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Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

Overview

Status
Completed
Phase
Phase 3
Enrollment
42 participants (actual)
Sponsor
Zealand Pharma · Industry
Design
Randomized · Quadruple masking
Countries
3 countries

United States, Germany, Slovenia

Start
28 Sept 2018
Primary completion
28 Jun 2019
Completion
28 Jun 2019
First posted
12 Sept 2018
Last update posted
30 Jun 2021
Conditions
Hypoglycemia

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201820192020
  1. Ph 3

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

    NCT03667053

    28 Sept 2018 to 28 Jun 2019

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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

Interventions

  • dasiglucagonDrug
  • placeboDrug
  • GlucaGen HypoKitDrug

Arms3

  • Experimental

    dasiglucagon

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

  • Placebo comparator

    placebo

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

  • Active comparator

    GlucaGen®

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

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Time to Plasma Glucose Recovery

    Time frame · 0-45 minutes after dosing

    Registry description

    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. Time to plasma glucose recovery was summarized for each treatment group using Kaplan Meier (KM) estimates together with the 95% confidence interval. Note that the upper confidence limit for the placebo median was not estimable, but is set to 45 minutes (censored value) here.

Secondary outcomes(15)
  1. Plasma Glucose Recovery

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

    Registry description

    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. Plasma glucose recovery was defined as the first increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L) from baseline without administration of rescue intravenous glucose.

  2. Plasma Glucose Changes From Baseline

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

    Registry description

    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

    Registry description

    Plasma glucose response as area under the effect curve above baseline from time 0 to 30 minutes (AUE0-30min). Plasma glucose was determined at pre-dose and at 4, 6, 8, 10, 12, 15, 17, 20, 30, and 45 minutes (and at 60 minutes if the patient weighed ≥21 kg) after dosing.

  4. Administration of Rescue IV Glucose Infusion After IMP Injection

    Time frame · 0-45 minutes

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMedian· 0-45 minutes after dosing

Time to Plasma Glucose Recovery

GroupValue (minutes)
Dasiglucagon 0.6 mg10.00
Placebo30.00
GlucaGen® 1.0 mg10.00
Secondary and other outcome results(7)
Secondary outcomeCount of participants· 0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection

Plasma Glucose Recovery

GroupValue (Participants)
Dasiglucagon 0.6 mg20
Placebo6
GlucaGen® 1.0 mg10
Secondary outcomeMean· 0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection

Plasma Glucose Changes From Baseline

GroupValue (mg/dL)Spread
Dasiglucagon 0.6 mg98.45919.6527
Placebo17.51015.6313
GlucaGen® 1.0 mg85.22512.5052
Secondary outcomeMean· 0-30 minutes

Pharmacodynamics - Area Under the Effect Curve (0-30 Minutes)

GroupValue (mmol*h/L)Spread
Dasiglucagon 0.6 mg22.836.126
Placebo1.814.641
GlucaGen® 1.0 mg19.663.410
Secondary outcomeCount of participants· 0-45 minutes

Administration of Rescue IV Glucose Infusion After IMP Injection

GroupValue (Participants)
Dasiglucagon 0.6 mg0
Placebo1
GlucaGen® 1.0 mg0
Secondary outcomeNumber· 0-45 minutes

Time to First IV Glucose Infusion After IMP Administration

GroupValue (minutes)
Dasiglucagon 0.6 mgnot posted
Placebo12
GlucaGen® 1.0 mgnot posted
Secondary outcomeGeometric mean· 0-30 minutes

Pharmacokinetics: AUC0-30 Min

GroupValue (h*pmol/L)Spread
Dasiglucagon 0.6 mg37678.1
GlucaGen® 1.0 mg37663.3
Secondary outcomeGeometric mean· 0-300 minutes

Pharmacokinetics: AUC0-300min

GroupValue (h*pmol/L)Spread
Dasiglucagon 0.6 mg181044.8
GlucaGen® 1.0 mg137072.7

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Age Group 6-11 Years - DasiglucagonPatients in the dasiglucagon group in the age group 6-11 years0 / 80 / 83 / 8
Age Group 6-11 Years - PlaceboPatients in the placebo group in the age group 6-11 years0 / 40 / 41 / 4
Age Group 6-11 Years - GlucaGenPatients in the GlucaGen group in the age group 6-11 years0 / 40 / 44 / 4
Age Group 12-17 Years - DasiglucagonPatients in the dasiglucagon group in the age group 12-17 years0 / 120 / 1212 / 12
Age Group 12-17 Years - PlaceboPatients in the placebo group in the age group 12-17 years0 / 70 / 76 / 7
Age Group 12-17 Years - GlucagenPatients in the GlucaGen group in the age group 12-17 years0 / 60 / 65 / 6
Dasiglucagon 0.6 mgFull population. Single fixed dose (subcutaneous injection) of dasiglucagon0 / 200 / 2015 / 20
PlaceboFull population. Single fixed dose (subcutaneous injection) of placebo0 / 110 / 117 / 11
GlucaGen® 1.0 mgFull population. Single fixed dose (subcutaneous injection) of GlucaGen® (0.5 mg if body weight \<25 kg)0 / 100 / 109 / 10

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 6 Years up to 17 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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 \- 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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