A Trial to Evaluate the Immunogenicity of Dasiglucagon and GlucaGen in Patients With Type 1 Diabetes Mellitus

• Sponsor: Zealand Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03216226
• Collaborator: SynteractHCR (Industry)
• Enrollment: 112
• Locations: 7
• Arms: 2
• Actual Duration (Months): 7.6
• Patients Per Site: 16
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

The trial's objective is to evaluate the immunogenicity of repeated single doses of dasiglucagon* and GlucaGen following subcutaneous (SC) administration in patients with type 1 diabetes mellitus (T1DM) and further to evaluate the safety and tolerability of dasiglucagon and GlucaGen.

*dasiglucagon is the proposed International Nonproprietary Name (pINN) for ZP4207

Condition or Disease	Intervention/Treatment	Phase
Hypoglycemia; Diabetes Mellitus, Type 1	Drug: dasiglucagon; Drug: GlucaGen	Phase 3

Detailed Description

Patients with T1DM were randomly assigned in a 1:1 ratio to receive 3 SC injections of either dasiglucagon (0.6 mg) or GlucaGen (1 mg), with 1 week between doses. Patients were followed for 15 weeks from the day of the first dose to assess the immune response. Patients with previous exogenic glucagon exposure were not excluded from the trial, but the information on previous glucagon administration was recorded to enable subgroup analyses. It was expected that 112 patients in total would be randomly assigned to treatment groups and treated. A total of 90 patients were expected to complete the trial (45 in each treatment arm). To qualify as completed, the patient had to be dosed according to the procedure described in the protocol and to have blood drawn for the antidrug antibody analyses as scheduled.

Study Design

• Study Type: Interventional
• Actual Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blind, Parallel Group Safety Trial to Evaluate the Immunogenicity of Dasiglucagon and GlucaGen® Administered Subcutaneously in Patients With Type 1 Diabetes Mellitus (T1DM)
• Actual Study Start Date: Jun 28, 2017
• Actual Primary Completion Date: Feb 13, 2018
• Actual Study Completion Date: Feb 13, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: dasiglucagon (ZP4207) Repeated single fixed doses (s.c.injection) of dasiglucagon	Drug: dasiglucagon; Glucagon Analog; Other Names: ZP4207
Experimental: GlucaGen Repeated single fixed doses (s.c.injection) of GlucaGen	Drug: GlucaGen; Native Glucagon; Other Names: GlucaGen HypoKit

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With ADA [104 days after the first dose]

   Percentage of the combined results of treatment-induced ADA-positive patients and treatment-boosted ADA-positive patients out of the total number of evaluable patients. ADA = antidrug antibodies.

Secondary Outcome Measures

1. Percentage of Patients With Treatment-induced ADA [104 days after the first dose]

   Percentage of the total number of evaluable patients that were ADA negative at baseline and ADA positive after drug administration out of the total number of evaluable patients. ADA = antidrug antibodies

2. Percentage of Patients With Treatment-boosted ADA [104 days after the first dose]

   Percentage of baseline ADA-positive patients with significant increases (≥5-fold) in ADA titre after drug administration out of the total number of evaluable patients. ADA = antidrug antibodies

3. Characterization of ADA Response - Neutralizing Activity [104 days after the first dose]

   Percentage of ADA positive patients with ADA neutralizing activity. ADA = antidrug antibodies.

4. Characterization of ADA Response - Titer of Neutralizing Activity [104 days after the first dose]

   Titre of neutralizing activity of ADA positive patients. ADA = antidrug antibodies.

5. Characterization of ADA Response - Cross-reactivity [104 days after the first dose]

   Percentage of ADA positive patients with cross-reactivity towards endogenous glucagon. ADA = antidrug antibodies.

6. Characterization of ADA Response - Timing [104 days after the first dose]

   The timing of detected ADA response. ADA = antidrug antibodies.

7. Characterization of ADA Response - Duration [104 days after the first dose]

   The Duration of detected ADA response. ADA = antidrug antibodies.

8. Pharmacokinetics - Area Under the Plasma Concentration Curve [0-30 minutes]

   Area under the plasma concentration curve (AUC) 0-30 minutes at visit 2 and 4 (days 0 and 14). Plasma PK concentrations were measured before dosing and at 5, 10 and 30 minutes after dosing.

