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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2013 by Amphastar Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01737905
First received: November 20, 2012
Last updated: July 9, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: Epinephrine HFA-MDI (E004)
Drug: Placebo-HFA
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Evaluation of Efficacy and Safety for Single Dose of E004 in Children With Asthma (A Randomized, Double-Blind, Placebo-Controlled, Crossover, Single Dose Study in 4 - 11 Year Old Children With Asthma)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Bronchodilator effect [ Time Frame: up to 30 min pre-dose, postdose up to 3 hours ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • AUC analysis [ Time Frame: up to 30 min pre-dose, postdose up to 3 hours ] [ Designated as safety issue: No ]
    The comparative analysis of AUC of FEV1 versus time

  • Evaluation of FEV1 volume changes [ Time Frame: up to 30 min pre-dose, postdose up to 3 hours ] [ Designated as safety issue: No ]
    Evaluation of AUC(0-3) and AUC(0-4) of FEV1 volume changes (AUC of ΔFEV1)

  • Change in FEV1 [ Time Frame: up to 30 min pre-dose, postdose up to 3 hours ] [ Designated as safety issue: No ]
    Evaluation of Maximum of change in FEV1% (Fmax)

  • Time response [ Time Frame: up to 30 min pre-dose, postdose up to 3 hours ] [ Designated as safety issue: No ]
    Evaluation of time response curves of change in FEV1 and FEV1%

  • Time to onset of bronchodilator effect [ Time Frame: up to 30 min pre-dose, postdose up to 3 hours ] [ Designated as safety issue: No ]
    Determination of time to onset of bronchodilator effect (Tonset), determined by the time point (within 60 minutes) where FEV1 first reaches greater than or equal to 12% above Same-Day Pre-dose Baseline

  • Time to peak FEV1 effect [ Time Frame: up to 30 min pre-dose, postdose up to 3 hours ] [ Designated as safety issue: No ]
    The time to peak FEV1 effect (Tmax), defined as the time of Fmax

  • Duration of efficacy [ Time Frame: up to 30 min pre-dose, postdose up to 3 hours ] [ Designated as safety issue: No ]
    Evaluation of duration of efficacy (Tduration), defined as the total length of time when the change in FEV1% reaches and stays greater than or equal to 12% above Same-Day Pre-dose Baseline

  • Percentage of positive responders [ Time Frame: up to 30 min pre-dose, postdose up to 3 hours ] [ Designated as safety issue: No ]
    Evaluation of percentage of positive responders (R%), including all subjects whose Fmax reaches more than or equal to 12% above Same-Day Pre-dose Baseline

  • Vital Signs [ Time Frame: Screening Visit: baseline up to 30 min predose and 30 min post dose; Visits 1-2: Baseline upt o 30 min predose and 3, 20, 60, and 240 min post-dose ] [ Designated as safety issue: Yes ]
    Vital signs (SBP/DBP, and heart rate) will be monitored at the Screening Visit and at Study Visits 1 and 2

  • 12-lead ECG (Routine and QT/QTc) [ Time Frame: Screening Visit: baseline up to 30 min predose and 30 min post dose; Visits 1-2: Baseline upt o 30 min predose and 3, 20, and 60 min post-dose ] [ Designated as safety issue: Yes ]
    A 12-lead ECG (Routine and QT/QTc) will be recorded at Screening Visit and at the Study Visits 1 and 2

  • Lab Tests [ Time Frame: prior to first dose ] [ Designated as safety issue: Yes ]
    Lab tests for CBC, blood chemistry panel (8-hr fasted), and urinalysis will be performed at screening

  • Albuterol HFA Usage [ Time Frame: up to 30 min predose ] [ Designated as safety issue: Yes ]
    Albuterol HFA usage for rescue relief of acute asthma symptoms will be recorded at each visit

  • Concomitant Medications [ Time Frame: up to 30 min predose ] [ Designated as safety issue: Yes ]
    Concomitant medications will be reviewed and recorded

  • Adverse Events [ Time Frame: predose and up to 3 hours postdose ] [ Designated as safety issue: Yes ]
    All Adverse Events/side effects will be recorded and assessed


Estimated Enrollment: 24
Study Start Date: November 2013
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm T
Experimental arm utilizing Epinephrine HFA-MDI (E004)
Drug: Epinephrine HFA-MDI (E004)
Single dose 125 mcg/inhalation, 2 inhalations
Placebo Comparator: Arm P
Placebo comparator arm utilizing Placebo-HFA
Drug: Placebo-HFA
Single dose 0 mcg/inhalation, 2 inhalations

Detailed Description:

This is a randomized, double-blinded, placebo-controlled, crossover, single dose study to be conducted in pediatric patients (4 - 11 years) with asthma.

