Phase I/II Study Epinephrine Inhalation Aerosol USP, an HFA-MDI Clinical Study-B for Assessment of Pharmacokinetics
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Baseline Concentration (C0) of Labeled Epinephrine Total Epinephrine
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), in healthy male and female adult volunteers. Safety of E004 will also be evaluated, under augmented dose conditions.
详细描述
This study is a randomized, evaluator-blind, single dose, three-arm, crossover, PK study, to be conducted in ~18 healthy, male and female, adult volunteers. PK will be studied at two dose strengths (Arm T1 and Arm T2). A currently marketed, non-labeled, Epinephrine CFC-MDI will be used as a Reference Control (Arm C).
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At the Screening Visit and the beginning of each Study Visit, each subject will be trained on the correct self-administration of MDI. The following three randomized treatments will be self-administered, at three Study Visits:
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Treatment T1: Ten (10) inhalations of the low dose E004(125 mcg/inhalation), totaling 1.25 mg of epinephrine;
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Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine;
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Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation, totaling 2.2 mg of epinephrine base equivalent).
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PK blood samples will be taken from a vein at scheduled time points.
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Safety parameters and adverse drug events, if any, will be monitored and documented at each study visit. An End-of-Study (EOS) safety evaluation will be conducted.
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, Investigator, 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, male and female adults, 18-30 yrs of age at Screening;
- •Having no clinically significant respiratory, cardiovascular and other systemic or organic illnesses, per investigator discretion;
- •Women of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control;
- •Having properly consented and satisfied all other inclusion/exclusion criteria as required for this protocol.
- •Other criteria apply.
排除标准
- •A recent or significant smoking history;
- •Use of prohibited drugs or failure to observe the drug washout restrictions;
- •Having been on other investigational drug/device studies in the last 30 days prior to Screening.
- •Other criteria apply
研究组 & 干预措施
Treatment C
Active comparator arm utilizing marketed Primatene Mist with CFC propellant at the labeled dose.
干预措施: epinephrine inhalation aerosol (Drug)
Treatment 1
T1 is HFA propelled epinephrine inhalation aerosol 125 mcg/inhalation
干预措施: epinephrine inhalation aerosol (Drug)
Treatment 2
HFA propelled epinephrine inhalation aerosol, 160 mcg/inhalation
干预措施: epinephrine inhalation aerosol (Drug)
结局指标
主要结局
Baseline Concentration (C0) of Labeled Epinephrine 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.
Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6])
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), 5, 15, 30, 45, 60, 90, 120, 180, 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.
Peak Concentration (Cmax) 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), 5, 15, 30, 45, 60, 90, 120, 180, 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.
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), 5, 15, 30, 45, 60, 90, 120, 180, 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) 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), 5, 15, 30, 45, 60, 90, 120, 180, 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 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), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method.
次要结局
- Vital Signs: Systolic Blood Pressure (SBP)(Pre-dose (baseline) to 360 minutes post-dose)
- Vital Signs: Diastolic Blood Pressure (DBP)(Pre-dose (baseline) to 360 minutes post-dose)
- Vital Signs: Heart Rate (HR)(Pre-dose (baseline) to 360 minutes post-dose)
- ECG: QT Interval(Pre-dose (baseline) to 360 minutes post-dose)
- ECG: QTc Interval(Pre-dose (baseline) to 360 minutes post-dose)
- Hand Tremor Scores(Pre-dose (baseline) to 360 minutes post-dose)
- Number of Subjects With Significant Changes in Physical Examination(Approximately 6 weeks)
- Number of Subjects With Significant Changes in Laboratory Tests(Approximately 6 weeks)
- Serum Glucose Levels(Pre-dose (baseline) to 360 minutes post-dose)
- Serum Potassium Levels(Pre-dose (baseline) to 360 minutes post-dose)