Trial to Confirm the Clinical Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in Subjects With T1DM

Phase 3

Completed

• Conditions: Hypoglycemia; Diabetes Mellitus, Type 1
• Interventions: Drug: Placebo; Drug: Dasiglucagon

• Registration Number: NCT03688711
• Lead Sponsor: Zealand Pharma

Brief Summary

A randomized, double-blind, parallel-group trial to confirm the clinical efficacy and safety of dasiglucagon in the rescue treatment of hypoglycemia in subjects with type 1 diabetes mellitus (T1DM) compared to placebo

Detailed Description

Subjects were randomized in a ratio of 3:1 to receive a single subcutaneous dose of dasiglucagon (0.6 mg) or matching placebo. Randomization also determined whether the subject was to be injected in the buttock or deltoid. During the dosing visit (Visit 2), hypoglycemia was induced by a fast-acting insulin glulisine (Apidra®) infusion, and trial drug was administered when the subject's plasma glucose level was 45-60 mg/dL (2.5-3.3 mmol/L). During the insulin-induced hypoglycemia, pharmacokinetic and pharmacodynamic samples were drawn, and plasma glucose levels were monitored closely at site for safety reasons. A rescue glucose infusion could be administered to ameliorate persistent hypoglycemia. Subjects were followed for at least 28 days after dosing to perform an adequate immunogenicity evaluation of treatment.

Study Timeline

• Study First Submitted: 2018-09-25
• Study First Submitted QC: 2018-09-27
• Study First Posted: 2018-09-28
• Study Start: 2018-11-01
• Primary Completion: 2019-03-11
• Study Completion: 2019-03-11
• Disposition First Submitted: 2020-03-10
• Results First Submitted: 2021-03-26
• Status Verified: 2021-04
• Results First Submitted QC: 2021-04-28
• Disposition First Submitted QC: 2021-04-28
• Last Update Submitted: 2021-04-28
• Results First Posted: 2021-05-19
• Disposition First Posted: 2021-05-19
• Last Update Posted: 2021-05-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

• Female or male subjects with T1DM for at least 1 year; diagnostic criteria as defined by the American Diabetes Association (3).
• 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%.
• Aged between 18 and 75 years, both inclusive.

Exclusion Criteria

• Previous participation in a clinical trial within the dasiglucagon in the rescue treatment of hypoglycemia program.
• Known or suspected allergy to trial drug(s) or related products.
• History of anaphylaxis or symptoms of severe systemic allergy (such as angioedema).
• Previous participation in this trial. Participation being defined by signing the informed consent document.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	single fixed dose (subcutaneous injection) of placebo
Dasiglucagon	Dasiglucagon	single fixed dose (subcutaneous injection) of dasiglucagon

Primary Outcome Measures

Name	Time	Method
Time to Plasma Glucose Recovery.	0-45 minutes after dosing	Plasma glucose recovery was 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 intravenous (IV) glucose. Patients who received rescue IV glucose before 45 minutes and patients not recovering within 45 minutes after dosing were censored at 45 minutes.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics - Time to Maximum Plasma Concentration	0-120 minutes after dosing	Time to maximum plasma dasiglucagon concentration (tmax)
Time to First Rescue Infusion of IV Glucose After Trial Drug Administration	0-45 minutes after dosing	Safety outcome measure: time to first rescue infusion of IV glucose after trial drug administration. IV = intravenous
Plasma Glucose Recovery After Trial Drug Injection	0-30 minutes after dosing	Plasma glucose recovery (patient has achieved increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L)) within 30 minutes, within 20 minutes, within 15 minutes, and within 10 minutes after trial drug injection without administration of rescue intravenous (IV) glucose.
Immunogenicity - Occurrence of Anti-drug Antibodies	58 days	Occurrence of antibodies against dasiglucagon. Presented as percentage of patients with antibodies.
Plasma Glucose Changes From Baseline	0-30 minutes after dosing	Plasma glucose changes from baseline at 30 minutes, at 20 minutes, at 15 minutes, and at 10 minutes after trial drug injection or at the time of rescue (patient level).
Time to Target Plasma Glucose Concentration	0-45 minutes after dosing	Time to first plasma glucose concentration ≥70 mg/dL (3.9 mmol/L) without administration of rescue intravenous glucose
Rescue Infusions of IV Glucose After Trial Drug Administration	0-45 minutes after dosing	Presented as number of patients with rescue infusions of IV glucose after trial drug administration. This was a safety outcome measure. IV = intravenous
Pharmacodynamics - Area Under the Effect Curve	0-30 minutes after dosing	Plasma glucose response as area under the effect curve (AUE) above baseline from time zero to 30 minutes, AUE0-30min.
Pharmacokinetics - Area Under the Plasma Concentration Curve	0-120 minutes after dosing	Area under the drug concentration curve (AUC) from time zero to 120 minutes, AUC0-120min
Pharmacokinetics - Maximum Plasma Concentration	0-120 minutes after dosing	Maximum plasma dasiglucagon concentration (Cmax)

Trial Locations

Locations (3)

Rainier Clinical Research, Inc.; 🇺🇸 Renton, Washington, United States

AMCR Institute; 🇺🇸 Escondido, California, United States

ProSciento, Inc.; 🇺🇸 Chula Vista, California, United States