 will be a nal yze d b y Y or k Bi oa nal ytical S ol uti o ns ( Y or k, U nite d 
Ki n g d o m).  
•  I m m u n o ge nicit y: Ser u m sa m ples f or assess me nt of a nti b o dies a gai nst dasi gl uca g o n will 
be meas ur e d at scree ni n g Visit  1 a n d at f oll o w -u p Vi sit 3 b y t he s pecial la b orat or y, Y or k 
Bi oa nal ytical S ol uti o ns ( Y or k, U nite d Ki n g d o m). T he cell -b ase d ne utr alizi n g a nti b o d y 
a nal yses will be perf or m e d b y a s peci al la b orat or y, Bi o A gil yti x, D ur ha m, N ort h Car oli na, 
U S A. A descri pti o n of t h e sa m ple ha n dli n g a n d sa m ple pr ocessi n g, st ora ge , a n d s hi p me nt 
at t he site will be i ncl u de d i n t he la b orat or y ma n u al. I m m u n o ge ni cit y sa m ples  are 
pla n ne d t o  be a n al yze d after t he last patie nt’s Visit 3 . 
•  T he cli nical a nti-dr u g a nti b o d y ( A D A ) ass a y s ha v e  bee n v ali date d i n acc or d a nce wit h 
e xisti n g g ui deli nes a n d rec o m me n dati o ns.  
•  C o nfir me d p ositi ve a nti -dasi gl uca g o n a nti b o d y sa m ples fr o m treat me nt -i n d uce d or 
treat me nt-b o oste d (titer i ncreas e a b o v e 4 -f ol d) A D A-p ositi ve patie nts will be assesse d f or 
bi n di n g titer, ne utralizi n g p ote nt ial a n d ne utralizi n g titer as well as cr oss-reacti vit y 
t o war ds e n d o ge n o us gl u ca g o n. A n y treat me nt-i n d uce d or treat me nt-b o oste d 
A D A -p ositi ve patie nts will be m o nit ore d as l o n g as o utc o mes relate d t o A D As are 
detecte d  or u ntil t he A D A le vel has ret ur ne d t o b aseli ne . 
A d diti o nal tests ma y be perf 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 ocal re g ulati o ns. C o nsi derati o n s re g ar di n g t he a d diti o nal bl o o d 
v ol u me re q uire d f or t he t ests s h o ul d be ma de pri or t o perf or mi n g a d diti o nal tests, ta ki n g t he 
c hil d’s b o d y wei g ht a n d esti mate d t otal bl o o d v ol u me (t otal esti mate d bl o o d v ol u me is 7 5  t o 
8 0  m L / k g) i nt o acc o u nt (refer t o Secti o n 6. 5. 3 ).  
 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 6 2 /7 8  
C O N FI D E N T I A L  
1 0. 3  A p pe n di x 3: A d verse E ve nts  a n d Seri o us  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 v al u ati n g, F oll o w -u p, a n d Re p orti n g  
Ti mel y , acc urate, a n d c o m plete re p orti n g a n d a nal ysis of safet y i nf or mati o n fr o m cli nical trials 
are cr ucial f or t he pr otecti o n of t he patie nts . In vesti gat ors, a n d t he s p o ns or are ma n date d b y 
re g ulat or y a g e ncies w orl d wi de t o re p ort safet y i nf or mati o n. 
1 0. 3. 1  Defi niti o n of A d verse E ve nt  
A n a d vers e e ve nt ( A E ) is a n y u nt o war d me dical o cc urre nce i n a cli nical tri al patie nt , te m p orall y 
ass ociate d wit h t he use of trial i nter ve nti o n, w het h er or n ot c o nsi dere d relat e d t o t he trial 
i nter ve nti o n. A n A E ca n t heref ore be a n y u nfa v ora ble a n d u ni nte 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 disease ( ne w or e xacer bate d) t e m p orall y ass ociate d 
wit h t he trial i nter ve nti o n. 
N ote: T his i ncl u des e ve nts fr o m t he first trial -rel ate d acti vit y after t h e patie nt has si g ne d t he  
i nf or me d c o nse nt. 
E ve nts Meeti n g t he A E Defi niti o n  
•  A cli nicall y si g nifica nt w orse ni n g of a c o nc o mita nt ill ness  
•  A cli nical la b orat or y a b n or malit y t hat is cli nicall y si g nifica nt, ie, a n y a b n or malit y t hat 
s u g gests a disease a n d/ or or ga n t o xicit y a n d is of a se verit y t hat re q uir es acti ve 
ma na ge me nt. A cti ve ma na ge me nt i ncl u des acti ve treat me nt or f urt her i n vesti gati o ns, f or 
e xa m ple c h a n ge of me di ci ne d ose or m ore fre q ue nt f oll o w -u p d ue t o t he a b n or malit y  
•  H y p o gl yce mic e pis o des (see Secti o n  8. 3. 6 ) 
•  I nje cti o n site reacti o ns 
•  Ne w c o n diti o ns detect e d or dia g n ose d after trial i nter ve nti o n a dmi nistrati o n e ve n t h o u g h 
it ma y ha ve bee n prese nt bef ore t h e start of t he tri al 
•  Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d i nter v e nti o n - i nter ve nti o n 
i nteracti o n 
•  Lac k of effic ac y will n ot be re p ort e d as a n A E or S A E. S uc h i nsta nces will be ca pt ur e d i n 
t he effic ac 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 will be re p orte d as A E or S A E if t he y f ulfill t he defi niti o n 
of a n A E or S A E  
E ve nts N O T Meeti n g t he A E Defi niti o n  
•  Pre -pla n ne d pr oce d u re, u nless t he c o n diti o n f or w hic h t he pr oce d ure was pla n ne d has 
w orse ne d fr o m t he first trial -relate d acti vit y after t he patie nt has si g ne d t he i nf or me d 
c o nse nt . 
•  Pre -e xisti n g c o n diti o ns, i ncl u di n g t h ose f o u n d beca use of scree ni n g pr oce d ures 
( pre-e xisti n g c o n diti o ns s h o ul d be re p orte d as me dical hist or y or c o nc o mita nt ill ness). 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 6 3 /7 8  
C O N FI D E N T I A L  
•  A n y cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs or ot her a b n or mal s afet y 
assess me nts w hic h are ass ociate d wit h t he u n derl yi n g disease, u nless j u d ge d b y t he 
i n vesti gat or t o be m ore s e vere t h a n e x pecte d f or t he patie nt ’s c o n diti o n. 
•  Sit uati o ns i n w hic h a n u nt o war d me dical o cc urre n ce di d n ot occ ur (s ocial a n d/ or 
c o n ve nie nce a d missi o n t o a h os pital).  
•  A ntici pate d da y -t o-d a y fl uct uati o ns of pre -e xisti n g disease(s) or c o n diti o n(s) pre se nt or 
detecte d at t he start of t h e trial t hat d o n ot w orse n. 
1 0. 3. 2  Defi niti o n of S A E  
A n S A E is d efi ne d as an y S A E  that, at an y d ose:  
•  Res ults i n deat h  
•  Is life t hreat e ni n g 
o  T he ter m “life t hr eate ni n g” i n t he defi niti o n of “seri o us” refers t o a n e ve nt i n w hic h 
t he patie nt  was at ris k of deat h at t he ti me of t he e ve nt. It d o es n ot refer t o a n e ve nt, 
w hic h h y p ot heticall y mi g ht ha ve ca us e d deat h, if it were m or e se vere.  
•  Re q uires i n patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os p italizati o n 
o  I n g e neral, h os pitalizati o n si g nifies t hat t he patie nt  has bee n a d mitte d ( us uall y 
i n v ol vi n g at least a n o ver ni g ht sta y) at t he h os pital or e mer g e nc y war d f or 
o bser vati o n a n d/ or tr eat me nt t hat w o ul d n ot ha ve bee n a p pr o priate i n t he p h ysicia n’s 
o ffice or o ut p atie nt setti n g. C o m plicati o ns t hat occ ur d uri n g h os pitalizati o n are A Es. 
If a c o m plic ati o n pr ol o n gs h os pitalizati o n or f ulfills a n y ot her seri o us criteri a, 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 pitalizati o n” occ urre d or was 
nec essar y, t he A E s h o ul d be c o nsi dere d seri o us.  
o  H os pitalizati o n f or ele cti ve treat me nt of a pre -e xisti n g c o n diti o n t hat di d n ot w orse n 
fr o m baseli ne is n ot c o nsi dere d a n A E. 
•  Res ults i n persiste nt or si g nifica nt disa bilit y/i nca pacit y  
o  T he ter m disa bilit y mea 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.  
o  T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie n ces of relati vel y mi n or me dical 
si g nifica nce s uc h as u nc o m plicate d hea dac he, n a usea, v o miti n g, diarr hea, i nfl ue nza, 
a n d acci de ntal 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.  
•  Is a c o n ge nital a n o mal y/ birt h defect 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 6 4 /7 8  
C O N FI D E N T I A L  
•  Is me di call y i m p orta nt. Me dical or scie ntifi c j u d g me nt s h o ul d be e xercise d b y t he 
i n vesti gat or 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 s uc h as 
si g nifica nt me dical e ve nts t hat ma y je o par dize t he patie nt  or ma y re q uir e m e dical or  
s ur gical i nter ve nti o n t o pre ve nt o ne of t he ot her o utc o mes liste d i n t he a b o ve defi niti o n. 
T hese e v e nts s h o ul d us uall y be c o nsi dere d seri o us.  
o  E xa m ples of s uc h e v e nts i ncl u de i n vasi ve or mali g na nt ca ncers, i nte nsi ve treat me nt 
f or aller gic br o nc h os pas m, bl o o d d yscrasias, c o n v ulsi o ns or de vel o p me nt of 
i nter ve nti o n de pe n de n c y or i nter ve nti o n a b use. 
Assess m e nt of I nte nsit y  
T he ma xi m u m i nte nsit y (se verit y) of all A Es m ust be assess e d b y t he i n v esti gat or a n d 
d oc u me nte d  fr o m t he first re p orti n g of t he A E.  
•  Mil d: N o or tra nsie nt s y m pt o ms, n o i nterfere nce wit h t he patie nt´s dail y acti vities  
•  M o derate: Mar ke d s y m pt o ms, m o derate i nterfere n ce wit h t he patie nt´s dail y acti vities  
