A Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Type 1 Diabetes Subjects

• ClinicalTrials.gov Identifier: NCT03378635
• Recruitment Status: Completed
• First Posted: December 20, 2017
• Last Update Posted: June 17, 2020
• Sponsor: Zealand Pharma
• Information provided by (Responsible Party): Zealand Pharma

Study Description

Brief Summary:

The objective of the trial is to demonstrate superiority of dasiglucagon compared to placebo following a single subcutaneous dose administered to subjects with type 1 diabetes mellitus with insulin-induced hypoglycemia. Additionaly to compare the glycemic response observed after administration dasiglucagon with that of GlucaGen®.

Condition or disease	Intervention/treatment	Phase
Hypoglycemia; Diabetes Mellitus, Type 1	Drug: Dasiglucagon; Drug: GlucaGen; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 170 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 Trial to Confirm the Clinical Efficacy and Safety of Dasiglucagon in Rescue Treatment of Hypoglycemia in Subjects With Type 1 Diabetes Mellitus Compared to Placebo and With Reference to GlucaGen
• Actual Study Start Date: December 7, 2017
• Actual Primary Completion Date: April 27, 2018
• Actual Study Completion Date: May 25, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dasiglucagon; Single fixed dose (s.c.injection) of dasiglucagon	Drug: Dasiglucagon; Glucagon analog; Other Name: ZP4207
Placebo Comparator: Placebo; Single fixed dose (s.c.injection) of placebo	Drug: Placebo; Placebo for dasiglucagon; Other Name: Placebo for dasiglucagon
Active Comparator: GlucaGen®; Single fixed dose (s.c.injection) of GlucaGen®	Drug: GlucaGen; Native glucagon; Other Name: GlucaGen HypoKit

Outcome Measures

Primary Outcome Measures :

1. Time to plasma glucose recovery [ Time Frame: 0-45 minutes after dosing ]
   Plasma glucose recovery is defined as first increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L) from baseline during the hypoglycemic clamp procedure without administration of rescue IV glucose.

Secondary Outcome Measures :

1. Plasma glucose recovery [ Time Frame: 0-30 minutes after dosing ]
   Plasma glucose recovery within 30 minutes, within 20 minutes, within 15 minutes, and within 10 minutes after study drug injection without administration of rescue IV glucose
2. Plasma glucose changes drom baseline [ Time Frame: 0-30 minutes after dosing ]
   Plasma glucose recovery within 30 minutes, within 20 minutes, within 15 minutes, and within 10 minutes after study drug injection without administration of rescue IV glucose
3. Time to target [ Time Frame: 0-45 minutes after dosing ]
   Time to first plasma glucose concentration ≥70 mg/dL (3.9 mmol/L) without administration of rescue IV glucose
4. Pharmacodynamics - Area under the effect curve [ Time Frame: 0-30 minutes after dosing ]
   Plasma glucose response as area under the curve (AUC) above baseline from time zero to 30 minutes, AUC0-30min.
5. Pharmacokinetics - Area under the plasma concentration curve [ Time Frame: 0-90 minutes after dosing ]
   Area under the drug concentration curve from time zero to 90 minutes, AUC0-90min
6. Pharmacokinetics - Maximum plasma concentration [ Time Frame: 0-120 minutes after dosing ]
   Maximum plasma drug concentration (Cmax)
7. Pharmacokinetics - Time to maximum plasma concentration [ Time Frame: 0-120 minutes after dosing ]
   Time to maximum plasma drug concentration (tmax)
8. Safety - Adverse events [ Time Frame: 28 days ]
   The incidence, type and severity of adverse events (AEs)
9. Safety - Biochemistry laboratory parameters [ Time Frame: 28 days ]
   Changes from baseline in biochemistry laboratory parameters
10. Safety - Hematology laboratory parameters [ Time Frame: 28 days ]
    Changes from baseline in hematology laboratory parameters
11. Safety - Blood pressure [ Time Frame: 28 days ]
    Changes from baseline in blood pressure (mmHg)
12. Safety - Pulse [ Time Frame: 28 days ]
    Changes from baseline in pulse (beats pr. min)
13. Safety - Physical Examination [ Time Frame: 28 days ]
    Clinically meaningful changes from baseline of the following body systems: head, ears, eyes, nose, throat, including the thyroid gland; heart, lung, chest; abdomen; skin and mucosae; musculoskeletal system; nervous system; lymph node
14. Safety - Electrocardiogram [ Time Frame: 28 days ]
    Clinically meaningful changes from baseline in electrocardiogram (ECG)
15. Safety - Injection site reactions [ Time Frame: 28 days ]
    The incidence, type and severity of injection site reactions
16. Safety - Glucose for rescue [ Time Frame: 0-45 minutes after dosing ]
    Administration of rescue infusion of IV glucose during the hypoglycemic clamp procedure
17. Immunogenicity - Occurence of anti-drug antibodies [ Time Frame: 28 days ]
    Occurence of antibodies against dasiglucagon/GlucaGen

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Female or male subjects with T1DM for at least 1 year, diagnostic criteria as defined by the American Diabetes Association
• Treated with insulin for T1DM for at least 1 year and with stable insulin treatment (defined as no more than a 10-unit daily variation in total daily insulin dose) 30 days prior to screening
• Hemoglobin A1c <10%

Exclusion Criteria:

• Previously treated with dasiglucagon (previously referred to as ZP4207)
• Known or suspected allergy to trial product(s) or related products
• Females who are pregnant according to a positive pregnancy test, are actively attempting to get pregnant, or are lactating.
• History of hypoglycemic events associated with seizures in the last year prior to screening
• History of severe hypoglycemia in the last month prior to screening
• Active malignancy within the last 5 years
• Current bleeding disorder, including anti-coagulant treatment
• Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin secreting pancreas tumor)
• Use of a daily systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this trial
• Clinically significant abnormal ECG at screening as judged by the investigator
• Donation of blood or plasma in the past month, or in excess of 500 mL within 12 weeks prior to screening
• Surgery or trauma with significant blood loss within the last 2 months 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

Contacts and Locations

Locations

United States, California

ProSciento

Chula Vista, California, United States, 91911

Austria

Clinical Research Center, Medizinische Universität Graz

Graz, Austria

Canada

LMC Diabetes & Manna Research

Toronto, Canada

Germany

Profil

Mainz, Germany

Profil

Neuss, Germany

Sponsors and Collaborators

Zealand Pharma

Investigators

• Study Director: Benedikte Bandak, MS; Zealand Pharma

More Information

• Responsible Party: Zealand Pharma
• ClinicalTrials.gov Identifier: NCT03378635
• Other Study ID Numbers: ZP4207-16137
• First Posted: December 20, 2017
• Last Update Posted: June 17, 2020
• Last Verified: June 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Zealand Pharma:

Glucagon

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Glucagon; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs