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Evaluation of Efficacy and Safety of E004 in Children With Asthma

Primary Purpose

Asthma

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
E004 (Epinephrine Inhalation Aerosol) HFA-MDI
Placebo-HFA
Sponsored by
Amphastar Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma focused on measuring Mild bronchial asthma

Eligibility Criteria

4 Years - 11 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Amphastar Site 5
  • Amphastar Site 8
  • Amphastar Site 4
  • Amphastar Site 2
  • Amphastar Site 1
  • Amphastar Site 7
  • Amphastar Site 3
  • Amphastar Site 6

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

P - Placebo-HFA

T - E004 (Epinephrine Inhalation Aerosol) HFA-MDI

Arm Description

Placebo-HFA, 0 mcg/inhalation, 2 inhalations QID

E004 (Epinephrine Inhalation Aerosol) HFA-MDI, 125 mcg/inhalation, 2 inhalations QID

Outcomes

Primary Outcome Measures

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 ΔFEV1%.

Secondary Outcome Measures

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
Maximum of change in FEV1% (Fmax)
Evaluation of maximum percent change in FEV1
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
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.
The time to peak FEV1 effect (tmax), defined as the time of Fmax.
Evaluation of how much time elapses until FEV1 reaches its peak
Duration of efficacy (duration), defined as the total length of time when ΔFEV1% 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.
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.
Mean daily morning pre-dose Peak Expiratory Flow Rate (PEF)
Evaluation of the mean of daily morning pre-dose Expiratory Flow Rate
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
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
Albuterol HFA usage for rescue relief of acute asthma symptoms
Evaluation Albuterol HFA usage for rescue relief of acute asthma symptoms

Full Information

First Posted
October 24, 2011
Last Updated
July 27, 2018
Sponsor
Amphastar Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01460511
Brief Title
Evaluation of Efficacy and Safety of E004 in Children With Asthma
Official Title
Phase III Study of Epinephrine Inhalation Aerosol for Evaluation of Efficacy and Safety of E004 in Children With Asthma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
October 2011 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amphastar Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
Mild bronchial asthma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
P - Placebo-HFA
Arm Type
Placebo Comparator
Arm Description
Placebo-HFA, 0 mcg/inhalation, 2 inhalations QID
Arm Title
T - E004 (Epinephrine Inhalation Aerosol) HFA-MDI
Arm Type
Experimental
Arm Description
E004 (Epinephrine Inhalation Aerosol) HFA-MDI, 125 mcg/inhalation, 2 inhalations QID
Intervention Type
Drug
Intervention Name(s)
E004 (Epinephrine Inhalation Aerosol) HFA-MDI
Intervention Description
E004 (Epinephrine Inhalation Aerosol) HFA-MDI, 125 mcg/inhalation, 2 inhalations QID
Intervention Type
Drug
Intervention Name(s)
Placebo-HFA
Intervention Description
Placebo-HFA, 0 mcg/inhalation, 2 inhalations QID
Primary Outcome Measure Information:
Title
Primary Efficacy Endpoint AUC of FEV1's relative change
Description
bronchodilator effect expressed as AUC of FEV1's relative change (from the same day baseline) versus time, defined as AUC of ΔFEV1%.
Time Frame
Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Secondary Outcome Measure Information:
Title
AUC of FEV1 volume changes (AUC of change in FEV1)
Description
determination of the change in FEV1 from baseline at visit to to post treatment at Visit 3
Time Frame
Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Title
Maximum of change in FEV1% (Fmax)
Description
Evaluation of maximum percent change in FEV1
Time Frame
Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Title
Curves of change in FEV1, and change in FEV1%, versus time
Description
Evaluation of curves of change in FEV1 and percent change in FEV1 over time
Time Frame
Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Title
Time to onset of bronchodilator effect (to onset), determined the time point (within 60 minutes) where FEV1 first reaches ≥12% above Same-Day Baseline.
Description
Evaluation of how much time elapses (within 60 minutes), until FEV1 first reaches ≥12% above Same-Day Baseline.
Time Frame
Study Visits 1and 3 within 60 minutes post dose
Title
The time to peak FEV1 effect (tmax), defined as the time of Fmax.
Description
Evaluation of how much time elapses until FEV1 reaches its peak
Time Frame
Study Visits 1 and 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose
Title
Duration of efficacy (duration), defined as the total length of time when ΔFEV1% reaches and stays ≥12% above Same-Day Baseline.
Description
Evaluation of the total length of time it takes until the change in FEV1% 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
Title
Percentage of positive responders (R%), including all subjects whose Fmax reaches ≥12% above Same-Day Baseline.
Description
Evaluation of what percentage of subjects are positive responders (R%), including all subjects whose Fmaxreaches ≥12% above Same-Day Baseline.
Time Frame
Study Weeks 1 and 3 within 60 minutes post dose
Title
Mean daily morning pre-dose Peak Expiratory Flow Rate (PEF)
Description
Evaluation of the mean of daily morning pre-dose Expiratory Flow Rate
Time Frame
daily pre-dose
Title
Evaluation of Vital Signs
Description
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
Time Frame
predose, and 3, 20, 60, 360 minutes post-dose
Title
12-lead ECG
Description
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
Time Frame
Pre-dose and , 3, 20 and 60 minutes post-dose (Study Visits 1 and 3)
Title
Albuterol HFA usage for rescue relief of acute asthma symptoms
Description
Evaluation Albuterol HFA usage for rescue relief of acute asthma symptoms
Time Frame
Study Visits 1, 2, and 3, within 30 min predose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
11 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Gao, M.D.
Organizational Affiliation
Amphastar Pharmaceuticals, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Amphastar Site 5
City
Costa Mesa
State/Province
California
ZIP/Postal Code
92626
Country
United States
Facility Name
Amphastar Site 8
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Amphastar Site 4
City
Stockton
State/Province
California
ZIP/Postal Code
95207
Country
United States
Facility Name
Amphastar Site 2
City
Medford
State/Province
Oregon
ZIP/Postal Code
97504
Country
United States
Facility Name
Amphastar Site 1
City
Portland
State/Province
Oregon
ZIP/Postal Code
97202
Country
United States
Facility Name
Amphastar Site 7
City
North Charleston
State/Province
South Carolina
ZIP/Postal Code
29406
Country
United States
Facility Name
Amphastar Site 3
City
El Paso
State/Province
Texas
ZIP/Postal Code
79903
Country
United States
Facility Name
Amphastar Site 6
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
2019665
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. doi: 10.1002/j.1552-4604.1991.tb04969.x.
Results Reference
background
PubMed Identifier
16400891
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. doi: 10.1016/S1081-1206(10)61014-9.
Results Reference
background
PubMed Identifier
3780129
Citation
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.
Results Reference
background
PubMed Identifier
10919679
Citation
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.
Results Reference
background
PubMed Identifier
10936150
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. doi: 10.1378/chest.118.2.522.
Results Reference
background

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Evaluation of Efficacy and Safety of E004 in Children With Asthma

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