Evaluation of Efficacy and Safety of E004 in Children With Asthma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01460511
First received: October 24, 2011
Last updated: July 11, 2012
Last verified: July 2012
  Purpose

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 Intervention Phase
Asthma
Drug: Epinephrine Inhalation Aerosol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Amphastar Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Visit 1 and Visit 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose ] [ Designated as safety issue: No ]
    determination of the change in FEV1 from baseline at visit to to post treatment at Visit 3

  • 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 ] [ Designated as safety issue: No ]
    Evaluation of maximum percent change in FEV1

  • 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 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Study Visits 1and 3 within 60 minutes post dose ] [ Designated as safety issue: No ]
    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. [ Time Frame: Study Visits 1 and 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose ] [ Designated as safety issue: No ]
    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. [ Time Frame: Study Weeks 1and 3 at 5, 30, 60, 120, 180, 240, and 360 minutes post-dose ] [ Designated as safety issue: No ]
    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. [ Time Frame: Study Weeks 1 and 3 within 60 minutes post dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: daily pre-dose ] [ Designated as safety issue: No ]
    Evaluation of the mean of daily morning pre-dose Expiratory Flow Rate

  • Evaluation of Vital Signs [ Time Frame: predose, and 3, 20, 60, 360 minutes post-dose ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Pre-dose and , 3, 20 and 60 minutes post-dose (Study Visits 1 and 3) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Study Visits 1, 2, and 3, within 30 min predose ] [ Designated as safety issue: Yes ]
    Evaluation Albuterol HFA usage for rescue relief of acute asthma symptoms


Enrollment: 70
Study Start Date: October 2011
Study Completion Date: July 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   4 Years to 11 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01460511

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

Publications:
Responsible Party: Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01460511     History of Changes
Other Study ID Numbers: API-E004-CL-D
Study First Received: October 24, 2011
Last Updated: July 11, 2012
Health Authority: United States: Food and Drug Administration

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
Epinephryl borate
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Mydriatics
Adrenergic alpha-Agonists
Sympathomimetics
Vasoconstrictor Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on July 26, 2014