- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01188577
Epinephrine Inhalation Aerosol USP, a HFA-MDI Study for Assessment of Pharmacokinetics
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)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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).
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Cypress, California, United States, 90630
- Amphastar Site 0035
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Epinephrine Inhalation Aerosol, HFA
Experimental treatment of 10 inhalations of 125 mcg epinephrine base propelled by HFA 134a
|
10 inhalations of epinephrine inhalation aerosol, 125 mcg/inhalation
Other Names:
|
Active Comparator: Epinephrine Inhalation Aerosol, CFC
Epinephrine Inhalation Aerosol, CFC propelled, 220 mcg/inhalation , 10 inhalations
|
Epinephrine Inhalation Aerosol, 220 mcg/ inhalation, 10 inhalations
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Baseline Concentration (C0) of 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
|
Peak Concentration (Cmax) of 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), 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.
|
Pre-dose to 6 hours post-dose
|
Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6]) 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), 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.
|
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), 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.
|
Pre-dose to 6 hours post-dose
|
Half-life (t1/2) of 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), 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.
|
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), 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.
|
Pre-dose to 6 hours post-dose
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Pinnas JL, Schachtel BP, Chen TM, Roseberry HR, Thoden WR. Inhaled epinephrine and oral theophylline-ephedrine in the treatment of asthma. J Clin Pharmacol. 1991 Mar;31(3):243-7. doi: 10.1002/j.1552-4604.1991.tb04969.x.
- Hendeles L, Marshik PL, Ahrens R, Kifle Y, Shuster J. Response to nonprescription epinephrine inhaler during nocturnal asthma. Ann Allergy Asthma Immunol. 2005 Dec;95(6):530-4. doi: 10.1016/S1081-1206(10)61014-9.
- Warren JB, Doble N, Dalton N, Ewan PW. Systemic absorption of inhaled epinephrine. Clin Pharmacol Ther. 1986 Dec;40(6):673-8. doi: 10.1038/clpt.1986.243.
- Cripps A, Riebe M, Schulze M, Woodhouse R. Pharmaceutical transition to non-CFC pressurized metered dose inhalers. Respir Med. 2000 Jun;94 Suppl B:S3-9.
- Dickinson BD, Altman RD, Deitchman SD, Champion HC. Safety of over-the-counter inhalers for asthma: report of the council on scientific affairs. Chest. 2000 Aug;118(2):522-6. doi: 10.1378/chest.118.2.522.
- Simons FE, Gu X, Johnston LM, Simons KJ. Can epinephrine inhalations be substituted for epinephrine injection in children at risk for systemic anaphylaxis? Pediatrics. 2000 Nov;106(5):1040-4. doi: 10.1542/peds.106.5.1040.
- Kushner DJ, Baker A, Dunstall TG. Pharmacological uses and perspectives of heavy water and deuterated compounds. Can J Physiol Pharmacol. 1999 Feb;77(2):79-88.
- Bondesson E, Friberg K, Soliman S, Lofdahl CG. Safety and efficacy of a high cumulative dose of salbutamol inhaled via Turbuhaler or via a pressurized metered-dose inhaler in patients with asthma. Respir Med. 1998 Feb;92(2):325-30. doi: 10.1016/s0954-6111(98)90116-0.
- Kerwin EM, Marrs T, Luo MZ, Zhang JY. Pharmacokinetic Study of Epinephrine Hydrofluoroalkane (Primatene MIST) Metered-Dose Inhaler. J Aerosol Med Pulm Drug Deliv. 2020 Oct;33(5):282-287. doi: 10.1089/jamp.2019.1577. Epub 2020 May 18.
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
Keywords
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Respiration Disorders
- Bronchial Diseases
- Signs and Symptoms, Respiratory
- Respiratory Sounds
- Dyspnea
- Bronchial Spasm
- 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-B2
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