- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03667053
Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in T1DM Children
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Hannover, Germany, 30173
- Auf der Bult - Diabetes Center for Children
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Ljubljana, Slovenia, 1000
- University Medical Center Ljubljana, Children's Hospital, Department for Endocrinology, Diabetes and Metabolism
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California
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Escondido, California, United States, 92025
- Amcr Institute, Inc
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Connecticut
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New Haven, Connecticut, United States, 06520
- Yale University School Of Medicine
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Indiana
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Indianapolis, Indiana, United States, 46202
- Indiana University, Department of Pediatrics
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
- Female or male patients with T1DM for at least 1 year, diagnostic criteria as defined by the American Diabetes Association; and receiving daily insulin
- At least 6.0 years of age (inclusive) and less than 18.0 years
- Body weight ≥20 kg
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
- 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
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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Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: dasiglucagon
Single fixed dose (s.c.injection) of dasiglucagon
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glucagon analog
Other Names:
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PLACEBO_COMPARATOR: placebo
Single fixed dose (s.c.injection) of placebo
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placebo for dasiglucagon
Other Names:
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ACTIVE_COMPARATOR: GlucaGen®
Single fixed dose (s.c.injection) of GlucaGen®
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native glucagon
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Time to Plasma Glucose Recovery
Time Frame: 0-45 minutes after dosing
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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. |
0-45 minutes after dosing
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Plasma Glucose Recovery
Time Frame: 0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection
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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.
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0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection
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Plasma Glucose Changes From Baseline
Time Frame: 0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection
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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
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0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection
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Pharmacodynamics - Area Under the Effect Curve (0-30 Minutes)
Time Frame: 0-30 minutes
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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.
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0-30 minutes
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Administration of Rescue IV Glucose Infusion After IMP Injection
Time Frame: 0-45 minutes
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Number of patients receiving IV rescue glucose administration for hypoglycemia after administration of IMP.
IV = intravenous.
IMP = investigational medicinal product.
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0-45 minutes
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Time to First IV Glucose Infusion After IMP Administration
Time Frame: 0-45 minutes
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Time to first IV rescue glucose administration for hypoglycemia after administration of IMP.
IV = intravenous.
IMP = investigational medicinal product.
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0-45 minutes
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Pharmacokinetics: AUC0-30 Min
Time Frame: 0-30 minutes
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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.
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0-30 minutes
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Pharmacokinetics: AUC0-300min
Time Frame: 0-300 minutes
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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.
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0-300 minutes
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Pharmacokinetics: AUC0-inf
Time Frame: 0-300 minutes
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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.
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0-300 minutes
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Pharmacokinetics: Cmax
Time Frame: 0-300 minutes
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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.
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0-300 minutes
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Pharmacokinetics: Tmax
Time Frame: 0-300 minutes
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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.
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0-300 minutes
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Pharmacokinetics: λz
Time Frame: 0-300 minutes
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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.
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0-300 minutes
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Pharmacokinetics: t½
Time Frame: 0-300 minutes
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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.
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0-300 minutes
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Pharmacokinetics: CL/f
Time Frame: 0-300 minutes
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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.
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0-300 minutes
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Pharmacokinetics: Vz/f
Time Frame: 0-300 minutes
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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.
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0-300 minutes
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Pharmacokinetics: MRT
Time Frame: 0-300 minutes
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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.
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0-300 minutes
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ZP4207-17086
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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