9. Pharmacokinetics - Area Under the Plasma Concentration Curve [0-90 minutes]

   Area under the plasma concentration curve (AUC) 0-90 minutes at visit 2 and 4 (days 0 and 14). Plasma PK concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.

10. Pharmacokinetics - Maximum Plasma Concentration [90 minutes]

    Maximum plasma concentration (Cmax) at visit 2 and 4 (days 0 and 14). Plasma PK concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.

11. Pharmacokinetics - Time to Maximum Plasma Concentration [90 minutes]

    Time to maximum plasma concentration (Tmax) at visit 2 and 4 (days 0 and 14). Plasma PK concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.

12. Pharmacodynamics - Area Under the Effect Curve [0-30 minutes]

    Plasma glucose profiles, area under the effect curve (AUE) 0-30 minutes at visit 2 and 4 (days 0 and 14). Plasma glucose concentrations were measured before dosing and at 5, 10 and 30 minutes after dosing.

13. Pharmacodynamics - Area Under the Effect Curve [0-90 minutes]

    Plasma glucose profiles, area under the effect curve (AUE) 0-90 minutes at visit 2 and 4 (days 0 and 14). Plasma glucose concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.

14. Pharmacodynamics - Change From Baseline Plasma Glucose [90 minutes]

    Change from baseline plasma glucose to maximum plasma glucose (CEmax) at visit 2 and 4 (days 0 and 14). Plasma glucose concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.

15. Pharmacodynamics - Time to Maximum Plasma Glucose Concentration [90 minutes]

    Time to maximum plasma glucose concentration (Tmax) at visit 2 and 4 (days 0 and 14). Plasma glucose concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.

16. Pharmacodynamics - An Increase in the Plasma Glucose Concentration of ≥20 mg/dL Within 30 Minutes After Treatment [30 minutes]

    An increase in the plasma glucose concentration of ≥20 mg/dL within 30 minutes after treatment at visit 2 and visit 4. Plasma glucose concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Informed consent obtained before any trial-related activities (trial-related activities are any procedure that would not have been performed during normal management of the patient)

• Availability for the entire trial period

• Age between 18 and 70 years, both inclusive

• Male or female patients with T1DM for at least 1 year. Diagnostic criteria as defined by the American Diabetes Association

• Hemoglobin A1c (HbA1c) <10%

• Stable anti-diabetic treatment for at least 1 month (e.g. within 10% insulin dose adjustment)

Exclusion Criteria:

• Previous administration of dasiglucagon (previously referred to as ZP4207)

• Known or suspected allergy to trial medication(s) or related products

• History of anaphylaxis or symptoms of severe systemic allergy (such as angioedema)

• Previous participation (randomization) in this trial

• Females who are pregnant according to a positive pregnancy test, actively attempting to get pregnant, or are lactating

• Patients on a closed loop artificial pancreas

• Receipt of any investigational drug within 3 months prior to screening

• Active malignancy within the last 5 years

• Congestive heart failure, New York Heart Association class II-IV

• Inadequately treated blood pressure as defined as systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥90 mmHg at screening

• Current bleeding disorder, including use of anticoagulant treatment

• Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin-secreting pancreas tumor)

• Known or suspected HIV infection

• Use of a systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this trial

• Use of systemic corticosteroids, anti-inflammatory biological agents, kinase inhibitors or other immune modulating agents within the last 3 months prior to screening

• Donation of blood or plasma in the past month, or in excess of 500 mL within 12 weeks prior to screening

• A positive result in the alcohol and/or urine drug screen at the screening visit. Significant history of alcoholism or drug abuse as judged by the investigator or consuming more than 24 g alcohol per day for men, or more than 12 g alcohol per day for women.

