Clinical trial NCT05378672
Conditions: Hypoglycemia Type 1 Diabetes
Keywords: Hypoglycemia Low Blood Sugar Type 1 Diabetes Diabetes T1D
Sponsor: Zealand Pharma
Start date: 2023-05-09; Completion date: 2024-12-03
Enrollment: 8 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This research study will investigate whether dasiglucagon as a rescue therapy for participants under 6 years of age works and is safe to use. In addition, the study will investigate how dasiglucagon works in the body (pharmacokinetics and pharmacodynamics).

Participants will receive 1 single dose as an injection under the skin (subcutaneous, s.c.) into the buttocks.

Participants will have 3 visits with the study team. For each participant, the study will last up to 84 days.

Detailed description:
This trial will use a single-administration, open-label trial design to assess the ability of a single SC injection of dasiglucagon to increase plasma glucose in pediatric children with T1D with hypoglycemia. A total of 8 children will be included; 4 children receiving a dose of 0.3 mg and 4 children receiving a dose of 0.6 mg. Of the 4 children receiving 0.3 mg, 2 children should preferably be below 2 years at screening. The 2 additional children receiving 0.3 mg should weigh below 15 kg at screening and should preferably be below 4 years at screening. For children receiving the 0.6 mg dose, all must be above 2 years at screening. Before an eligible child is dosed, the dose level (0.6 mg or 0.3 mg) must be confirmed by the sponsor. Each child will be dosed after the safety assessment of the preceding child has been completed and assessed by the Trial Safety Group.

The trial will include the following visits:

* A screening visit (Visit 1) in the period from Day - 50 to Day - 29 (pre-treatment visit)
* A dosing visit (Visit 2), Day 1 (day of single dosing with investigational medicinal product \[IMP\])
* A Safety follow-up visit (Visit 3) at Day 29 +5 days (the end-of-trial visit).

The primary endpoint of the trial is plasma glucose change from baseline at 30 minutes after IMP injection or at the time of rescue by intravenous glucose. Pharmacodynamics (PD) i.e., plasma glucose will be assessed at baseline and 15 and 30 minutes after dosing, while the glucose levels will be monitored by continuous glucose monitoring and by a plasma glucose analyzer during the dosing visit (Visit 2). Pharmacokinetics (PK) will be assessed throughout a 300-minute period at the dosing visit (Visit 2). Safety will be assessed prior to dosing and throughout a 300-minute period after dosing and again at the follow-up visit.

Arms: arm 1: Participants will receive a single dose of 0.6 mg dasiglucagon. arm 2: Participants will receive a single dose of 0.3 mg dasiglucagon.
Interventions: intervention 1: Dasiglucagon
Intervention descriptions: intervention 1: Dasiglucagon, 0.6 mg/0.6 mL or 0.3 mg/0.3 mL will be administered as an under the skin (subcutaneous, s.c.) injection by a prefilled syringe, into the buttocks.

Protocol documents:
Prot_000.pdf: 
 
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

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