•  Se vere: C o ns i dera bl e i nterfere nce wit h t he patie nt´s dail y acti vities, w hic h t he patie nt 
fi n ds u nacce pta ble. A se vere reacti o n d oes n ot necessaril y dee m t he A E as seri o us, a n d 
a n S A E is n ot al wa ys se v ere i n nat ure.  
Assess m e nt of C a us alit y  
Ca usalit y relati o ns hi p t o I M P 
•  Pr o ba ble: G o o d reas o n a n d s ufficie nt d oc u me ntati o n t o ass u me a ca us al rel ati 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 eti ol o g y ot her t ha n t he I M P 
O utc o me of a n A E  
•  Rec o vere d/ res ol ve d: T he patie nt has f ull y rec o v ere 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 ve d at t he first trial-relat e d acti vit y after t he 
patie nt ’s pare nt(s)/le gal g uar dia n(s) si g n e d t he i nf or me d c o nse nt. 
•  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 he patie nt is e x pecte d t o rec o v er 
fr o m t he e ve nt. 
•  Rec o vere d/res ol ve d wit h se q uelae: T h e patie nt has rec o vere 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 ue l 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 v e d: T he c o n diti o n of t he patie nt has n ot i m pr o ve d , a n d t he 
s y m pt o ms are u nc ha n ge d. 
•  Fatal: T his ter m is o nl y a p plica ble if t he patie nt di e d fr o m a c o n diti o n relat e d t o t h e 
re p orte d A E. O utc o mes of ot her re p orte d A Es i n a patie nt bef ore he/s he die d s h o ul d be 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 6 5 /7 8  
C O N FI D E N T I A L  
assesse d as "rec o vere d/r es 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 uelae" or " n ot rec o vere d/ n ot res ol ve d". A n A E wit h fatal o utc o me m ust be re p ort e 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 patie nt is l ost t o f oll o w -u p . 
S us pecte d U ne x pecte d S eri o us A d verse R e a cti o ns  
A n A E is c o nsi dere d a s us pecte d u ne x p ecte d s eri o us a d verse reacti o n if t he nat ure or se v erit y is 
n ot c o nsiste nt wit h t he a p plica ble pr o d uct Refere n ce Safet y I nf or mati o n. F or dasi gl uca g o n, t he 
e x pecte d n ess of a n A E will be deter mi ne d b y w het her or n ot it is liste d i n t he Refere nce Safet y 
I nf or mati o n secti o n of t h e IB . 
1 0. 3. 3  C ollecti o n, R ec o r di n g , a n d R e p orti n g of A E s 
All A Es, w het her seri o us or n o n -seri o us, will be c ollecte d  fr o m t he first trial-relat e d acti vit y after  
a si g ne d a n d date d I C F is o btai ne d u ntil t he e n d of t he p ost-treat me nt f oll o w-u p peri o d ( w hic h 
ma y i ncl u de c o nta cts f or f oll o w -u p of safet y). I n a d diti o n , patie nts will be o bser ve d f or a n y si g ns 
or s y m pt o ms a n d as ke d a b o ut t heir c o n diti o n b y o pe n q uesti o ni n g, s uc h as “ H o w ha v e y o u bee n 
feeli n g si nce y o u w ere l ast as ke d?” at eac h c o ntact wit h t he trial site ( visit or tele p h o ne). Patie nts 
will als o be e nc o ur a ge d t o s p o nta ne o usl y re p ort A Es occ urri n g at a n y ot her ti me d uri n g t he trial.  
All A Es, re gar dl ess of seri o us ness, se verit y, or pres u me d relati o ns hi p t o I M P, m ust be rec or de d 
a n d e val uat e d b y t he i n vesti gat or. W he ne v er p ossi ble, dia g n oses s h o ul d be gi ve n w he n si g ns a n d 
s y m pt o ms are d ue t o a c o m m o n eti ol o g y. If n o dia g n osis ca n be ma de, t h e i n vesti gat or s h o ul d 
rec or d eac h si g n a n d s y m pt o m as i n di vi d ual A Es. I n v esti gat ors m ust rec or d t heir o pi ni o n 
c o ncer ni n g t he relati o ns hi p of t he A E t o t he I M P. All meas ures re q uire d f or A E ma na g e me nt 
m ust be rec or de d i n t he s o urce d oc u m e nt a n d re p orte d acc or di n g t o s p o ns or i nstr ucti o ns.  
Eac h A E m ust be re p orte d o n t he A E pa ge of t he e C R F.  
All A E i nf or mati o n s h o ul d at a mi ni m u m i ncl u de t he f oll o wi n g:  
•  Date a n d ti me of o ns et a n d res ol uti o n  
•  Date a n d ti me of i n vesti g at or’s first i nf or mati o n o n t he A E  
•  Seri o us ness  
•  Se verit y  
•  Ca usal relati o ns hi p wit h I M P 
•  Meas ures ta k e n d ue t o A E  
•  Date a n d ti me of res ol uti o n a n d fi nal o utc o me  
1 0. 3. 4  F oll o w -u p of A E s 
All A Es t hat are o n g oi n g at t he e n d o f t he p atie nt’s partici pati o n i n t he trial will be f oll o we d u p 
u ntil t he e ve nt is res ol ve d or reac hes a s atisfact or y o utc o me as dee m e d b y t he i n vesti gat or.  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 6 6 /7 8  
C O N FI D E N T I A L  
F oll o w -u p acti o ns f or all S A Es will be perf or me d acc or di n g t o a p pr o priate cli nical care practices 
a nd ma y de pe n d o n t h e n at ure of t he e ve nt. T hes e will be deter mi ne d after i nter nal re vi e w a n d/ or 
s p o ns or re vie w. 
T he f oll o w -u p i nf or mati o n s h o ul d o nl y i ncl u de ne w ( u p date d a n d/ or a d diti o nal) i nf or mati o n t hat 
reflects t he sit uati o n at t he ti me of t he i n vesti gat or’s si g nat ure.  
F oll o w -u p i nf or mati o n o n ( S) A Es a n d A E SIs will be u p date d usi n g t he ( S) A E f or m. If a n o n -
seri o us e ve nt be c o mes seri o us d uri n g t he f oll o w-u p, it s h o ul d be re p orte d o n a n S A E f or m 
f oll o win g t he S A E  re p orti n g ti meli nes. 
T he i n vesti gat or m ust f or war d f oll o w-u p i nf or mati o n o n S A Es a n d if pre vi o usl y n o n -seri o us A Es 
bec o me S A Es t o t he s p o ns or i m me diatel y ( wit hi n 2 4  h o urs) after o btai ni n g k n o wle d ge a b o ut t he 
ne w i nf or mati o n.  
T he i n vesti gat or m ust rec or d f oll o w -u p i nf or mati o n i n t h e e C R F f or n o n -s eri o us A E a n d o n t he 
S A E f or m f or S A Es a n d A E SI. F oll o w -u p q uesti o ns t o i n vesti gat ors re gar di n g S A Es are q ueri e d 
directl y b y safet y C R O t o t he i n vesti gat or.  
F oll o w -u p i nf or mati o n m ust be re p orte d acc or di n g t o t he f oll o wi n g:  
•  S A Es  a n d A E SI: A ll S A Es a n d A E SI m ust be f oll o we d u ntil t he o utc o me of t he e ve nts is 
“rec o v ere d/res ol ve d, ” “rec o vere d/res ol ve d wit h se q uelae,” or “fatal,” a n d u ntil all q ueries 
ha ve bee n res ol ve d. Cas es of c hr o nic c o n diti o ns, ca ncer, or A Es t hat are o n g oi n g at ti me 
of dea t h ( w h ere d eat h is d ue t o a n ot her A E) ma y be cl ose d wit h t he o utc o me 
“rec o v eri n g/res ol vi n g” or “ n ot rec o vere d/ n ot res ol ve d” . Cases ca n be cl os e d wit h t he 
o utc o me of “rec o v eri n g/r es ol vi n g” w he n t he patie nt has c o m plete d t he f oll o w -u p peri o d 
a n d is e x pecte d b y t h e i n vesti gat or t o rec o v er.  
•  N o n -seri o us A Es: N o n-s eri o us A Es m ust be f oll o we d u ntil t he o utc o me of t he e ve nt is 
“rec o v eri n g/res ol vi n g,” “rec o vere d/r es ol ve d,” or “rec o vere d/r es ol ve d wit h se q uelae” or 
u ntil t he e n d of t he f oll o w -u p peri o d state d i n t he p r ot oc ol, w hic he ver c o m es first, a n d 
u ntil all q ueries relate d t o t hese A Es ha v e bee n res ol ve d. Cases of c hr o nic c o n diti o ns, 
ca ncer, or A Es t h at are o n g oi n g at ti me of deat h ( w here d eat h is d ue t o a n ot her A E) ma y 
be cl ose d wit h t he o utc o me of “rec o veri n g/re s ol vi n g” or “ n ot rec o vere d/ n ot res ol ve d.” 
Cases ca n be cl ose d wit h t he o utc o me of “rec o v eri n g/res ol vi n g” w he n a p atie nt has 
c o m plete d t he f oll o w -u p peri o d a n d is e x pecte d b y t he i n vesti gat or t o rec o v er.  
T he i n vesti gat or m ust e ns ure t hat t he w orst -case s e verit y a n d seri o us ness of a n e ve nt is ke pt 
t hr o u g h o ut t he trial, ie, if t he se verit y of a n A E c h a n ges o ver ti me, t he n it s h o ul d be re p orte d as 
1  A E wit h t he m ost se verit y. A w orse ni n g of a n u nres ol ve d treat me nt-e mer ge nt A E m ust be 
re p orte d as f oll o w-u p wit h re-ass ess me nt of se verit y a n d/ or seri o us ness of t he e ve nt.  F or A Es 
wit h o nset bef ore I M P a d mi nistrati o n, a n y w orse ni n g of se verit y/seri o us ness after I M P 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 6 7 /7 8  
C O N FI D E N T I A L  
a d mi nistrati o n s h o ul d be rec or de d as a s e parate A E, wit h t he o nset date of t he e ve nt 
c orres p o n di n g t o t he dat e of t he se verit y/seri o us n ess u p gra de.  
If a n A E is r es ol ve d a n d re-a p p ears l ater t he n it s h o ul d be re p orte d as a ne w A E.  
Q ueries or f oll o w -u p re q uests m ust be res p o n de d wit hi n 1 4  cale n dar da ys fr o m t he date of 
recei pt of t h e re q u est, u nless ot her wise s pecifie d i n t he f oll o w-u p re q u est.  
 
 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 6 8 /7 8  
C O N FI D E N T I A L  
1 0. 4  A p pe n di x 5 : A b bre vi ati o ns a n d Defi niti o ns 
A b bre vi ati o n  Defi niti o n  
A D A  
a nti-dr u g a nti b o dies  
A E  
a d verse e ve nt  
A E SI  
a d verse e ve nt of s p ecial i nterest  
A L T  
ala ni ne a mi n otra nsf eras e  
A S T  
as partate a mi n otra nsferas e  
A U C  
area u n d er t he pl as ma c o nce ntrati o n  vers us ti me c ur ve 
C A  
c o m pete nt a ut h orit y(ies)  
C F R  
C o de of Fe d eral Re g ulati o ns  
C G M  
c o nti n u o us gl uc ose m o nit ori n g  
C l/ F 
a p pare nt cleara nce (c orrecte d f or bi oa v aila bilit y)  
C ma x  
ma xi m u m o bser ve d c o nce ntrati o n  
C R O  
c o ntract r esearc h or ga nizati o n  
E C G  
electr ocar di o gra m  
e C R F 
electr o nic case re p ort f or m  
E D C  
electr o nic d ata ca pt ure  
F A S  
f ull a nal ysis set 
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
G C P  
G o o d Cli nical Practice  
I B 
I n v esti gat or’s Br oc h ure 
I C F 
i nf or me d c o nse nt f or m 
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n 
I E C 
i n de pe n de nt et hics c o m mittee 
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 V 
intra ve n o us (l y) 
M R T  
mea n resi de n ce ti me  
P D  
p har mac o d y n a mic(s)  
P K  
p har mac o ki netic(s)  
P T  
preferre d t er m  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 6 9 /7 8  
C O N FI D E N T I A L  
A b bre vi ati o n  Defi niti o n  
S A E  
seri o us a d vers e e v e nt 
S A F  
safet y a n al ysis set 
S A R S -C o V -2  se vere ac ute res pirat or y s y n dr o me c or o na vir us 2 
S C  
s u bc uta ne o us(l y) 
S D  
sta n dar d de viati o n 
S o A  
S c he d ule of A ssess me nts 
T 1 D  
ty pe  1 dia betes  
U L N  
u p per li mit of n or mal  
U S/ U S A  
U nite d States of A merica  
V z/f 
v ol u me of distri b uti o n of plas ma dasi gl uca g o n  
 
P h ar m ac o ki netic  a n d P h ar m ac o d y n a mic  A b bre vi ati o ns  
A b bre vi ati o n  Defi niti o n  
λ z 
ter mi nal rate c o nst a nt 
A U C 0 -1 5 mi n  
area u n d er t he pl as ma c o nce ntrati o n  vers us ti me c ur ve fr o m a d mi nistrati o n t o 
1 5  mi n utes  
A U C 0 -3 0 mi n  
area u n d er t he pl as ma c o nce ntrati o n  vers us ti me c ur ve fr o m a d mi nistrati o n t o 
3 0  mi n utes  
A U C i nf 
area u n d er t he pl as ma c o nce ntrati o n vers us ti me c ur ve fr o m a d mi nistrati o n t o 
i nfi nit y p ost-d ose  
C ma x  
ma xi m u m plas ma c o nce ntrati o n  
T ½  
plas ma c o nce ntrati o n half -life 
T ma x  
ti me t o reac h ma xi m u m plas ma c o nce ntrati o n  
 
 
 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 7 0 /7 8  
C O N FI D E N T I A L  
1 0. 5  A p pe n di x 6 : List of N a m es a n d A d dresses 
S p o ns or  
Zeala n d P har ma A/ S  
C V R N o. D K 2 0 0 4 5 0 7 8  
S y d mar k e n 1 1 
D K -2 8 6 0 S ø b or g, De n mar k  
C o ntract Researc h Or ga nizati o n ( C R O)  
S y nteract De utsc hla n d G m b H  
Stefa n -Ge or ge -Ri n g 6  
8 1 9 2 9  M u nic h, Ger ma n y  
Safet y C R O  
P har ma Le x A/ S  
A ger n Allé 2 4,  
D K -2 9 7 0 H ørs h ol m, De n mar k  
Trial m o nit or  
S y nteract De utsc hla n d G m b H  
Stefa n -Ge or ge -Ri n g 6  
8 1 9 2 9  M u nic h, Ger ma n y  
Bi ostatisticia n  
 
 
S y nteract De utsc hla n d G m b H  
Stefa n -Ge or ge -Ri n g 6  
8 1 9 2 9  M u nic h, Ger ma n y  
S p o ns or re prese ntati ve  
 
