Clinical trial NCT03378635: A Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Type 1 Diabetes Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypoglycemia
Diabetes Mellitus, Type 1
Keywords: Dasiglucagon
Glucagon analog
Lead sponsor: Zealand Pharma
Sponsor class: INDUSTRY
First posted: 2017-12-20
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 (T1DM) with insulin-induced hypoglycemia. Additionally to compare the glycemic response observed after administration dasiglucagon with that of GlucaGen®.

Detailed description: This was a global, multicenter, randomized, parallel, and double-blind clinical trial confirming the efficacy and safety of dasiglucagon for insulin-induced hypoglycemia in patients with T1DM. The patients were randomized 2:1:1 to receive a single subcutaneous 0.6 mg dose of dasiglucagon, placebo, or a 1 mg dose of GlucaGen and followed for at least 28 days after receiving treatment.

Eligibility criteria: Inclusion Criteria:

* Female or male subjects with type 1 diabetes mellitus (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

Primary outcomes:
measure: Time to Plasma Glucose Recovery
timeFrame: 0-45 minutes after dosing
Secondary outcomes:
measure: Plasma Glucose Recovery
timeFrame: 0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection
measure: Plasma Glucose Changes From Baseline
timeFrame: 0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection
measure: Time to Target
timeFrame: 0-45 minutes after dosing
measure: Pharmacodynamics - Area Under the Effect Curve
timeFrame: 0-30 minutes after dosing
measure: Pharmacokinetics - Area Under the Plasma Concentration Curve
timeFrame: 0-90 minutes after dosing
measure: Pharmacokinetics - Area Under the Plasma Concentration Curve
timeFrame: 0-120 minutes after dosing
measure: Pharmacokinetics - Maximum Plasma Concentration
timeFrame: 0-120 minutes after dosing
measure: Pharmacokinetics - Time to Maximum Plasma Concentration
timeFrame: 0-120 minutes after dosing
measure: Immunogenicity - Occurence of Anti-drug Antibodies
timeFrame: 28 days
measure: Rescue Infusion of IV Glucose During the Hypoglycemic Clamp Procedure
timeFrame: 0-45 minutes after dosing
measure: Time to First Rescue Infusion of IV Glucose
timeFrame: 0-45 minutes after dosing
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: ProSciento
state: California
city: Graz
country: Austria
facility: Clinical Research Center, Medizinische Universität Graz
city: Toronto
country: Canada
facility: LMC Diabetes & Manna Research
city: Mainz
country: Germany
facility: Profil
city: Neuss
country: Germany
facility: Profil
Study officials:
affiliation: Zealand Pharma
name: Christina Sylvest, MSc Pharm
role: STUDY_DIRECTOR
References:
citation: Pieber TR, Aronson R, Hovelmann U, Willard J, Plum-Morschel L, Knudsen KM, Bandak B, Tehranchi R. Dasiglucagon-A Next-Generation Glucagon Analog for Rapid and Effective Treatment of Severe Hypoglycemia: Results of Phase 3 Randomized Double-Blind Clinical Trial. Diabetes Care. 2021 Jun 1;44(6):1361-1367. doi: 10.2337/dc20-2995.