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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 5
- 主要终点
- Time to Plasma Glucose Recovery
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •Current bleeding disorder, including anti-coagulant treatment
- •Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin secreting pancreas tumor)
- •Use of a daily systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this trial
- •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
- •Clinically significant abnormal electrocardiogram (ECG) at screening as judged by the investigator
- •Clinically significant illness within 4 weeks before screening, as judged by the investigator
- •Surgery or trauma with significant blood loss within the last 2 months prior to screening
- •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
- •Any condition interfering with trial participation or evaluation or that could be hazardous to the patient
- •The use of prescription or non-prescription medications known to cause QT prolongation
研究组 & 干预措施
GlucaGen®
Single fixed dose (s.c.injection) of GlucaGen®
干预措施: GlucaGen HypoKit (Drug)
dasiglucagon
Single fixed dose (s.c.injection) of dasiglucagon
干预措施: dasiglucagon (Drug)
placebo
Single fixed dose (s.c.injection) of placebo
干预措施: placebo (Drug)
结局指标
主要结局
Time to Plasma Glucose Recovery
时间窗: 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.
次要结局
- 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)