Evaluation of Efficacy and Safety for Single Dose of E004 in Children With Asthma

NCT01737905 | Completed Phase 3

• 1 other identifier: API-E004-CL-D2
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 6

Brief Summary

This is a multi-center, randomized, double-blinded, placebo-controlled, crossover, single dose study in 24 pediatric patients (4-11 years old) with asthma. The entire study consists of (i) a Screening Visit and (ii) a Study Period with two (2) Study Visits. All study subjects must be properly consented, under adult supervision, and screened against the inclusion and exclusion criteria, at the Screening Visit.

Conditions

Asthma

Keywords

Asthma; Safety; Efficacy; Epinephrine; Bronchodilator; Metered dose inhaler

Outcome Measures

Primary Outcomes (1)

• Bronchodilator effect

  Bronchodilator effect expressed as AUC of FEV1's relative change from the same day baseline (pre-dose) versus time up to 3 hours, defined as AUC(0-3) of change in FEV1%. The difference of primary endpoints of E004 and Placebo will be evaluated statistically.

  up to 30 min pre-dose, postdose up to 3 hours

Secondary Outcomes (14)

• AUC analysis

  up to 30 min pre-dose, postdose up to 3 hours

• Evaluation of FEV1 volume changes

  up to 30 min pre-dose, postdose up to 3 hours

• Change in FEV1

  up to 30 min pre-dose, postdose up to 3 hours

• Time response

  up to 30 min pre-dose, postdose up to 3 hours

• Time to onset of bronchodilator effect

  up to 30 min pre-dose, postdose up to 3 hours

Study Arms (2)

Arm T

EXPERIMENTAL

Experimental arm utilizing Epinephrine HFA-MDI (E004)

Drug: Epinephrine HFA-MDI (E004)

Arm P

PLACEBO COMPARATOR

Placebo comparator arm utilizing Placebo-HFA

Drug: Placebo-HFA

Interventions

Epinephrine HFA-MDI (E004) DRUG

Single dose 125 mcg/inhalation, 2 inhalations

Arm T

Placebo-HFA DRUG

Single dose 0 mcg/inhalation, 2 inhalations

Arm P

Eligibility Criteria

• Age: 4 Years - 11 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Generally healthy male, and premenarchal female, children ages 4 - 11 years upon Screening.
• With documented asthma, requiring inhaled epinephrine or β2-agonist treatment, with or without concurrent anti-inflammatory therapies including orally inhaled corticosteroids, for at least 6-months prior to Screening.
• Being capable of performing spirometry for FEV1 measurements.
• Satisfying criteria of asthma stability, defined as no significant changes in asthma therapy (with the exception of switching LABA to SABA, adjustment of ICor SABA, etc, per investigator discretion) and no asthma-related hospitalization or emergency room visits, within 4 weeks prior to Screening.
• Can tolerate withholding treatment with inhaled bronchodilators and other allowed medications for the minimum washout periods indicated in Appendix II prior to the Screening Baseline FEV1 testing.
• Demonstrating a Mean Screening Baseline FEV1 (MSBF) that is 50.0% - 90% of Polgar predicted normal value.
• Demonstrating an Airway Reversibility, i.e., FEV1 values ≥12% increase based upon volume compared with MSBF, within 30 min after 2 inhalations (440 mcg, epinephrine base) of previously marketed Epinephrine CFC-MDI, labeled "For Investigational Use Only". There will be up to 5 reversibility time points, each with up to 5 maneuvers that can be conducted anytime within 30 min post-dose.
• Demonstrating satisfactory techniques in the use of a metered-dose inhaler (MDI).
• Has been properly consented to participate in this study.

You may not qualify if:

• Any current or past medical conditions that, per investigator discretion, might significantly affect pharmacodynamic responses to the study drugs, such as significant systemic or respiratory diseases (e.g., cystic fibrosis, bronchiectasis, active tuberculosis, emphysema, nonreversible pulmonary diseases), other than asthma.
• Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, or malignant diseases.
• Known intolerance or hypersensitivity to any component of the study drugs (i.e., Epinephrine, HFA-134a, CFC-12, CFC-114, polysorbate-80, thymol, ethanol, ascorbic acid, nitric acid, and hydrochloric acid), as well as the rescue Albuterol HFA inhalers (i.e., Albuterol, HFA-134a, ethanol, and oleic acid).
• Recent infection of the upper respiratory tract (within 2 weeks), or lower respiratory tract (within 4 weeks), before screening.
• Use of prohibited medications per Appendix II.
• Having been on other investigational drug/device studies in the last 30 days prior to screening.

Sponsors & Collaborators

• Amphastar Pharmaceuticals, Inc.: lead

Study Sites (6)

West Coast Clinical Trials Global

Cypress, California, 90630, United States

Location

The Clinical Research Institute of Southern Oregn, PC

Medford, Oregon, 97504, United States

Location

Transitional Clinical Research, Inc. Allergy Associates Research Center

Portland, Oregon, 97202, United States

Location

Western Sky Medical

El Paso, Texas, 79903, United States

Location

Sylvana Research Assocaites

San Antonio, Texas, 78229, United States

Location

ASTHMA, Inc. Clinical Research Center

Seattle, Washington, 98115, United States

Location

Related Publications (7)

• 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

• Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999 Jan;159(1):179-87. doi: 10.1164/ajrccm.159.1.9712108.

  PMID: 9872837 BACKGROUND

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Selina Su, MPH

  Amphastar Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2012
• First Posted: November 30, 2012
• Study Start: October 1, 2012
• Primary Completion: March 1, 2013
• Study Completion: December 1, 2013
• Last Updated: March 11, 2016

Record last verified: 2016-02

Locations

US (6)