 
 
  
Zeala n d P har ma A/ S  
C V R N o. D K 2 0 0 4 5 0 7 8  
S y d mar ke n 1 1  
D K -2 8 6 0 S ø b or g, De n mar k  
S p o ns or’s me dical e x pert  
 M D 
 
 
Zeala n d P har ma A/ S  
C V R N o. D K 2 0 0 4 5 0 7 8  
S y d mar ke n 1 1  
D K -2 8 6 0 S ø b or g, De n mar k  
S p o ns or re prese ntati ve f or p har mac o vi gila nce  
 
P har ma Le x A/ S  
A ger n Allé 2 4,  
D K -2 9 7 0 H ørs h ol m, De n mar k  
Cli nical la b orat or y  
P P D Ce ntral La b U S  
Hi g hla n d Hei g hts, K Y  
2 Tesse neer R oa d  
Hi g hla n d Hei g hts,  
Ke nt uc k y 4 1 0 7 6 - 9 1 6 7  
U nite d States  
+ 1 8 5 9 7 8 1 8 8 7 7  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 7 1 /7 8  
C O N FI D E N T I A L  
C o nti n u o u s gl uc ose m o nit ori n g ( G C M) ve n d or  
I Q VI A 
I Q VI A Lt d. 
B N P Pari bas, L o n d o n Bra nc h  
1 0 Hare w o o d A ve n ue  
L o n d o n  
N W 1 6 A A  
  
 
  
 
A nal ytical la b orat or y  
( Z P 4 2 0 7 P K, Z P 4 2 0 7 a nti-dr u g a nti b o dies)  
 
 
 
 
 
 
( Z P 4 2 0 7 cell-base d ne utralizi n g a nti b o dies)  
 
Y or k Bi oa nal ytical S ol uti o ns ( Y B S)  
Ce dar H o use  
N ort h mi nster B usi ness Par k  
N ort hfiel d La ne  
Y or k, Y O 2 6 6 Q R  
U nite d Ki n g d o m  
 
Bi o A gil yti x La bs  
2 3 0 0 E n glert Dri ve  
D ur ha m, N C 2 7 7 1 3  
U S A  
 
 
 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 7 2 /7 8  
C O N FI D E N T I A L  
1 0. 6  A p pe n di x 7: S u m m ar y of C h a n ges fr o m V e rsi o n 5  t o Versi o n 6  
S U M M A R Y O F C H A N G E S F O R A P R O T O C O L A M E N D M E N T  
P R O T O C O L A M E N D M E N T 6  
Pr ot oc ol Title:  
A P hase 3, si n gle -a d mi nistrati o n, o pe n -la bel trial t o 
assess t he efficac y, safet y, p har mac o ki netics, a n d 
p har mac o d y n a mics of dasi gl uca g o n w he n 
a d mi nistere d as a resc u e t hera p y f or se vere 
h y p o gl yce mia i n pe diatri c patie n ts bel o w 6 years of 
a ge wit h T y pe 1 Dia b etes ( T 1 D)  
Pr ot oc ol N u m ber:  
Z P 4 2 0 7 -2 1 0 5 2  
Cli nic al P h ase:  
P hase  3  
Pr ot oc ol V ersi o n a n d D ate:  
Pr ot oc ol Versi o n 5 . 0, 0 1 N o v 2 0 2 3  
Ori gi n al Pr ot oc ol  
Versi o n 1, 1 0  Mar  2 0 2 2  
D ate A me n de d  
Versi o n 2. 0, 1 4 Oct 2 0 2 2  
Versi o n 3. 0, 1 2  Dec  2 0 2 2  
 
Versi o n 4. 0, 0 9  Mar 2 0 2 3  
Versi o n 5. 0, 0 1 N o v 2 0 2 3  
Versi o n 6. 0, 0 9 J ul 2 0 2 4  
U S I n vesti g ati o n al Ne w 
Dr u g N u m ber:  
1 2 7 8 6 6  
S p o ns or:  
Zeala n d P har m a A/ S  
C V R N o. D K 2 0 0 4 5 0 7 8  
S y d mar ke n 1 1  
D K -2 8 6 0 S ø b or g  
De n mar k  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 7 3 /7 8  
C O N FI D E N T I A L  
R A TI O N A L E F O R A M E N D M E N T  
T he rati o nale f or t his a m e n d me nt is t o all o w f or m ore fle xi bilit y i n recr uiti n g c hil dre n eli gi ble 
f or 0. 3 m g d ose b y re m o vi n g u p per li mit f or b o d y wei g ht of 1 5 k g.  
C ha n ges t o t he pr ot oc ol  are s u m marize d b el o w.  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 7 4 /7 8  
C O N FI D E N T I A L  
Secti o n n u m ber a n d 
he a di n g(s)  
Ol d te xt  
Ne w te xt  
J ustific ati o n f or c h a n ge  
S p o ns or Si g nat or y  
1 0. 5 A p pe n di x  6  
 
U p date d  
U p date d wit h a ne w si g nat or y  
d ue t o c o m pa n y tea m c h a n ges.  
1. 1 S y n o psis  
R ati o n ale:  
Dasi gl uca g o n is i n dicate d f or treat me nt of 
se v ere h y p o gl yce mia i n pe diatric a n d a d ult 
patie nts wit h dia betes a ge d 6 years a n d 
a b o ve. As t his c o n diti o n als o affects 
c hil dre n bel o w 6 years of a ge a n d t here is a 
t hera p e utic nee d f or t he m t o get access t o 
safe a n d efficaci o us e mer ge nc y treat me nt, 
t he prese nt trial ai ms t o assess t he efficac y 
a n d safet y of a si n gle s u bc uta ne o us ( S C) 
i njecti o n of dasi gl uca g o n i n c hil dre n bel o w 
6 years of a ge wit h T 1 D. A t otal of 8 
c hil dre n will be i ncl u de d; 4 c hil dre n 
recei vi n g a d ose of 0. 3 m g a n d 4 c hil dre n 
recei vi n g a d ose of 0. 6 m g. Of t he 4 c hil dre n 
recei vi n g 0. 3 m g, 2 c hil dre n s h o ul d 
prefera bl y be bel o w 2 years at scree ni n g. 
T he c hil dre n a ge d 2 years or a b o ve 
recei vi n g 0. 3 m g s h o ul d wei g h bel o w 1 5 k g 
at scree ni n g a n d s h o ul d prefera bl y be bel o w 
4 years at scree ni n g. F or c hil dre n recei vi n g 
the 0. 6 m g d ose, all m ust be a b o ve 2 years at 
scree ni n g. T he trial p o p ulati o n will i ncl u de 
c hil dre n treate d wit h S C i ns uli n i nf usi o n via 
i ns uli n p u m p or m ulti ple dail y i njecti o ns i n 
or der t o i ncl u de c hil dre n bel o w 1 year of 
a g e. O verall, t he eli gi bilit y cri teria all o w f or 
e nr oll me nt of a trial p o p ulati o n rese m bli n g  
t he tar get p o p ulati o n of c hil dre n bel o w 6 
years of a ge wit h T 1 D.  
R ati o n ale:  
Dasi gl uca g o n is i n dicate d f or treat me nt of 
se vere h y p o gl yce mia i n pe diatric a n d a d ult 
patie nts wit h dia betes a ge d 6 year s a n d a b o ve. 
As t his c o n diti o n als o affects c hil dre n bel o w 6 
years of a ge a n d t here is a t hera p e utic nee d 
f or t he m t o get access t o safe a n d efficaci o us 
e mer ge nc y treat me nt, t he prese nt trial ai ms t o 
assess t he efficac y a n d safet y of a si n gle 
s u bc uta ne o us ( S C) i njecti o n of dasi gl uca g o n 
i n c hil dre n bel o w 6 years of a ge wit h T 1 D. A 
t otal of 8 c hil dre n will be i ncl u de d; 4 c hil dre n 
recei vi n g a d ose of 0. 3 m g a n d 4 c hil dre n 
recei vi n g a d ose of 0. 6 m g. Of t he 4 c hil dre n 
recei vi n g 0. 3 m g, 2 c hil dre n s h o ul d preferabl y 
be bel o w 2 years at scree ni n g. T he  re m ai ni n g 
2  c hil dre n a ge d 2 years or a b o ve recei vi n g 0. 3 
m g s h o ul d wei g h bel o w 1 5 k g at scree ni n g 
a n d  s h o ul d prefera bl y be bel o w 4 years at 
scree ni n g. F or c hil dre n recei vi n g t he 0. 6 m g 
d ose, all m ust be a b o ve 2 years at scree ni n g. 
T he trial p o p ulati o n will i ncl u de c hil dre n 
treate d wit h S C i ns uli n i nf usi o n via i ns uli n 
p u m p or m ulti ple dail y i njecti o ns i n or der t o  
i ncl u de c hil dre n bel o w 1 year of a g e. O verall, 
t he eli gi bilit y criteria all o w f or e nr oll me nt of 
a trial p o p ulati o n rese m bli n g t he tar get 
p o p ulati o n of c hil dre n bel o w 6 years of a g e 
wit h T 1 D.  
T h e r ati o n al e f or t his 
a m e n d m e nt is t o all o w f or m or e 
fl e xi bility i n r e cr uiti n g c hil dr e n 
eli gi bl e f or 0. 3 m g d os e b y 
r e m o vi n g u p p er li mit f or b o d y 
w ei g ht of 1 5 k g.  
 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 7 5 /7 8  
C O N FI D E N T I A L  
1. 1 S y n o psis  
4. 1 O verall Desi g n  
  
