Assessment and Evaluation of Pharmacokinetic Profile of E004 in Healthy Adults (A Randomized, Evaluator-Blind, Single-Dose, Two Arm, Crossover, PK Study in Healthy Volunteers)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Calculation and Comparison of relative Bioavailability of 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), 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 to complement an earlier PK study, API-E004-CL-B, for a more thorough evaluation of the E004 PK. Safety of E004 will also be evaluated.
详细描述
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 previously marketed Epinephrine CFC-MDI, labeled "For Investigational Use Only" will be used as a Reference Control (Arm C).
The main features of the study design are:
(1) All candidates must be screened and must satisfy all enrollment criteria. All enrolled subjects will participate in two Study Visits, corresponding to two randomized treatments. Each Study Visit consists of a pre-dose baseline assessment and a post-dose evaluation for 6 hours.
(2) It is important to minimize physical and psychological disturbances to the endogenous epinephrine concentrations in the study subjects, before and during the study visits. All subjects must maintain a reclining or recumbent resting position during the entire Study Visit, with physical activities restricted to a minimum necessity for bathroom trips and study activities. Caffeine-containing (including de-caffeinated) foods or beverages are prohibited. Physical exercise, unnecessary physical activities, and video games are prohibited throughout the study visit.
(3)At the Screening Visit and the beginning of each Study Visit, each subject will be trained on the correct self-administration of MDI, using a simulation MDI unit that contains no active drug. The following two randomized treatments will be self-administered at two Study Visits:
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
- Single (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;
- •Body weight greater than or equal to 50 kg for men and greater than or equal to 45 kg for women, and BMI within the range of 18.5 - 30.0 kg/m2 inclusive
- •Sitting blood pressure less than or equal to 135/90 mmHg;
- •Demonstrating negative alcohol/drug screen tests;
- •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;
- •Having properly consented and satisfied all other inclusion/exclusion criteria as required for this protocol.
排除标准
- •A smoking history of more than or equal to 10 pack-years, or having smoked within 6 months prior to Screening;
- •Upper respiratory tract infections within 2 weeks, or lower respiratory tract infection within 4 weeks, prior to Screening
- •Any current or recent respiratory conditions that, per investigator discretion, might significantly affect pharmacodynamic response to the study drugs, including but not limited to: asthma, COPD, cystic fibrosis, bronchiectasis, tuberculosis, emphysema, etc.
- •Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine (including diabetes), psychiatric, neoplastic or other illnesses that in the opinion of the investigator could impact on the conduct, safety and evaluation of the study
- •Known intolerance or hypersensitivity to any of the study MDI ingredients (i.e., epinephrine, HFA-134a, CFC-12, CFC-114, polysorbate-80, ethanol, thymol, nitric acid and ascorbic acid)
- •Use of prohibited drugs or failure to observe the drug washout restrictions
- •Having been on other investigational drug/device studies, or donated blood, in the last 30 days prior to Screening.
研究组 & 干预措施
Arm T-Epinephrine Inhalation Aerosol HFA
Experimental arm utilizing Epinephrine HFA-MDI (E004)
干预措施: Arm T Epinephrine Inhalation Aerosol HFA, 125 mcg, 1 inhalation (Drug)
Arm C-Epinephrine Inhalation Aerosol CFC
Active comparator arm utilizing Epinephrine CFC-MDI
干预措施: Arm C-Epinephrine Inhalation Aerosol CFC (Drug)
结局指标
主要结局
Calculation and Comparison of relative Bioavailability of Epinephrine
时间窗: up to 30 min predose and at 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240 and 360 minutes postdose
Blood PK samples will be collected at each visit for both study arms, then the Area Under the Curve (s) will be calculated for both arms and compared to give relative bioavailability
次要结局
- Vital Signs(up to 30 min predose and at 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240 and 360 minutes postdose)
- 12-lead ECG (Routine and QT/QTc analysis)(up to 30 min predose and at 5, 10, 15, 20, 30, 60, 120, and 360 minutes postdose)
- Physical Examinations(up to 30 min predose and after 360 min post last dose)
- Lab tests(up to 30 min predose)