• Surgery or trauma with significant blood loss within the last 2 months prior to screening

• Use of prescription or non-prescription medications known to cause QT prolongation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Compass Research	Orlando	Florida	United States	32806
2	Advanced Clinical Research	Meridian	Idaho	United States	83642
3	CRC - Clinical Research Center, Medizinische Universität Graz	Graz		Austria
4	LMC Manna Research	Barrie		Canada
5	LMC Calgary	Calgary		Canada
6	LMC Diabetes & Manna Research	Toronto		Canada
7	Diabeteszentrum Hamburg West, Gemeinschaftspraxis für Innere Medizin	Hamburg		Germany

Sponsors and Collaborators

• Zealand Pharma
• SynteractHCR

Investigators

• Study Director: Christina Sylvest, MSc Pharm, Zealand Pharma A/S

Study Documents (Full-Text)

• Study Protocol - Aug 21, 2017
• Statistical Analysis Plan - Mar 19, 2018

More Information

Publications

None provided.

• Responsible Party: Zealand Pharma
• ClinicalTrials.gov Identifier: NCT03216226
• Other Study ID Numbers: ZP4207-16136
• First Posted: Jul 13, 2017
• Last Update Posted: May 4, 2021
• Last Verified: Apr 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Zealand Pharma: Glucagon; Dasiglucagon
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia; Glucagon

Study Results

Participant Flow

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Period Title: Overall Study
STARTED	57	55
Randomized and Treated	57	54
COMPLETED	52	50
NOT COMPLETED	5	5

Baseline Characteristics

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen	Total
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon	Total of all reporting groups
Overall Participants	57	54	111
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	55 96.5%	52 96.3%	107 96.4%
>=65 years	2 3.5%	2 3.7%	4 3.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.3 (12.21)	38.8 (13.65)	42.1 (13.29)
Sex: Female, Male (Count of Participants)
Female	16 28.1%	22 40.7%	38 34.2%
Male	41 71.9%	32 59.3%	73 65.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.8%	0 0%	1 0.9%
Asian	4 7%	2 3.7%	6 5.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 3.5%	0 0%	2 1.8%
White	50 87.7%	52 96.3%	102 91.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Canada	28 49.1%	26 48.1%	54 48.6%
Austria	15 26.3%	15 27.8%	30 27%
United States	5 8.8%	5 9.3%	10 9%
Germany	9 15.8%	8 14.8%	17 15.3%
Body weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	82.9 (18.44)	82.7 (16.25)	82.8 (17.33)
Body mass index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.2 (4.88)	27.4 (4.70)	27.3 (4.77)

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With ADA
Description	Percentage of the combined results of treatment-induced ADA-positive patients and treatment-boosted ADA-positive patients out of the total number of evaluable patients. ADA = antidrug antibodies.
Time Frame	104 days after the first dose

Outcome Measure Data

Analysis Population Description

Full analysis set of all patients in the safety analysis set (those randomized who received at least 1 dose of trial product) with at least 1 measurement of ADA titres at baseline

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	56	54
Patients with ADA	0 0%	0 0%
Patients without ADA	56 98.2%	54 100%

2. Secondary Outcome

Title	Percentage of Patients With Treatment-induced ADA
Description	Percentage of the total number of evaluable patients that were ADA negative at baseline and ADA positive after drug administration out of the total number of evaluable patients. ADA = antidrug antibodies
Time Frame	104 days after the first dose

Outcome Measure Data

Analysis Population Description

Full analysis set of all patients in the safety analysis set (those randomized who received at least 1 dose of trial product) with at least 1 measurement of ADA titres at baseline

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	56	54
Patients with ADA	0 0%	0 0%
Patients without ADA	56 98.2%	54 100%

3. Secondary Outcome

Title	Percentage of Patients With Treatment-boosted ADA
Description	Percentage of baseline ADA-positive patients with significant increases (≥5-fold) in ADA titre after drug administration out of the total number of evaluable patients. ADA = antidrug antibodies
Time Frame	104 days after the first dose

Outcome Measure Data

Analysis Population Description

Full analysis set of all patients in the safety analysis set (those randomized who received at least 1 dose of trial product) with at least 1 measurement of ADA titres at baseline

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	56	54
Patients with ADA	0 0%	0 0%
Patients without ADA	56 98.2%	54 100%

4. Secondary Outcome

Title	Characterization of ADA Response - Neutralizing Activity
Description	Percentage of ADA positive patients with ADA neutralizing activity. ADA = antidrug antibodies.
Time Frame	104 days after the first dose

Outcome Measure Data

Analysis Population Description

No ADAs were recorded in this trial, therefore it was not possible to characterize the ADA response.

