Assessment of Intranasal Glucagon in Children and Adolescents With Type 1 Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 7
- 主要终点
- Area Under the Effect Concentration Time Curve (AUEC0-1.5) of Baseline-Adjusted Glucose From Time Zero up to 90 Minutes
研究概览
简要总结
The purpose of this study was to assess how glucagon administered nasally, using a nasal dosing delivery device, works in children and adolescents compared with commercially-available glucagon given by injection. In addition, the safety and tolerability of glucagon given nasally was evaluated.
详细描述
This study was conducted to permit determination of appropriate dose level(s) for pediatric use based on the safety observations and results of glucagon and glucose assays.
Each participant 12 to less than 17 years of age underwent two visits in random order and received glucagon nasal powder once and commercially available glucagon (GlucaGen, Novo Nordisk) by intramuscular (IM) injection once. Participants 4 to less than 12 years were randomly assigned to have either 1 visit with commercially available glucagon (GlucaGen, Novo Nordisk) by IM injection OR to have 2 visits with a 2.0 milligram (mg) dose of glucagon nasal powder administered during one visit and a 3.0 mg dose of glucagon nasal powder administered during the other visit. For those randomized to complete two research dosing visits, the dose of glucagon nasal powder given during each visit was masked to the participant and study personnel.
Glucagon was administered after glucose was lowered to <80 mg/dL using insulin if necessary on the dosing day. Participants were treated with either glucagon given nasally (either 2.0 mg or 3.0 mg for participants 4 to less than 12 years of age or 3.0 mg for those 12 to less than 17 years of age) or by intramuscular (IM) injection (1 mg for those 55 pounds [lbs] or more and 0.5 mg for those weighing less than 55 lbs) in the quadriceps muscle of the leg.
Blood glucose levels and adverse events were carefully monitored for 90 minutes post-dosing. After a wash-out period of 7 days or more, participants 12 to less than 17 years of age returned to the clinic and the procedure was repeated with each participant crossed over to the other treatment. Participants 4 to less than 12 years assigned to have 2 dosing visits returned to clinic for repeated procedures and received alternate dose of nasal glucagon (NG). Participants 4 to less than 12 years assigned to a single dosing visit did not return for a second dosing visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
IM and NG arms are open labeled. NG cohorts, 2mg and 3mg, are quadruple blinded.
入排标准
- 年龄范围
- 4 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be eligible, the following inclusion criteria were met:
- •History of type 1 diabetes and receiving daily insulin therapy from the time of diagnosis for at least 12 months
- •At least 4 years of age and less than 17 years
- •Females must have met one of the following criteria:
- •Of childbearing potential but agreed to use an accepted contraceptive regimen as described in the study procedure manual throughout the entire duration of the study (from screening until study completion)
- •Of non-childbearing potential, defined as a female who had a hysterectomy or tubal ligation, was clinically considered infertile or had not yet reached menarche
- •In good general health with no conditions that could have influenced the outcome of the trial, and in the judgment of the Investigator was a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations
- •Willingness to adhere to the study requirements
排除标准
- •An individual was not eligible if any of the following exclusion criteria were present:
- •Females who were pregnant according to a positive urine pregnancy test, actively attempting to get pregnant, or were lactating
- •History of hypersensitivity to glucagon or any related products or severe hypersensitivity reactions (such as angioedema) to any drugs
- •Presence of cardiovascular, gastrointestinal, liver or kidney disease, or any other conditions which in the judgment of the investigator could have interfered with the absorption, distribution, metabolism or excretion of drugs or could potentiate or predispose to undesired effects
- •History of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma
- •History of an episode of severe hypoglycemia (as defined by an episode that required third party assistance for treatment) in the 1 month prior to enrolling in the study
- •Use of daily systemic beta-blocker, indomethacin, warfarin or anticholinergic drugs
- •History of epilepsy or seizure disorder
- •Use of an Investigational Product in another clinical trial within the past 30 days
- •Blood donation in 3 months prior to first glucagon dosing
研究组 & 干预措施
Nasal Glucagon (NG)
Nasal glucagon (NG) doses of 2.0 mg and 3.0 mg for participants 4 to less than 12 years of age and 3.0 mg for those 12 to less than 17 years of age were administered in a nostril with a prefilled delivery device that delivered a single dose upon activation.
干预措施: Nasal Glucagon (Drug)
Intramuscular (IM) Glucagon
Participants who weighed at least 25 kilograms (kg)/55 pounds (lbs) were dosed 1 mg of IM glucagon; participants who weighed less than 25 kg/55 lbs, IM glucagon dosed with 0.5 mg
干预措施: Intramuscular Glucagon (Drug)
结局指标
主要结局
Area Under the Effect Concentration Time Curve (AUEC0-1.5) of Baseline-Adjusted Glucose From Time Zero up to 90 Minutes
时间窗: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
Maximum Change From Baseline Concentration (Cmax) of Glucagon
时间窗: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
Area Under the Curve (AUC0-1.5) of Baseline Adjusted Glucagon
时间窗: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
Maximum Concentration (Cmax) of Baseline-Adjusted Glucose
时间窗: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose
时间窗: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon
时间窗: Pre-dose; 5, 10, 15, 20, 30, 40, 60 and 90 minutes following glucagon administration
次要结局
- Nasal and Non-nasal Effects/Symptoms(Pre-dose;15, 30, 60 and 90 minutes following glucagon administration)
- Number of Participants Achieving at Least a 25 mg/dL Rise in Blood Glucose Above Nadir Level Within 30 Minutes(Pre-dose; 5, 10, 15, 20, and 30 minutes following glucagon administration)
- Time to Achieving ≥25 mg/dL Rise in Plasma Glucose Above Nadir Level Within 30 Minutes(Pre-dose; 5, 10, 15, 20, and 30 minutes following glucagon administration)