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

NCT03378635 | Completed Phase 3 Results FDA Drug

• 1 other identifier: ZP4207-16137
• Study Type: interventional
• Target: 170
• Locations: 4 countries
• Sites: 5

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®.

Conditions

Hypoglycemia; Diabetes Mellitus, Type 1

Keywords

Dasiglucagon; Glucagon analog

Outcome Measures

Primary Outcomes (1)

• Time to Plasma Glucose Recovery

  Plasma glucose recovery is defined as first increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L) from baseline without administration of rescue intravenous glucose. The outcome measure used a Kaplan-Meier estimate with 95% confidence interval. Treatment groups without censoring utilized a distribution free method to compute the confidence interval for median time.

  0-45 minutes after dosing

Secondary Outcomes (11)

• Plasma Glucose Recovery

  0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection

• Plasma Glucose Changes From Baseline

  0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection

• Time to Target

  0-45 minutes after dosing

• Pharmacodynamics - Area Under the Effect Curve

  0-30 minutes after dosing

• Pharmacokinetics - Area Under the Plasma Concentration Curve

  0-90 minutes after dosing

Study Arms (3)

Dasiglucagon

EXPERIMENTAL

Single fixed dose (s.c.injection) of dasiglucagon

Drug: Dasiglucagon

Placebo

PLACEBO COMPARATOR

Single fixed dose (s.c.injection) of placebo

Drug: Placebo

GlucaGen®

ACTIVE COMPARATOR

Single fixed dose (s.c.injection) of GlucaGen®

Drug: GlucaGen

Interventions

Dasiglucagon DRUG

Glucagon analog

Also known as: ZP4207

Dasiglucagon

GlucaGen DRUG

Native glucagon

Also known as: GlucaGen HypoKit

GlucaGen®

Placebo DRUG

Placebo for dasiglucagon

Also known as: Placebo for dasiglucagon

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Zealand Pharma: lead

Study Sites (5)

ProSciento

Chula Vista, California, 91911, United States

Location

Clinical Research Center, Medizinische Universität Graz

Graz, Austria

Location

LMC Diabetes & Manna Research

Toronto, Canada

Location

Profil

Mainz, Germany

Location

Profil

Neuss, Germany

Location

Related Publications (1)

• 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.

  PMID: 35239971 DERIVED

MeSH Terms

Conditions

Hypoglycemia; Diabetes Mellitus, Type 1

Interventions

dasiglucagon; Glucagon-Like Peptide 1

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Dr Kim Mark Knudsen
• Organization: Zealand Pharma A/S

KMKnudsen@zealandpharma.com

+4550603780

Study Officials

• Christina Sylvest, MSc Pharm

  Zealand Pharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2017
• First Posted: December 20, 2017
• Study Start: December 7, 2017
• Primary Completion: April 27, 2018
• Study Completion: May 25, 2018
• Last Updated: June 10, 2021
• Results First Posted: May 10, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (1); DE (2); AU (1)