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	0	0

5. Secondary Outcome

Title	Characterization of ADA Response - Titer of Neutralizing Activity
Description	Titre of neutralizing activity of ADA positive patients. ADA = antidrug antibodies.
Time Frame	104 days after the first dose

Outcome Measure Data

Analysis Population Description

No ADAs were recorded in this trial, therefore it was not possible to characterize the ADA response in terms of titre of neutralizing activity.

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	0	0

6. Secondary Outcome

Title	Characterization of ADA Response - Cross-reactivity
Description	Percentage of ADA positive patients with cross-reactivity towards endogenous glucagon. ADA = antidrug antibodies.
Time Frame	104 days after the first dose

Outcome Measure Data

Analysis Population Description

No ADAs were recorded in this trial, therefore it was not possible to characterize the ADA response in terms of cross-reactivity towards endogenous glucagon.

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	0	0

7. Secondary Outcome

Title	Characterization of ADA Response - Timing
Description	The timing of detected ADA response. ADA = antidrug antibodies.
Time Frame	104 days after the first dose

Outcome Measure Data

Analysis Population Description

No ADAs were recorded in this trial, therefore it was not possible to characterize the ADA response in terms of timing.

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	0	0

8. Secondary Outcome

Title	Characterization of ADA Response - Duration
Description	The Duration of detected ADA response. ADA = antidrug antibodies.
Time Frame	104 days after the first dose

Outcome Measure Data

Analysis Population Description

No ADAs were recorded in this trial, therefore it was not possible to characterize the ADA response in terms of duration.

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	0	0

9. Secondary Outcome

Title	Pharmacokinetics - Area Under the Plasma Concentration Curve
Description	Area under the plasma concentration curve (AUC) 0-30 minutes at visit 2 and 4 (days 0 and 14). Plasma PK concentrations were measured before dosing and at 5, 10 and 30 minutes after dosing.
Time Frame	0-30 minutes

Outcome Measure Data

Analysis Population Description

PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic.

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	57	54
Day 0	425 (220)	548 (226)
Day 14	499 (371)	546 (181)

10. Secondary Outcome

Title	Pharmacokinetics - Area Under the Plasma Concentration Curve
Description	Area under the plasma concentration curve (AUC) 0-90 minutes at visit 2 and 4 (days 0 and 14). Plasma PK concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.
Time Frame	0-90 minutes

Outcome Measure Data

Analysis Population Description

PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic.

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	57	54
Day 0	1560 (615)	1290 (434)
Day 14	1640 (611)	1290 (379)

11. Secondary Outcome

Title	Pharmacokinetics - Maximum Plasma Concentration
Description	Maximum plasma concentration (Cmax) at visit 2 and 4 (days 0 and 14). Plasma PK concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.
Time Frame	90 minutes

Outcome Measure Data

Analysis Population Description

PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic.

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	57	54
Day 0	1390 (609)	1490 (537)
Day 14	1820 (2460)	1430 (498)

12. Secondary Outcome

Title	Pharmacokinetics - Time to Maximum Plasma Concentration
Description	Time to maximum plasma concentration (Tmax) at visit 2 and 4 (days 0 and 14). Plasma PK concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.
Time Frame	90 minutes

Outcome Measure Data

Analysis Population Description

PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic.

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	57	54
Day 0	0.5	0.483
Day 14	0.5	0.5

13. Secondary Outcome

Title	Pharmacodynamics - Area Under the Effect Curve
Description	Plasma glucose profiles, area under the effect curve (AUE) 0-30 minutes at visit 2 and 4 (days 0 and 14). Plasma glucose concentrations were measured before dosing and at 5, 10 and 30 minutes after dosing.
Time Frame	0-30 minutes

Outcome Measure Data

Analysis Population Description

PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic.

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	57	54
Day 0	0.799 (0.449)	0.886 (0.504)
Day 14	0.869 (0.375)	0.895 (0.511)

14. Secondary Outcome

Title	Pharmacodynamics - Area Under the Effect Curve
Description	Plasma glucose profiles, area under the effect curve (AUE) 0-90 minutes at visit 2 and 4 (days 0 and 14). Plasma glucose concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.
Time Frame	0-90 minutes

Outcome Measure Data

Analysis Population Description

PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic.

