Evaluation of Efficacy and Safety of E004 in Children With Asthma

Asthma Clinical Trial

Official title:

Phase III Study of Epinephrine Inhalation Aerosol for Evaluation of Efficacy and Safety of E004 in Children With Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01460511
• Other study ID #: API-E004-CL-D
• Status: Completed
• Phase: Phase 3
• Start date: October 2011
• Est. completion date: July 2012

Study information

• Verified date: July 2018
• Source: Amphastar Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: July 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 11 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• E004 (Epinephrine Inhalation Aerosol) HFA-MDI
E004 (Epinephrine Inhalation Aerosol) HFA-MDI, 125 mcg/inhalation, 2 inhalations QID
• Placebo-HFA
Placebo-HFA, 0 mcg/inhalation, 2 inhalations QID

Locations

Country	Name	City	State
United States	Amphastar Site 5	Costa Mesa	California
United States	Amphastar Site 3	El Paso	Texas
United States	Amphastar Site 2	Medford	Oregon
United States	Amphastar Site 7	North Charleston	South Carolina
United States	Amphastar Site 8	Orange	California
United States	Amphastar Site 1	Portland	Oregon
United States	Amphastar Site 6	San Antonio	Texas
United States	Amphastar Site 4	Stockton	California

Sponsors (1)

Lead Sponsor	Collaborator
Amphastar Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Efficacy Endpoint AUC of FEV1's relative change	bronchodilator effect expressed as AUC of FEV1's relative change (from the same day baseline) versus time, defined as AUC of ?FEV1%.	Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Secondary	AUC of FEV1 volume changes (AUC of change in FEV1)	determination of the change in FEV1 from baseline at visit to to post treatment at Visit 3	Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Secondary	Maximum of change in FEV1% (Fmax)	Evaluation of maximum percent change in FEV1	Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Secondary	Curves of change in FEV1, and change in FEV1%, versus time	Evaluation of curves of change in FEV1 and percent change in FEV1 over time	Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Secondary	Time to onset of bronchodilator effect (to onset), determined the time point (within 60 minutes) where FEV1 first reaches =12% above Same-Day Baseline.	Evaluation of how much time elapses (within 60 minutes), until FEV1 first reaches =12% above Same-Day Baseline.	Study Visits 1and 3 within 60 minutes post dose
Secondary	The time to peak FEV1 effect (tmax), defined as the time of Fmax.	Evaluation of how much time elapses until FEV1 reaches its peak	Study Visits 1 and 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Secondary	Duration of efficacy (duration), defined as the total length of time when ?FEV1% reaches and stays =12% above Same-Day Baseline.	Evaluation of the total length of time it takes until the change in FEV1% reaches and stays =12% above Same-Day Baseline.	Study Weeks 1and 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Secondary	Percentage of positive responders (R%), including all subjects whose Fmax reaches =12% above Same-Day Baseline.	Evaluation of what percentage of subjects are positive responders (R%), including all subjects whose Fmaxreaches =12% above Same-Day Baseline.	Study Weeks 1 and 3 within 60 minutes post dose
Secondary	Mean daily morning pre-dose Peak Expiratory Flow Rate (PEF)	Evaluation of the mean of daily morning pre-dose Expiratory Flow Rate	daily pre-dose
Secondary	Evaluation of Vital Signs	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	predose, and 3, 20, 60, 360 minutes post-dose
Secondary	12-lead ECG	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	Pre-dose and , 3, 20 and 60 minutes post-dose (Study Visits 1 and 3)
Secondary	Albuterol HFA usage for rescue relief of acute asthma symptoms	Evaluation Albuterol HFA usage for rescue relief of acute asthma symptoms	Study Visits 1, 2, and 3, within 30 min predose