O ver all Desi g n:  
T his trial will use a si n gle -a d mi nistrati o n, 
o pe n -la bel trial desi g n t o assess t he a bilit y 
of a si n gle S C i njecti o n of dasi gl uca g o n t o 
i ncrease plas ma gl uc ose i n pe diatric 
c hil dre n  wit h T 1 D wit h h y p o gl yce mia. A 
t otal of 8 c hil dre n will be i ncl u de d; 4 
c hil dre n recei vi n g a d ose of 0. 3 m g a n d 
4  c hil dre n recei vi n g a d ose of 0. 6 m g. Of t he 
4 c hil dre n recei vi n g 0. 3 m g, 2 c hil dre n 
s h o ul d prefera bl y be bel o w 2 years at 
scree ni n g. T he c hil dre n a ge d 2 years or 
a b o ve rece i vi n g 0. 3 m g s h o ul d wei g h bel o w 
1 5 k g at scree ni n g a n d s h o ul d prefera bl y be 
bel o w 4 years at scree ni n g.  F or c hil dre n 
recei vi n g t he 0. 6 m g d ose, all m ust be a b o ve 
2 years at scree ni n g. Bef ore a n eli gi ble c hil d 
is d ose d, t he d ose le vel ( 0. 6 m g or 0. 3  m g) 
m us t b e c o nfir me d b y t he s p o ns or. Eac h 
c hil d will be d ose d after t he safet y 
assess me nt of t he prece di n g c hil d has bee n 
c o m plete d a n d assesse d b y t he Trial Safet y 
Gr o u p.  
O verall Desi g n:  
T his trial will use a si n gle -a d mi nistrati o n, 
o pe n -la bel trial desi g n t o assess t he a bilit y of 
a si n gle S C i njecti o n of dasi gl uca g o n t o 
i ncrease plas ma gl uc ose i n pe diatric c hil dre n  
wit h T 1 D wit h h y p o gl yce mia. A t otal of 
8  c hil dre n will be i ncl u de d; 4 c hil dre n 
recei vi n g a d ose of 0. 3 m g a n d 4 c hil dre n 
recei vi n g a d ose of 0. 6 m g. Of t he 4 c hil dre n 
recei vi n g 0. 3 m g, 2 c hil dre n s h o ul d prefera bl y 
be bel o w 2 years at scree ni n g. T he  re m ai ni n g 
2  c hil dre n a ge d 2 years or a b o ve recei vi n g 0. 3 
m g s h o ul d wei g h bel o w 1 5 k g at scree ni n g 
a n d s h o ul d prefera bl y be bel o w 4 years at 
scree ni n g. F or c hil dre n recei vi n g t he 0. 6 m g 
d ose, all m ust be a b o ve 2 years at scree ni n g. 
Bef ore a n eli gi ble c hil d is d ose d, t he d ose 
le vel ( 0. 6 m g or 0. 3  m g) m ust be c o nfir me d 
b y t he s p o ns or. Eac h c hil d will b e d ose d after 
t he safet y assess me nt of t he prece di n g c hil d 
ha s bee n c o m plete d a n d assesse d b y t he Trial 
Safet y Gr o u p.  
1. 1 S y n o psis  
N u m ber of Patie nts:  
At least 8 c hil dre n bel o w 6 years (at t he 
scree ni n g visit) wit h T 1 D will be d ose d i n 
t he trial. T w o of t hese c hil dre n s h o ul d 
prefera bl y be bel o w 2 years of a ge at t he 
scree ni n g visit a n d s uccessf ull y c o m plete 
Visit 2. F urt her m ore, 2 c hil dre n s h o ul d 
wei g h bel o w 1 5 k g at scree ni n g a n d s h o ul d 
prefera bl y be bel o w 4 years.  
N u m ber of Patie nts:  
At least 8 c hil dre n bel o w 6 years (at t he 
scree ni n g visit) wit h T 1 D will be d ose d i n t he 
trial. T w o of t hese c hil dre n s h o ul d prefera bl y 
be bel o w 2 years of a ge at t he scree ni n g visit 
a n d s uccessf ull y c o m plete Visit 2. 
F urt her m ore, t he re mai ni n g 2 c hil dre n s h o ul d 
wei g h bel o w 1 5 k g at scree ni n g a n d s h o ul d 
prefera bl y be bel o w 4 years.  
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 7 6 /7 8  
C O N FI D E N T I A L  
1. 1 S y n o psis  
I nter v e nti o n Gr o u ps a n d D u r ati o n: 
All 8 c hil dre n will be treate d wit h 
dasi gl uca g o n via a si n gle S C i njecti o n i nt o 
t he b utt oc ks at t he d osi n g visit ( Visit 2).  
F o ur  c hil dre n i n t he a ge ra n ge ≥ 2 a n d < 6 
years:  
• will recei ve a si n gle S C i njecti o n of 0. 6 
m g/ 0. 6 m L of dasi gl uca g o n b y a prefille d 
s yri n ge. 
F o ur c hil dre n 2 of w hic h s h o ul d prefera bl y 
be bel o w 2 years, a n d t he c hil dre n a ge d ≥ 2 
years a n d prefera bl y < 4 years, wit h a b o d y  
wei g h bel o w 1 5 k g  
• will recei ve a si n gle S C i njecti o n of 0. 3 
m g/ 0. 3 m L dasi gl uca g o n b y a s yri n ge  
I nter ve nti o n Gr o u ps a n d D u r ati o n:  
All 8 c hil dre n will be treate d wit h 
dasi gl uca g o n via a si n gle S C i njecti o n i nt o t he 
b utt oc ks at t he d osi n g visit ( Visit 2).  
F o ur c hil dre n i n t he a ge ra n ge ≥ 2 a n d < 6 
years:  
• will recei ve a si n gle S C i njecti o n of 0. 6 
m g/ 0. 6 m L of dasi gl uca g o n b y a prefille d 
s yri n ge. 
F o ur c hil dre n 2 of w hic h s h o ul d prefera bl y be 
bel o w 2 years, a n d t he c hil dre n a g e d ≥ 2 years 
a n d prefera bl y < 4 years , wit h a b o d y wei g h 
bel o w 1 5 k g  
• will recei ve a si n gle S C i njecti o n of 0. 3 
m g/ 0. 3 m L dasi gl uca g o n b y a s yri n ge  
J ustificati o n f or D ose 
P har ma k o kite netics  
4. 3. 1  
 
C hil dre n wei g hi n g < 1 5 k g a n d prefera bl y < 
4 years: j ustificati o n f or 0. 3 m g d ose  
T he fi nal P o p P K m o del ( St u d y 1 9 -0 7 7) 
s h o we d a mea n C ma x a n d A U C t hat was 1. 4 
a n d 1. 1  ti mes hi g her i n 0- t o 1 -year -ol ds f or 
a d ose of 0. 3 m g c o m pare d t o t he e x p os ure 
i n a d ults wit h 0. 6 m g, res pecti vel y. T he rati o 
was 0. 9 a n d 0. 7 f or C ma x a n d A U C i n 3 - t o 
4 -year -ol ds f or a d ose of 0. 3 m g c o m pare d 
t o t he e x p os ure i n a d ults wit h 0. 6 m g, 
res pecti vel y. 
T he alter nati v e m o del i n dicate d t hese val ues 
f or C ma x a n d A U C t o be 4. 0 a n d 3. 1 ti mes 
hi g her i n 0 - t o 1-year -ol ds a n d 2. 0 a n d 1. 7 
ti mes hi g her i n 3- t o 4-year -ol ds c o m pare d 
t o a d ults. T he s pa n of P K pre dicti o ns base d 
C hil dre n wei g hi n g < 1 5 k g a n d prefera bl y < 4 
years: j ustificati o n f or 0. 3 m g d ose  
T he fi nal P o p P K m o del ( St u d y 1 9 -0 7 7) 
s h o we d a mea n C ma x a n d A U C t hat was 1. 4 
a n d 1. 1  ti mes hi g her i n 0- t o 1-year -ol ds f or a 
d ose of 0. 3 m g c o m pare d t o t he e x p os ure i n 
a d ults wit h 0. 6  m g, res pecti vel y. T he rati o 
was 0. 9 a n d 0. 7 f or C ma x a n d A U C i n 3 - t o 4-
year -ol ds f or a d ose of 0. 3 m g c o m pare d t o 
t he e x p os ure i n a d ults wit h 0. 6 m g, 
res pecti vel y. 
T he alter nati ve m o del i n dicate d t hese val ues 
f or Cma x a n d A U C t o be 4. 0 a n d 3. 1 ti mes 
hi g her i n 0 - t o 1-year -ol ds a n d 2. 0 a n d 1. 7 
ti mes hi g her i n 3- t o 4-year -ol ds c o m pare d t o 
a d ults. T he s pa n of P K pre dicti o ns base d o n 
T he ra ti o nale f or t his 
a me n d me nt is t o all o w f or m ore 
fle xi bilit y i n recr uiti n g c hil dre n 
eli gi ble f or 0. 3 m g d ose b y 
re m o vi n g u p per li mit f or b o d y 
wei g ht of 1 5 k g.  
 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 7 7 /7 8  
C O N FI D E N T I A L  
 
N otes: Stri ket hr o u g h  i n dicates delete d te xt, a n d b ol d  i dicates ne w te xt. 
 
 
 
o n t he fi nal a n d alter nati ve P K m o dels ca n 
be see n as  a p ossi ble realistic ra n ge.  
 
t he fi nal a n d alter nati ve P K m o dels ca n be 
see n as a p ossi ble realistic ra n ge. 
 