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	57	54
Day 0	5.9 (2.42)	5.86 (3.14)
Day 14	6.47 (2.28)	6.04 (2.63)

15. Secondary Outcome

Title	Pharmacodynamics - Change From Baseline Plasma Glucose
Description	Change from baseline plasma glucose to maximum plasma glucose (CEmax) at visit 2 and 4 (days 0 and 14). Plasma glucose concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.
Time Frame	90 minutes

Outcome Measure Data

Analysis Population Description

PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic.

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	57	54
Day 0	6.25 (2.5)	6 (3.01)
Day 14	6.88 (2.43)	6.21 (2.65)

16. Secondary Outcome

Title	Pharmacodynamics - Time to Maximum Plasma Glucose Concentration
Description	Time to maximum plasma glucose concentration (Tmax) at visit 2 and 4 (days 0 and 14). Plasma glucose concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.
Time Frame	90 minutes

Outcome Measure Data

Analysis Population Description

PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic.

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	57	54
Day 0	1.5	1.5
Day 14	1.5	1.5

17. Secondary Outcome

Title	Pharmacodynamics - An Increase in the Plasma Glucose Concentration of ≥20 mg/dL Within 30 Minutes After Treatment
Description	An increase in the plasma glucose concentration of ≥20 mg/dL within 30 minutes after treatment at visit 2 and visit 4. Plasma glucose concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.
Time Frame	30 minutes

Outcome Measure Data

Analysis Population Description

PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic.

Arm/Group Title	Dasiglucagon (ZP4207)	GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog	3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
Measure Participants	57	54
Yes	54 94.7%	51 94.4%
No	3 5.3%	3 5.6%
Yes	51 89.5%	47 87%
No	1 1.8%	2 3.7%

Adverse Events

Time Frame	104 days
Adverse Event Reporting Description	Adverse events were recorded at each trial visit by the investigator or other designated trial personnel.
Arm/Group Title	Dasiglucagon (ZP4207)		GlucaGen
Arm/Group Description	3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog		3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon
All Cause Mortality
	Dasiglucagon (ZP4207)		GlucaGen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57 (0%)		0/54 (0%)
Serious Adverse Events
	Dasiglucagon (ZP4207)		GlucaGen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/57 (1.8%)		0/54 (0%)
Metabolism and nutrition disorders
Hypoglycemia	1/57 (1.8%)	1	0/54 (0%)	0
Other (Not Including Serious) Adverse Events
	Dasiglucagon (ZP4207)		GlucaGen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/57 (73.7%)		43/54 (79.6%)
Blood and lymphatic system disorders
Leukocytosis	2/57 (3.5%)	2	4/54 (7.4%)	5
Eye disorders
Retinopathy	0/57 (0%)	0	2/54 (3.7%)	2
Gastrointestinal disorders
Nausea	26/57 (45.6%)	43	23/54 (42.6%)	33
Vomiting	12/57 (21.1%)	18	8/54 (14.8%)	9
Diarrhea	4/57 (7%)	4	2/54 (3.7%)	2
General disorders
Fatigue	1/57 (1.8%)	1	1/54 (1.9%)	1
Injection site erythema	0/57 (0%)	0	2/54 (3.7%)	3
Infections and infestations
Viral upper respiratory tract infection	6/57 (10.5%)	7	8/54 (14.8%)	9
Upper respiratory tract infection	2/57 (3.5%)	2	4/54 (7.4%)	4
Metabolism and nutrition disorders
Hypoglycemia	27/57 (47.4%)	580	29/54 (53.7%)	447
Hyperglycemia	3/57 (5.3%)	3	2/54 (3.7%)	8
Musculoskeletal and connective tissue disorders
Back pain	0/57 (0%)	0	2/54 (3.7%)	2
Nervous system disorders
Headache	8/57 (14%)	14	3/54 (5.6%)	4
Dizziness	2/57 (3.5%)	2	3/54 (5.6%)	3
Skin and subcutaneous tissue disorders
Erythema	0/57 (0%)	0	3/54 (5.6%)	4
Vascular disorders
Hypotension	2/57 (3.5%)	2	2/54 (3.7%)	3
Hypertension	1/57 (1.8%)	1	2/54 (3.7%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.