The main features of the study design are:

The entire study consists of a Screening Visit, and a Study Period consisting of two (2) crossover Study Visits separated by a 2 to 14-day interval. All study subjects must be properly consented, under adult supervision, and screened against the inclusion and exclusion criteria at the Screening Visit and confirmed for enrollment on Visit 1. Efficacy and safety evaluations of E004 are conducted at each Study Visit.

This study employs two (2) double-blinded treatment arms as outlined in Table 2. A double-blinded design will be applied to E004 (Arm T) and Placebo-HFA (Arm P) since they are identical in all physical attributes and share a comparable formulation.

The enrolled subjects will be randomized into two sequences (as follows) to participate in two (2) crossover Study Visits with a 2 - 14 day interval between visits. Randomization is achieved using a ratio of 1:1.

Use E004 (T) and Placebo (P) in Visits 1 and 2, respectively or use Placebo (P) and E004 (T) in Visits 1 and 2, respectively

Subjects will be trained at the screening visit and each Study Visit for the correct dosing and spirometry methods. Under the supervision of dosing monitor, subjects will self-administer two (2) inhalations of the randomized study treatment, with a ~1 min interval at each Study Visit.

For the Screening and Study Visits, the subjects will be required to be at the site for a 30 minute "resting period". This resting period is designed to maintain a stable and consistent physical status of the subjects prior to the start of the baseline FEV1 procedures. For the Screening Visit, this period will begin upon subject arrival. For the Study Visits, the period will begin at the end of the option breakfast (or upon arrival if the breakfast is declined).

For each Study Visit, subjects will need to arrive at the study site early enough to complete all necessary baseline evaluations. The study site will provide an optional breakfast but it must be eaten at least 30 minutes prior to the pre-dose baseline FEV1 measurements. The optional breakfast will be light, and contain no added sugar. If the subjects decline the breakfast (i.e. they have already eaten a light breakfast prior to arriving), they are required to remain at the site for at least 30 minutes prior to the start of the Baseline FEV1 measurements, in order to maintain a stable physical status.

Baseline vital signs and safety evaluations will be taken prior to the pre-dose baseline FEV1 measurement. These can be performed during the 30 minute "resting period". Efficacy of the treatments at each visit will be evaluated based on spirometric measurements of serial FEV1 determined at the Pre-dose Baseline, and the seven (7) serial Post-dose FEV1 responses at 5, 30, 60, 120, 150, 180) and 240 minutes.

This study will be conducted with a double-blinded technique. This means neither the subject nor the site staff will be aware of the identity of the treatment arm since both study treatments are in identical looking containers.

  Eligibility

Ages Eligible for Study:   4 Years to 11 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  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: NCT01737905

Contacts
Contact: Selina Su, MPH (626) 459-5523 selinas@amphastar.com

Locations
United States, California
West Coast Clinical Trials Global Not yet recruiting
Cypress, California, United States, 90630
Contact: Selina Su, MPH    626-459-5523 ext 2030    selinas@ims-limited.com   
Principal Investigator: Anoshie Ratnayake, M.D.         
United States, Oregon
The Clinical Research Institute of Southern Oregn, PC Not yet recruiting
Medford, Oregon, United States, 97504
Contact: Selina Su, MPH    626-459-5523    selinas@amphastar.com   
Principal Investigator: Edward M Kerwin, M.D.         
Transitional Clinical Research, Inc. Allergy Associates Research Center Not yet recruiting
Portland, Oregon, United States, 97202
Contact: Selina Su, MPH    626-459-5523    selinas@ims-limited.com   
Principal Investigator: Anothony Montanaro, M.D.         
United States, Texas
Western Sky Medical Not yet recruiting
El Paso, Texas, United States, 79903
Contact: Selina Su, MPH    626-459-5523 ext 2030    selinas@ims-limited.com   
Principal Investigator: Lyndon E Mansfield, M.D.         
Sylvana Research Assocaites Not yet recruiting
San Antonio, Texas, United States, 78229
Contact: Selina Su, MPH    626-459-5523    selinas@ims-limited.com   
Principal Investigator: Paul Ratner, M.D.         
United States, Washington
ASTHMA, Inc. Clinical Research Center Not yet recruiting
Seattle, Washington, United States, 98115
Contact: Selina Su, MPH    626-459-5523    selinas@ims-limited.com   
Principal Investigator: Stephen Tilles, M.D.         
Sponsors and Collaborators
Amphastar Pharmaceuticals, Inc.
Investigators
Study Director: Selina Su, MPH Amphastar Pharmaceuticals, Inc.
  More Information

Publications:
Responsible Party: Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01737905     History of Changes
Other Study ID Numbers: API-E004-CL-D2
Study First Received: November 20, 2012
Last Updated: July 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Amphastar Pharmaceuticals, Inc.:
Asthma
Safety
Efficacy
Epinephrine
Bronchodilator
Metered dose inhaler

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 24, 2014