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.
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). * 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: * Treatment T1: Ten (10) inhalations of the low dose E004(125 mcg/inhalation), totaling 1.25 mg of epinephrine; * Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine; * Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation, totaling 2.2 mg of epinephrine base equivalent). * PK blood samples will be taken from a vein at scheduled time points. * 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
24
Single dose 220 mcg/inhalation, 10 inhalations
HFA propelled epinephrine inhalation aerosol, 125 mcg/inhalation, 10 inhalations
HFA propelled epinephrine inhalation aerosol, 160 mcg/inhalation, 10 inhalations
Amphastar Location 1
Cypress, California, United States
Baseline Concentration (C0) of Labeled Epinephrine Total Epinephrine
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 frame: 0 to 30 minutes prior to dosing
Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6])
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.
Time frame: Pre-dose to 6 hours post-dose
Peak Concentration (Cmax) for Total Epinephrine From Time Zero 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 frame: Pre-dose to 6 hours post-dose
Time to Reach Peak Concentration (Tmax) for Total Epinephrine
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.
Time frame: Pre-dose to 6 hours post-dose
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Half-life (t1/2) for Total Epinephrine
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.
Time frame: Pre-dose to 6 hours post-dose
Concentration vs. Time for Total Epinephrine From Time Zero 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.
Time frame: Pre-dose to 6 hours post-dose
Vital Signs: Systolic Blood Pressure (SBP)
Subject vital signs, i.e., blood pressure and heart rate, were measured prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.
Time frame: Pre-dose (baseline) to 360 minutes post-dose
Vital Signs: Diastolic Blood Pressure (DBP)
Subject vital signs, i.e., blood pressure and heart rate, were measured prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.
Time frame: Pre-dose (baseline) to 360 minutes post-dose
Vital Signs: Heart Rate (HR)
Subject vital signs, i.e., blood pressure and heart rate, were measured prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.
Time frame: Pre-dose (baseline) to 360 minutes post-dose
ECG: QT Interval
Subject QT and QTc Intervals were recorded using a 12-Lead ECG prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.
Time frame: Pre-dose (baseline) to 360 minutes post-dose
ECG: QTc Interval
Subject QT and QTc Intervals were recorded using a 12-Lead ECG prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.
Time frame: Pre-dose (baseline) to 360 minutes post-dose
Serum Glucose Levels
Blood samples used to measure subject serum glucose and potassium levels were collected prior to study drug dosing (baseline) and up to 360 minutes post-dose.
Time frame: Pre-dose (baseline) to 360 minutes post-dose
Serum Potassium Levels
Blood samples used to measure subject serum glucose and potassium levels were collected prior to study drug dosing (baseline) and up to 360 minutes post-dose.
Time frame: Pre-dose (baseline) to 360 minutes post-dose
Hand Tremor Scores
Subjects evaluated hand tremor experiences using a scale from 0 to 3 (0: No tremor; 1: Mild, perceivable; 2: Moderate, observable; and 3: Severe, interfering with hand activities). Hand tremors were evaluated prior to study drug dosing (baseline) and up to 360 minutes post-dose.
Time frame: Pre-dose (baseline) to 360 minutes post-dose
Number of Subjects With Significant Changes in Physical Examination
Physical examinations were performed as a part of Screening and End-of-Study (EOS) procedures. This outcome is a count of the number of subjects that showed a clinically significant change in the EOS physical examination compared to the Screening Visit.
Time frame: Approximately 6 weeks
Number of Subjects With Significant Changes in Laboratory Tests
Laboratory tests (CBC, serum comprehensive metabolic panel, urinalysis, and urinary pregnancy test for women of childbearing potential) were performed as a part of Screening and End-of-Study (EOS) procedures. This outcome is a count of the number of subjects that showed a clinically significant change in the EOS laboratory tests compared to the Screening Visit.
Time frame: Approximately 6 weeks