Epinephrine Inhalation Aerosol USP, a HFA-MDI Study for Assessment of Pharmacokinetics

NCT01188577 | Completed Phase 1 Results

• 1 other identifier: API-E004-CL-B2
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

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 for a more thorough evaluation of the E004 Pharmacokinetics. Safety of E004 will also be evaluated, under augmented dose conditions.

Conditions

Asthma; Bronchospasm; Wheezing; Shortness of Breath

Keywords

asthma; bronchospasm; wheezing; shortness of breath

Outcome Measures

Primary Outcomes (6)

• Baseline Concentration (C0) of 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.

  0 to 30 minutes prior to dosing

• Peak Concentration (Cmax) of 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), 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

  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

  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

  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

  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

Study Arms (2)

Epinephrine Inhalation Aerosol, HFA

EXPERIMENTAL

Experimental treatment of 10 inhalations of 125 mcg epinephrine base propelled by HFA 134a

Drug: Epinephrine Inhalation Aerosol, HFA

Epinephrine Inhalation Aerosol, CFC

ACTIVE COMPARATOR

Epinephrine Inhalation Aerosol, CFC propelled, 220 mcg/inhalation , 10 inhalations

Drug: Epinephrine Inhalation Aerosol

Interventions

Epinephrine Inhalation Aerosol, HFA DRUG

10 inhalations of epinephrine inhalation aerosol, 125 mcg/inhalation

Also known as: HFA epinephrine inhalation aerosol, 125 mcg/inhalation

Epinephrine Inhalation Aerosol, HFA

Epinephrine Inhalation Aerosol DRUG

Epinephrine Inhalation Aerosol, 220 mcg/ inhalation, 10 inhalations

Also known as: Primatene Mist, Epinephrine Inhalation Aerosol, USP

Epinephrine Inhalation Aerosol, CFC

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amphastar Pharmaceuticals, Inc.: lead

Study Sites (1)

Amphastar Site 0035

Cypress, California, 90630, United States

Location

Related Publications (9)

• 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.

  PMID: 2019665 BACKGROUND

• 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.

  PMID: 16400891 BACKGROUND

• 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.

  PMID: 3780129 BACKGROUND

• 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.

  PMID: 10919679 BACKGROUND

• 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.

  PMID: 10936150 BACKGROUND

• 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.

  PMID: 11061773 BACKGROUND

• 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.

  PMID: 10535697 BACKGROUND

• 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.

  PMID: 9616533 BACKGROUND

• 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.

  PMID: 32423275 DERIVED

MeSH Terms

Conditions

Asthma; Bronchial Spasm; Respiratory Sounds; Dyspnea

Interventions

Inhalation; Epinephrine

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Respiration Disorders

Intervention Hierarchy (Ancestors)

Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Stephen A. Campbell, Esq.
• Organization: Amphastar Pharmaceuticals, Inc.

stephenc@amphastar.com

(909) 980-9484

Study Officials

• Medical Director

  Amphastar Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2010
• First Posted: August 25, 2010
• Study Start: August 1, 2010
• Primary Completion: September 1, 2010
• Study Completion: January 1, 2011
• Last Updated: July 25, 2017
• Results First Posted: October 24, 2014

Record last verified: 2017-06

Locations

US (1)