- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01143051
Pharmacokinetics (PK) Study of Epinephrine Inhalation Aerosol in Healthy Volunteers
Phase I/II Study Epinephrine Inhalation Aerosol USP, an HFA-MDI Clinical Study-B for Assessment of Pharmacokinetics
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Cypress, California, United States, 90630
- Amphastar Location 1
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Treatment C
Active comparator arm utilizing marketed Primatene Mist with CFC propellant at the labeled dose.
|
Single dose 220 mcg/inhalation, 10 inhalations
Other Names:
HFA propelled epinephrine inhalation aerosol, 125 mcg/inhalation, 10 inhalations
Other Names:
HFA propelled epinephrine inhalation aerosol, 160 mcg/inhalation, 10 inhalations
Other Names:
|
EXPERIMENTAL: Treatment 1
T1 is HFA propelled epinephrine inhalation aerosol 125 mcg/inhalation
|
Single dose 220 mcg/inhalation, 10 inhalations
Other Names:
HFA propelled epinephrine inhalation aerosol, 125 mcg/inhalation, 10 inhalations
Other Names:
HFA propelled epinephrine inhalation aerosol, 160 mcg/inhalation, 10 inhalations
Other Names:
|
EXPERIMENTAL: Treatment 2
HFA propelled epinephrine inhalation aerosol, 160 mcg/inhalation
|
Single dose 220 mcg/inhalation, 10 inhalations
Other Names:
HFA propelled epinephrine inhalation aerosol, 125 mcg/inhalation, 10 inhalations
Other Names:
HFA propelled epinephrine inhalation aerosol, 160 mcg/inhalation, 10 inhalations
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Baseline Concentration (C0) of Labeled Epinephrine Total Epinephrine
Time Frame: 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.
|
0 to 30 minutes prior to dosing
|
Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6])
Time Frame: 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.
|
Pre-dose to 6 hours post-dose
|
Peak Concentration (Cmax) for Total Epinephrine From Time Zero to 6 Hours Post-dose
Time Frame: 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.
|
Pre-dose to 6 hours post-dose
|
Time to Reach Peak Concentration (Tmax) for Total Epinephrine
Time Frame: 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.
|
Pre-dose to 6 hours post-dose
|
Half-life (t1/2) for Total Epinephrine
Time Frame: 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.
|
Pre-dose to 6 hours post-dose
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
Time Frame: 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.
|
Pre-dose to 6 hours post-dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Vital Signs: Systolic Blood Pressure (SBP)
Time Frame: Pre-dose (baseline) to 360 minutes post-dose
|
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.
|
Pre-dose (baseline) to 360 minutes post-dose
|
Vital Signs: Diastolic Blood Pressure (DBP)
Time Frame: Pre-dose (baseline) to 360 minutes post-dose
|
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.
|
Pre-dose (baseline) to 360 minutes post-dose
|
Vital Signs: Heart Rate (HR)
Time Frame: Pre-dose (baseline) to 360 minutes post-dose
|
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.
|
Pre-dose (baseline) to 360 minutes post-dose
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ECG: QT Interval
Time Frame: Pre-dose (baseline) to 360 minutes post-dose
|
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.
|
Pre-dose (baseline) to 360 minutes post-dose
|
ECG: QTc Interval
Time Frame: Pre-dose (baseline) to 360 minutes post-dose
|
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.
|
Pre-dose (baseline) to 360 minutes post-dose
|
Serum Glucose Levels
Time Frame: Pre-dose (baseline) to 360 minutes post-dose
|
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.
|
Pre-dose (baseline) to 360 minutes post-dose
|
Serum Potassium Levels
Time Frame: Pre-dose (baseline) to 360 minutes post-dose
|
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.
|
Pre-dose (baseline) to 360 minutes post-dose
|
Hand Tremor Scores
Time Frame: Pre-dose (baseline) to 360 minutes post-dose
|
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.
|
Pre-dose (baseline) to 360 minutes post-dose
|
Number of Subjects With Significant Changes in Physical Examination
Time Frame: Approximately 6 weeks
|
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.
|
Approximately 6 weeks
|
Number of Subjects With Significant Changes in Laboratory Tests
Time Frame: Approximately 6 weeks
|
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.
|
Approximately 6 weeks
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Respiratory Tract Diseases
- Immune System Diseases
- Respiration Disorders
- Lung Diseases
- Hypersensitivity, Immediate
- Bronchial Diseases
- Lung Diseases, Obstructive
- Respiratory Hypersensitivity
- Hypersensitivity
- Respiratory Aspiration
- Asthma
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Adrenergic alpha-Agonists
- Adrenergic Agonists
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Adrenergic beta-Agonists
- Sympathomimetics
- Vasoconstrictor Agents
- Mydriatics
- Epinephrine
- Racepinephrine
- Epinephryl borate
Other Study ID Numbers
- API-E004-CL-B
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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