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
Overview
- Phase
- Phase 3
- Intervention
- GlucaGen HypoKit
- Conditions
- Hypoglycemia
- Sponsor
- Zealand Pharma
- Enrollment
- 42
- Locations
- 5
- Primary Endpoint
- Time to Plasma Glucose Recovery
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Exclusion Criteria
- •Females who are pregnant according to a positive urine pregnancy test, actively attempting to get pregnant, or are lactating
- •Known or suspected allergy to trial product(s) or related products
- •History of anaphylaxis or symptoms of severe systemic allergy (such as angioedema)
- •Previous randomization in this trial
- •History of an episode of severe hypoglycemia that required a third party assistance within a month prior to screening visit
- •History of hypoglycemic events associated with seizures or hypoglycemia unawareness in the last year prior to screening
- •History of epilepsy or seizure disorder
- •Receipt of any investigational drug within 3 months prior to screening
- •Active malignancy within the last 5 years
- •Congestive heart failure, New York Heart Association class II-IV
Arms & Interventions
GlucaGen®
Single fixed dose (s.c.injection) of GlucaGen®
Intervention: GlucaGen HypoKit
dasiglucagon
Single fixed dose (s.c.injection) of dasiglucagon
Intervention: dasiglucagon
placebo
Single fixed dose (s.c.injection) of placebo
Intervention: placebo
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Plasma Glucose Recovery(0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection)
- Pharmacokinetics: t½(0-300 minutes)
- Pharmacokinetics: CL/f(0-300 minutes)
- Pharmacokinetics: MRT(0-300 minutes)
- Pharmacokinetics: Tmax(0-300 minutes)
- Pharmacokinetics: λz(0-300 minutes)
- Plasma Glucose Changes From Baseline(0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection)
- Pharmacodynamics - Area Under the Effect Curve (0-30 Minutes)(0-30 minutes)
- Administration of Rescue IV Glucose Infusion After IMP Injection(0-45 minutes)
- Time to First IV Glucose Infusion After IMP Administration(0-45 minutes)
- Pharmacokinetics: AUC0-30 Min(0-30 minutes)
- Pharmacokinetics: AUC0-300min(0-300 minutes)
- Pharmacokinetics: AUC0-inf(0-300 minutes)
- Pharmacokinetics: Cmax(0-300 minutes)
- Pharmacokinetics: Vz/f(0-300 minutes)