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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 : June 30, 2021
Sponsor:
Information provided by (Responsible Party):
Zealand Pharma

Tracking Information
First Submitted Date  ICMJE September 7, 2018
First Posted Date  ICMJE September 12, 2018
Results First Submitted Date  ICMJE April 13, 2021
Results First Posted Date  ICMJE May 10, 2021
Last Update Posted Date June 30, 2021
Actual Study Start Date  ICMJE September 28, 2018
Actual Primary Completion Date June 28, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2021)
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. 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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 7, 2018)
Time to plasma glucose recovery [ Time Frame: 0-45 minutes after dosing ]
Plasma glucose recovery is 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 IV glucose.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2021)
  • Plasma Glucose Recovery [ Time Frame: 0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection ]
    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.
  • Plasma Glucose Changes From Baseline [ Time Frame: 0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection ]
    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
  • 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). 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2018)
  • 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 IV glucose
  • 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 IV glucose
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in T1DM Children
Official Title  ICMJE 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
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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Hypoglycemia
Intervention  ICMJE
  • Drug: dasiglucagon
    glucagon analog
    Other Name: ZP4207
  • Drug: placebo
    placebo for dasiglucagon
    Other Name: placebo for dasiglucagon
  • Drug: GlucaGen HypoKit
    native glucagon
Study Arms  ICMJE
  • Experimental: dasiglucagon
    Single fixed dose (s.c.injection) of dasiglucagon
    Intervention: Drug: dasiglucagon
  • Placebo Comparator: placebo
    Single fixed dose (s.c.injection) of placebo
    Intervention: Drug: placebo
  • Active Comparator: GlucaGen®
    Single fixed dose (s.c.injection) of GlucaGen®
    Intervention: Drug: GlucaGen HypoKit
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 3, 2019)
42
Original Estimated Enrollment  ICMJE
 (submitted: September 7, 2018)
40
Actual Study Completion Date  ICMJE June 28, 2019
Actual Primary Completion Date June 28, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

-

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Slovenia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03667053
Other Study ID Numbers  ICMJE ZP4207-17086
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Zealand Pharma
Study Sponsor  ICMJE Zealand Pharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Christina M Sylvest, MSc Pharm Zealand Pharma A/S
PRS Account Zealand Pharma
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP