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

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03688711
• Other study ID #: ZP4207-17145
• Status: Completed
• Phase: Phase 3
• Start date: November 1, 2018
• Est. completion date: March 11, 2019

Study information

• Verified date: April 2021
• Source: Zealand Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: March 11, 2019
• Est. primary completion date: March 11, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hypoglycemia

Intervention

Drug:
• Dasiglucagon
Glucagon analogue
• Placebo
Placebo for dasiglucagon

Locations

Country	Name	City	State
United States	ProSciento, Inc.	Chula Vista	California
United States	AMCR Institute	Escondido	California
United States	Rainier Clinical Research, Inc.	Renton	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Zealand Pharma

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Plasma Glucose Recovery.	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.	0-45 minutes after dosing
Secondary	Plasma Glucose Recovery After Trial Drug Injection	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.	0-30 minutes after dosing
Secondary	Plasma Glucose Changes From Baseline	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).	0-30 minutes after dosing
Secondary	Time to Target Plasma Glucose Concentration	Time to first plasma glucose concentration =70 mg/dL (3.9 mmol/L) without administration of rescue intravenous glucose	0-45 minutes after dosing
Secondary	Pharmacodynamics - Area Under the Effect Curve	Plasma glucose response as area under the effect curve (AUE) above baseline from time zero to 30 minutes, AUE0-30min.	0-30 minutes after dosing
Secondary	Pharmacokinetics - Area Under the Plasma Concentration Curve	Area under the drug concentration curve (AUC) from time zero to 90 minutes, AUC0-90min	0-90 minutes after dosing
Secondary	Pharmacokinetics - Area Under the Plasma Concentration Curve	Area under the drug concentration curve (AUC) from time zero to 120 minutes, AUC0-120min	0-120 minutes after dosing
Secondary	Pharmacokinetics - Maximum Plasma Concentration	Maximum plasma dasiglucagon concentration (Cmax)	0-120 minutes after dosing
Secondary	Pharmacokinetics - Time to Maximum Plasma Concentration	Time to maximum plasma dasiglucagon concentration (tmax)	0-120 minutes after dosing
Secondary	Immunogenicity - Occurrence of Anti-drug Antibodies	Occurrence of antibodies against dasiglucagon. Presented as percentage of patients with antibodies.	58 days
Secondary	Rescue Infusions of IV Glucose After Trial Drug Administration	Presented as number of patients with rescue infusions of IV glucose after trial drug administration. This was a safety outcome measure. IV = intravenous	0-45 minutes after dosing
Secondary	Time to First Rescue Infusion of IV Glucose After Trial Drug Administration	Safety outcome measure: time to first rescue infusion of IV glucose after trial drug administration. IV = intravenous	0-45 minutes after dosing