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Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in T1DM Children

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ClinicalTrials.gov Identifier: NCT03667053
Recruitment Status : Completed
First Posted : September 12, 2018
Results First Posted : May 10, 2021
Last Update Posted : May 10, 2021
Sponsor:
Information provided by (Responsible Party):
Zealand Pharma

Brief Summary:
A phase 3, randomized, double-blind, placebo- and active-controlled, parallel-arm trial to assess the efficacy, safety, and pharmacokinetics of dasiglucagon relative to placebo and GlucaGen® when administered as a rescue therapy for severe hypoglycemia in children with type 1 diabetes mellitus (T1DM) treated with insulin

Condition or disease Intervention/treatment Phase
Hypoglycemia Drug: dasiglucagon Drug: placebo Drug: GlucaGen HypoKit Phase 3

Detailed Description:
At least 40 children ≥6 years and <18 years of age with T1DM were planned to be randomized into the trial (2:1:1 for dasiglucagon:placebo:GlucaGen) and stratified by age intervals: 6 years to <12 years, and 12 years to <18 years; and by injection site (abdomen or thigh). A minimum of 16 patients were enrolled into each age group, including a minimum of 8 patients in each age group in the dasiglucagon treatment arm. In Germany only, a staggered approach was applied, whereby a positive safety assessment needed to be available for at least 10 patients in the age group of 12 years to <18 years who had completed the dosing visit in the overall trial before younger patients (6 to 11 years of age) were allowed to be enrolled.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 3, Randomized, Double-blind, Placebo/Active-controlled, Parallel-arm Trial to Assess Efficacy, Safety, and Pharmacokinetics of Dasiglucagon Relative to Placebo/GlucaGen® as Rescue Therapy for Severe Hypoglycemia in Children With T1DM Treated With Insulin
Actual Study Start Date : September 28, 2018
Actual Primary Completion Date : June 28, 2019
Actual Study Completion Date : June 28, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypoglycemia
Drug Information available for: Glucagon

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 HypoKit
native glucagon




Primary Outcome Measures :
  1. Time to Plasma Glucose Recovery [ Time Frame: 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.

    Note that the upper confidence limit for the placebo median was not estimable, but is set to 45 minutes (censored value) here.



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 intravenous (IV) glucose

  2. Plasma Glucose Changes From Baseline [ Time Frame: 0-30 minutes after dosing ]
    Plasma glucose changes from baseline within 30 minutes, within 20 minutes, within 15 minutes, and within 10 minutes after trial product injection or at the time of rescue intravenous (IV) glucose

  3. Pharmacodynamics - Area Under the Effect Curve (0-30 Minutes) [ Time Frame: 0-30 minutes ]
    Plasma glucose response as area under the effect curve above baseline from time 0 to 30 minutes (AUE0-30min)

  4. Administration of Rescue IV Glucose Infusion After IMP Injection [ Time Frame: 0-45 minutes ]
    Number of patients receiving IV rescue glucose administration for hypoglycemia after administration of IMP. IV = intravenous. IMP = investigational medicinal product.

  5. Time to First IV Glucose Infusion After IMP Administration [ Time Frame: 0-45 minutes ]
    Time to first IV rescue glucose administration for hypoglycemia after administration of IMP. IV = intravenous. IMP = investigational medicinal product.

  6. Pharmacokinetics: AUC0-30 Min [ Time Frame: 0-30 minutes ]
    Area under the plasma dasiglucagon or GlucaGen concentration versus time curve from 0 to 30 minutes post-dose. Samples were collected before dosing and at 10, 20, 30, 40, 60, 90, 140, 220, and 300 minutes after dosing.

  7. Pharmacokinetics: AUC0-300min [ Time Frame: 0-300 minutes ]
    Area under the plasma dasiglucagon or GlucaGen concentration versus time curve from 0 to 300 minutes post-dose. Samples were collected before dosing and at 10, 20, 30, 40, 60, 90, 140, 220, and 300 minutes after dosing.

  8. Pharmacokinetics: AUC0-inf [ Time Frame: 0-300 minutes ]
    Area under the plasma dasiglucagon or GlucaGen concentration versus time curve from 0 to infinitely post-dose. Samples were collected before dosing and at 10, 20, 30, 40, 60, 90, 140, 220, and 300 minutes after dosing.

  9. Pharmacokinetics: Cmax [ Time Frame: 0-300 minutes ]
    Maximum of all valid plasma dasiglucagon or GlucaGen concentration measurements from 0 to 300 minutes post-dose. Samples were collected before dosing and at 10, 20, 30, 40, 60, 90, 140, 220, and 300 minutes after dosing.

  10. Pharmacokinetics: Tmax [ Time Frame: 0-300 minutes ]
    Time to maximum of plasma dasiglucagon or GlucaGen concentration measurements. Samples were collected before dosing and at 10, 20, 30, 40, 60, 90, 140, 220, and 300 minutes after dosing.

  11. Pharmacokinetics: λz [ Time Frame: 0-300 minutes ]
    Terminal elimination rate constant of plasma dasiglucagon or GlucaGen. Samples were collected before dosing and at 10, 20, 30, 40, 60, 90, 140, 220, and 300 minutes after dosing.

  12. Pharmacokinetics: t½ [ Time Frame: 0-300 minutes ]
    Terminal plasma elimination half-life of dasiglucagon or GlucaGen. Samples were collected before dosing and at 10, 20, 30, 40, 60, 90, 140, 220, and 300 minutes after dosing.

  13. Pharmacokinetics: CL/f [ Time Frame: 0-300 minutes ]
    Total body clearance of plasma dasiglucagon or GlucaGen. Samples were collected before dosing and at 10, 20, 30, 40, 60, 90, 140, 220, and 300 minutes after dosing.

  14. Pharmacokinetics: Vz/f [ Time Frame: 0-300 minutes ]
    Volume of distribution of plasma dasiglucagon or GlucaGen. Samples were collected before dosing and at 10, 20, 30, 40, 60, 90, 140, 220, and 300 minutes after dosing.

  15. Pharmacokinetics: MRT [ Time Frame: 0-300 minutes ]
    Mean residence time of plasma dasiglucagon or GlucaGen. Samples were collected before dosing and at 10, 20, 30, 40, 60, 90, 140, 220, and 300 minutes after dosing.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Following receipt of verbal and written information about the trial, patient, parent(s) or guardian(s) of the patient must provide signed informed consent before any trial-related activity is carried out
  2. Female or male patients with T1DM for at least 1 year, diagnostic criteria as defined by the American Diabetes Association; and receiving daily insulin
  3. At least 6.0 years of age (inclusive) and less than 18.0 years
  4. Body weight ≥20 kg
  5. Female patients must meet one of the following criteria:

    a. Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens throughout the entire duration of the trial from screening until last follow-up visit. An acceptable method of contraception includes at least one of the following: i. Abstinence from heterosexual intercourse ii. Systemic contraceptives (birth control pills, injectable/implant/ insertable hormonal birth control products, transdermal patch); if the participant is using systemic contraceptives, she must use an additional form of acceptable contraception (iii or iv, below) iii. Intrauterine device (with and without hormones) iv. Condom with spermicide or b. Participant is of non-childbearing potential due to pre-puberty status or a medical condition confirmed by the investigator

  6. Male patients must meet the following criteria: If sexually active, uses condom and partner practices contraception during the trial from screening and until last follow-up visit
  7. Willingness to adhere to the protocol requirements

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    Exclusion Criteria:

1. Females who are pregnant according to a positive urine pregnancy test, actively attempting to get pregnant, or are lactating 2. Known or suspected allergy to trial product(s) or related products 3. History of anaphylaxis or symptoms of severe systemic allergy (such as angioedema) 4. Previous randomization in this trial 5. History of an episode of severe hypoglycemia that required a third party assistance within a month prior to screening visit 6. History of hypoglycemic events associated with seizures or hypoglycemia unawareness in the last year prior to screening 7. History of epilepsy or seizure disorder 8. Receipt of any investigational drug within 3 months prior to screening 9. Active malignancy within the last 5 years 10. Congestive heart failure, New York Heart Association class II-IV 11. Current bleeding disorder, including anti-coagulant treatment 12. Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin secreting pancreas tumor) 13. Use of a daily systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this trial 14. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 × the upper limit of the normal range (ULN), bilirubin >1.5 × ULN, estimated glomerular filtration rate <30 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease study definition, or altered electrolyte values of clinical relevance for cardiac conduction, as judged by the investigator 15. Clinically significant abnormal electrocardiogram (ECG) at screening as judged by the investigator 16. Clinically significant illness within 4 weeks before screening, as judged by the investigator 17. Surgery or trauma with significant blood loss within the last 2 months prior to screening 18. Patients with mental incapacity or language barriers which preclude adequate understanding or cooperation, who are unwilling to participate in the trial, or who in the opinion of the investigator should not participate in the trial 19. Any condition interfering with trial participation or evaluation or that could be hazardous to the patient 20. The use of prescription or non-prescription medications known to cause QT prolongation

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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03667053


Locations
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United States, California
AMCR Institute, Inc
Escondido, California, United States, 92025
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06520
United States, Indiana
Indiana University, Department of Pediatrics
Indianapolis, Indiana, United States, 46202
Germany
Auf der Bult - Diabetes Center for Children
Hannover, Germany, 30173
Slovenia
University Medical Center Ljubljana, Children's Hospital, Department for Endocrinology, Diabetes and Metabolism
Ljubljana, Slovenia, 1000
Sponsors and Collaborators
Zealand Pharma
Investigators
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Study Director: Christina M Sylvest, MSc Pharm Zealand Pharma A/S
  Study Documents (Full-Text)

Documents provided by Zealand Pharma:
Study Protocol  [PDF] January 8, 2019
Statistical Analysis Plan  [PDF] August 16, 2019

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Responsible Party: Zealand Pharma
ClinicalTrials.gov Identifier: NCT03667053    
Other Study ID Numbers: ZP4207-17086
First Posted: September 12, 2018    Key Record Dates
Results First Posted: May 10, 2021
Last Update Posted: May 10, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Zealand Pharma:
Glucagon
Dasiglucagon
Additional relevant MeSH terms:
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Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Glucagon
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs