Evaluation of Efficacy and Safety of E004 in Children With Asthma

Study Description

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Brief Summary:

This is a multi-center, randomized, double-blinded, placebo-controlled, parallel, 4-week study in 60 pediatric patients (4-11 years old) with asthma, comparing E004 with Placebo HFA-MDI in pediatric patients who are 4-11 years of age with asthma.

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: Epinephrine Inhalation Aerosol	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	70 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Phase III Study of Epinephrine Inhalation Aerosol for Evaluation of Efficacy and Safety of E004 in Children With Asthma
Study Start Date :	October 2011
Actual Primary Completion Date :	March 2012
Actual Study Completion Date :	July 2012

Arms and Interventions

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Arm	Intervention/treatment
Placebo Comparator: Placebo; E004 formulation without active ingredient	Drug: Epinephrine Inhalation Aerosol; 250 mcg (2 inhalations), 4 times daily
Experimental: Active; E004 formulation of epinephrine inhalation aerosol HFA	Drug: Epinephrine Inhalation Aerosol; 250 mcg (2 inhalations), 4 times daily

Outcome Measures

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Primary Outcome Measures :

1. Primary Efficacy Endpoint AUC of FEV1's relative change [ Time Frame: Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose ]
   bronchodilator effect expressed as AUC of FEV1's relative change (from the same day baseline) versus time, defined as AUC of ΔFEV1%.

Secondary Outcome Measures :

1. AUC of FEV1 volume changes (AUC of change in FEV1) [ Time Frame: Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose ]
   determination of the change in FEV1 from baseline at visit to to post treatment at Visit 3
2. Maximum of change in FEV1% (Fmax) [ Time Frame: Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose ]
   Evaluation of maximum percent change in FEV1
3. Curves of change in FEV1, and change in FEV1%, versus time [ Time Frame: Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose ]
   Evaluation of curves of change in FEV1 and percent change in FEV1 over time
4. Time to onset of bronchodilator effect (to onset), determined the time point (within 60 minutes) where FEV1 first reaches ≥12% above Same-Day Baseline. [ Time Frame: Study Visits 1and 3 within 60 minutes post dose ]
   Evaluation of how much time elapses (within 60 minutes), until FEV1 first reaches ≥12% above Same-Day Baseline.
5. The time to peak FEV1 effect (tmax), defined as the time of Fmax. [ Time Frame: Study Visits 1 and 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose ]
   Evaluation of how much time elapses until FEV1 reaches its peak
6. Duration of efficacy (duration), defined as the total length of time when ΔFEV1% reaches and stays ≥12% above Same-Day Baseline. [ Time Frame: Study Weeks 1and 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose ]
   Evaluation of the total length of time it takes until the change in FEV1% reaches and stays ≥12% above Same-Day Baseline.
7. Percentage of positive responders (R%), including all subjects whose Fmax reaches ≥12% above Same-Day Baseline. [ Time Frame: Study Weeks 1 and 3 within 60 minutes post dose ]
   Evaluation of what percentage of subjects are positive responders (R%), including all subjects whose Fmaxreaches ≥12% above Same-Day Baseline.
8. Mean daily morning pre-dose Peak Expiratory Flow Rate (PEF) [ Time Frame: daily pre-dose ]
   Evaluation of the mean of daily morning pre-dose Expiratory Flow Rate
9. Evaluation of Vital Signs [ Time Frame: predose, and 3, 20, 60, 360 minutes post-dose ]
   Monitoring of vital signs (SBP/DBP, and heart rate) at the Screening Visit (Baseline and 30 min post-dose), and at the baseline, 3, 20, 60 and 360 minute time points during the study
10. 12-lead ECG [ Time Frame: Pre-dose and , 3, 20 and 60 minutes post-dose (Study Visits 1 and 3) ]
    Recording of 12-lead ECG (Routine and QT/QTc) at Screening Visit Baseline, and at the baseline, 3, 20 and 60 minute time points during Study Visits 1 and 3
11. Albuterol HFA usage for rescue relief of acute asthma symptoms [ Time Frame: Study Visits 1, 2, and 3, within 30 min predose ]
    Evaluation Albuterol HFA usage for rescue relief of acute asthma symptoms

Eligibility Criteria

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Ages Eligible for Study:	4 Years to 11 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Generally healthy male, and premenarchal female, children aged 4 - 11 years upon Screening.
• With documented asthma, requiring inhaled epinephrine or beta2-agonist treatment, with or without concurrent anti-inflammatory therapies for at least 6-months prior to Screening.
• Being capable of performing spirometry for FEV1
• Satisfying criteria of asthma
• Can tolerate withholding treatment with inhaled bronchodilators and other allowed medications for the minimum washout periods
• Demonstrating a Screening Baseline FEV1 that is 50 - 90% of Polgar predicted normal value.
• Demonstrating an Airway Reversibility,
• Demonstrating satisfactory techniques in the use of a metered-dose inhaler (MDIs) and a hand held peak expiratory flow meter, after training.
• Has been properly consented to participate in this study.

Exclusion Criteria:

• Any current or past medical conditions that, per investigator discretion, might significantly affect pharmacodynamic responses to the study drugs
• Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, or malignant diseases.
• Known intolerance or hypersensitivity to any component of the study drugs
• Recent infection of the respiratory tract
• Use of prohibited medications
• Having been on other investigational drug/device studies in the last 30 days prior to screening.

Contacts and Locations

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Locations

United States, California
Amphastar Site 5
Costa Mesa, California, United States, 92626
Amphastar Site 8
Orange, California, United States, 92868
Amphastar Site 4
Stockton, California, United States, 95207
United States, Oregon
Amphastar Site 2
Medford, Oregon, United States, 97504
Amphastar Site 1
Portland, Oregon, United States, 97202
United States, South Carolina
Amphastar Site 7
North Charleston, South Carolina, United States, 29406
United States, Texas
Amphastar Site 3
El Paso, Texas, United States, 79903
Amphastar Site 6
San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Amphastar Pharmaceuticals, Inc.

Investigators

Study Chair:	John Gao, M.D.	Amphastar Pharmaceuticals, Inc.

More Information

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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.

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.

Warren JB, Doble N, Dalton N, Ewan PW. Systemic absorption of inhaled epinephrine. Clin Pharmacol Ther. 1986 Dec;40(6):673-8.

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.

Responsible Party:	Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT01460511 History of Changes
Other Study ID Numbers:	API-E004-CL-D
First Posted:	October 27, 2011
Last Update Posted:	July 12, 2012
Last Verified:	July 2012

Keywords provided by Amphastar Pharmaceuticals, Inc.:

Mild bronchial asthma

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Epinephrine; Racepinephrine; Epinephryl borate; Adrenergic alpha-Agonists; Adrenergic Agonists	Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Adrenergic beta-Agonists; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Asthmatic Agents; Respiratory System Agents; Mydriatics; Sympathomimetics; Vasoconstrictor Agents