A Single Site, Randomized, Four-Way, Four-Period PK/PD Crossover Phase 1 Clinical Study in 16 Fasted Healthy Adult Volunteers Receiving 3 Dose Levels of Intranasally Administered Glucagon and One Dose Level of Glucagon Administered by Subcutaneous Injection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Number of Participants With One or More Serious Adverse Event(s) (SAEs)
研究概览
简要总结
The main purpose of this study was to evaluate the safety and tolerability of nasal glucagon (NG). The study drug was delivered into the participant's nostril (intranasally) or was given as an injection just under the skin (subcutaneously) once in each of four study periods. The study lasted about 23 days for each participant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Body mass index (BMI) greater than or equal to 20.00 and below or equal to 28.00 kg/m².
- •Light-, non- or ex-smokers.
- •Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination and/or clinical laboratory evaluations (hematology, biochemistry, ECG and urinalysis).
排除标准
- •Presence of any nose piercings.
- •History of significant hypersensitivity to glucagon or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs.
- •Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects.
- •Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease.
- •Presence of clinically significant findings on nasal examination and bilateral anterior rhinoscopy.
- •Fasting blood glucose above 5.0 millimoles per liter (mmol/L) at screening, following a 12-hour fasting period.
- •Fasting blood glucose assessed with a glucose meter above 5.5 mmol/L 0.5 hour before each dosing.
研究组 & 干预措施
Nasal Glucagon (NG) - 0.5 mg
Ng dose at 0.5 milligram (mg) administered once in one of four study periods.
干预措施: Nasal Glucagon (Drug)
NG - 1.0 mg
Ng dose at 1.0 milligram (mg) administered once in one of four study periods.
干预措施: Nasal Glucagon (Drug)
NG - 2.0 mg
Ng dose at 2.0 milligram (mg) administered once in one of four study periods.
干预措施: Nasal Glucagon (Drug)
SC Glucagon 1 mg
Subcutaneous (SC) glucagon dose of 1 mg, in one of four study periods.
干预措施: Glucagon (Drug)
结局指标
主要结局
Number of Participants With One or More Serious Adverse Event(s) (SAEs)
时间窗: Baseline through Study Completion (Day 23)
Safety and tolerability evaluated through the assessment of adverse events. A SAE (serious adverse event) was defined as any untoward medical occurrence in a clinical investigation, which did not necessarily have a causal relationship with this treatment. A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
次要结局
- Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to T (AUC[0-tlast]) of Baseline Adjusted Glucagon(Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment)
- PK: Area Under the Curve Extrapolated to Infinity (AUC[0-inf]) of Baseline Adjusted Glucagon(Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment)
- PK: Time to Maximum Concentration (Tmax) of Baseline Adjusted Glucagon(Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment)
- PK: Maximum Change From Baseline Concentration (Cmax) of Glucagon(Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment)
- Pharmacodynamics (PD): Area Under the Effect Concentration Time Curve (AUEC₀-₄) of Glucose(Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment)
- PD: Time to Maximum Concentration (Tmax) of Baseline-Adjusted Glucose(Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment)
- PD: Baseline-Adjusted Glucose Maximum Concentration (BGmax)(Day 1: -0.5, -0.25, 0, 0.08, 0.17, 0.25, 0.33, 0.5, 0.67, 1.0, 1.5, 2, 2.5, 3 and 4 hours post dose for each treatment)