J ustificati o n f or D ose 
P har mac o ki netics  
4. 3. 2  
C hil dre n wei g hi n g < 1 5 k g a n d prefera bl y < 
4 years: j ustificati o n f or 0. 3 m g d ose  
Si nce t he pre dicte d C ma x fr o m b ot h P K 
m o dels ( 0. 3 m g d ose: fi nal m o del: 9 2 6 t o 
3, 6 6 0  p m ol/ L i n c hil dre n a ge d 0 t o 1  years 
a n d alter nati ve m o del: 2, 6 0 0 t o 
1 0, 5 0 0  p m ol/ L i n c hil dre n a ge d 0 t o 1  years) 
is s ubsta ntiall y l o wer (at least 2. 9 ti mes 
l o wer) t ha n t he o bser ve d c o nce ntrati o n 
ra n ge, t he use of 0. 3 m g dasi gl uca g o n is 
c o nsi dere d t o be safe i n c hil dre n wei g hi n g 
bel o w 1 5  k g ( prefera bl y bel o w 4 years) wit h 
re g ar ds t o t he ris k of Q T pr ol o n gati o n. 
 
C hil dre n w ei g hi n g < 1 5 k g a n d  prefera bl y < 4 
years: j ustificati o n f or 0. 3 m g d ose  
Si nce t he pre dicte d C ma x fr o m b ot h P K 
m o dels ( 0. 3 m g d ose: fi nal m o del: 9 2 6 t o 
3, 6 6 0  p m ol/ L i n c hil dre n a ge d 0 t o 1  years 
a n d alter nati ve m o del: 2, 6 0 0 t o 
1 0, 5 0 0  p m ol/ L i n c hil dre n a ge d  0 t o 1  years) 
is s u bsta ntiall y l o wer (at least 2. 9 ti mes 
l o wer) t ha n t he o bser ve d c o nce ntrati o n ra n ge, 
t he  use of 0. 3 m g dasi gl uca g o n is c o nsi dere d 
t o be safe i n c hil dre n wei g hi n g bel o w 1 5 k g 
( prefera bl y bel o w 4 years) wit h re g ar ds t o t he 
ris k of Q T pr ol o n gati o n. 
 
T he rati o nale f or t his 
a me n d me nt is t o all o w f or m ore 
fle xi bilit y i n recr uiti n g c hil dre n 
eli gi ble f or 0. 3 m g d ose b y 
re m o vi n g u p per li mit f or b o d y 
wei g ht of 1 5 k g.  
 
S U B- 1 7 2 9 8   1. 0

 
Zeala n d P har ma A/ S  
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2  
Versi o n 6 . 0, 1 2  J ul 2 0 2 4  
 
Pr ot oc ol Z P 4 2 0 7 -2 1 0 5 2 _ Fi nal  V 6 . 0 _1 2  J ul 2 0 2 4  
Pa ge 7 8 /7 8  
C O N FI D E N T I A L  
1 1  R E F E R E N C E S  
1.  Dasi gl uca g o n ( Z e gal o g u e) U S Prescri bi n g I nf or m ati o n. A vaila ble at: 
htt ps:// w w w.access data.f da. g o v/ dr u gsatf da _ d o cs/la bel/ 2 0 2 1/ 2 1 4 2 3 1s 0 0 0l bl. p df . 
2.  Sea q uist E R, A n ders o n J., C hil ds B, et al. H y p o gl yce mia a n d  dia betes: A re p ort of a 
w or k gr o u p of t he A merica n Dia betes Ass o ciati o n a n d t he E n d ocri n e S ociet y. Di a betes 
C are . 2 0 1 3; 3 6( 5): 1 3 8 4 -9 5.  
3.  Dasi gl uca g o n I n v esti gat or Br oc h ure, E diti o n 1 1 , 1 0  J u n 2 0 2 2 . Zeala n d P har ma A/ S. 
4.  Witjes  H , Di deric hse n P. M . P o p ulati o n P har mac o ki netic M o deli n g of Dasi gl uca g o n i n 
S u bjects wit h T y pe I Dia betes Mellit us . 3 1 Ja n 2 0 2 0.  Z eala n d P har m a  A/ S  re p ort 1 9 -0 7 7 . 
5.  H o wie, S R. Bl o o d sa m ple v ol u mes i n c hil d healt h researc h: r e vie w of safe li mits. B ull eti n 
of t he W orl d He alt h Or g a n iz ati o n. 2 0 1 1;  8 9( 1) :4 6 – 5 3. d oi: 1 0. 2 4 7 1/ B L T. 1 0. 0 8 0 0 1 0  
6.  Bi oa nal ytical Met h o d Vali dati o n, G ui da nce f or I n d ustr y pre pare d b y t he Office of 
Cli nical P har mac ol o g y i n t he Ce nter f or Dr u g E val uati o n a n d Researc h a n d t he Ce nter 
f or Veteri nar y Me dici ne at t he F o o d a n d Dr u g A d mi nistrati o n. Ma y 2 0 1 8. 
7.  Electr o nic S o urce Data i n Cli nical I n vesti gati o ns, G ui da nce f or I n d ustr y pre pare d b y t h e 
Ce nter f or Dr u g E val uati o n a n d Researc h, Ce nter f or Bi ol o gics E val uati o n a n d Researc h, 
a n d Ce nter f or De vic es a n d Ra di ol o gical Healt h at t he F o o d a n d Dr u g A d mi nistrati o n. 
Se pte m ber  2 0 1 3.  
S U B- 1 7 2 9 8   1. 0

Si g nat ure Pa ge f or S U B- 1 7 2 9 8 v 1. 0
Si g nat ure Pa ge f or S U B- 1 7 2 9 8 v 1. 0
A p pr o val Tas k
Ver dict: A p pr o ve d
S M E A p pr o val
1 1-J ul- 2 0 2 4 1 2: 4 8: 2 1 G M T + 0 0 0 0
A p pr o val Tas k
Ver dict: A p pr o ve d
S M E A p pr o val
1 1-J ul- 2 0 2 4 1 2: 4 8: 3 4 G M T + 0 0 0 0
A p pr o val Tas k
Ver dict: A p pr o ve d
S M E A p pr o val
1 1-J ul- 2 0 2 4 1 6: 0 4: 0 9 G M T + 0 0 0 0
S U B- 1 7 2 9 8   1. 0