Epinephrine Inhalation Aerosol USP, an HFA-MDI CLINICAL STUDY-B2 FOR ASSESSMENT OF PHARMACOKINETICS (A Randomized, Evaluator-Blind, Single-Dose, Two Arm, Crossover, PK Study in Healthy Volunteers)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Peak Concentration (Cmax) of Total Epinephrine From Time Zero to 6 Hours Post-dose
研究概览
简要总结
This study examines the pharmacokinetic profile of Armstrong's proposed Epinephrine Inhalation Aerosol USP, an HFA-MDI (E004), using a stable isotope deuterium-labeled epinephrine (epinephrine-d3) to differentiate the administered drug from the endogenous epinephrine, in healthy male and female adult volunteers. The current study is designed for a more thorough evaluation of the E004 Pharmacokinetics. Safety of E004 will also be evaluated, under augmented dose conditions.
详细描述
E004 is formulated with epinephrine free base as the active ingredient, and hydrofluoroalkane (HFA-134a) as the propellant.
In order to differentiate the inhaled epinephrine from the fluctuating background of endogenous epinephrine 1, a stable-isotope deuterium (2H) labeled epinephrine (epinephrine-d3) preparation will be used to formulate E004 inhalers, denoted as E004-d3. PK of E004 at 125 mcg of epinephrine-d3 per inhalation, will be compared to that of the currently marketed, non-labeled, Epinephrine-CFC MDI as the Reference Control (220 mcg per inhalation).
This study is a randomized, evaluator-blind, single dose, two-arm, crossover, PK study, to be conducted in ~18 healthy, male and female, adult volunteers. PK will be studied using E004-d3 at 125 mcg per inhalation (Arm T). A currently marketed, non-labeled, Epinephrine CFC-MDI will be used as a Reference Control (Arm C).
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
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 30 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Generally healthy at screening;
- •No clinically significant respiratory, cardiovascular and other systemic or organic illnesses;
- •Body weight ≥ 50 kg for men and ≥ 45 kg for women,
- •Sitting blood pressure ≤ 135/90 mm Hg;
- •Demonstrating negative HIV, HBsAg and HCV-Ab screen tests;
- •Women of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control;
- •Properly consented
- •Other criteria apply
排除标准
- •A smoking history of ≥10 pack-years, or having smoked within 6 months;
- •Upper respiratory tract infections within 2 wk, or lower respiratory tract infection within 4 wk, prior to Screening;
- •Any current or recent respiratory conditions that might significantly affect pharmacodynamic response to the study drugs;
- •Known intolerance or hypersensitivity to the study MDI ingredients;
- •Having been on other investigational studies, or donated blood, in the last 30 days;
- •Other Criteria Apply
研究组 & 干预措施
Epinephrine Inhalation Aerosol, CFC
Epinephrine Inhalation Aerosol, CFC propelled, 220 mcg/inhalation , 10 inhalations
干预措施: Epinephrine Inhalation Aerosol (Drug)
Epinephrine Inhalation Aerosol, HFA
Experimental treatment of 10 inhalations of 125 mcg epinephrine base propelled by HFA 134a
干预措施: Epinephrine Inhalation Aerosol, HFA (Drug)
结局指标
主要结局
Peak Concentration (Cmax) of Total Epinephrine From Time Zero to 6 Hours Post-dose
时间窗: Pre-dose to 6 hours post-dose
Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Peak (maximum) concentration (Cmax) is the highest concentration of epinephrine measured in plasma during the treatment period.
Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6]) for Total Epinephrine
时间窗: Pre-dose to 6 hours post-dose
Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Area under the curve from time zero to 6 hours post-dose (AUC\[0-6\]) was calculated using the trapezoidal rule.
Baseline Concentration (C0) of Total Epinephrine
时间窗: 0 to 30 minutes prior to dosing
Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at Baseline (prior to dosing) in each treatment period following a specified washout period (3-14 days), and were analyzed using an established analysis method. Baseline concentration (C0) is the concentration of epinephrine measured in the plasma at this time point.
Time to Reach Peak Concentration (Tmax) for Total Epinephrine
时间窗: Pre-dose to 6 hours post-dose
Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Tmax is the amount of time it takes for epinephrine to reach peak concentration in plasma during the treatment period.
Half-life (t1/2) of Total Epinephrine
时间窗: Pre-dose to 6 hours post-dose
Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Half-life (t1/2) is the amount of time it takes for epinephrine to decrease to half the peak concentration in plasma during the treatment period.
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
时间窗: Pre-dose to 6 hours post-dose
Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method.
次要结局
未报告次要终点