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AsthmaPhase 3NCT01737905

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

A Phase 3 study testing Epinephrine HFA-MDI (E004) in people with Asthma, run by Amphastar Pharmaceuticals, Inc. at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 4 to 11 yearsHealthy volunteers can take part
Conditions the study is for
Asthma
What is being tested?
Epinephrine HFA-MDI (E004)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
28 participants
Where
6 sitesUnited States
Study dates
Oct 2012to Dec 2013
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 to 11 years
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites
  • West Coast Clinical Trials Global

    Cypress, California, 90630

  • Western Sky Medical

    El Paso, Texas, 79903

  • The Clinical Research Institute of Southern Oregn, PC

    Medford, Oregon, 97504

  • Transitional Clinical Research, Inc. Allergy Associates Research Center

    Portland, Oregon, 97202

  • Sylvana Research Assocaites

    San Antonio, Texas, 78229

  • ASTHMA, Inc. Clinical Research Center

    Seattle, Washington, 98115

Other trials in United States

About this study

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)

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.

Read the 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.

Conditions
Asthma
Being tested
Epinephrine HFA-MDI (E004), Placebo-HFA
Keywords
Asthma, Safety, Efficacy, Epinephrine, Bronchodilator, Metered dose inhaler
Medical subject headings
Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Epinephrine HFA-MDI (E004)Drug

    Single dose 125 mcg/inhalation, 2 inhalations

  • Placebo-HFADrug

    Single dose 0 mcg/inhalation, 2 inhalations

Study groups in NCT01737905
Study groupRoleWhat they receive
Arm TExperimentalExperimental arm utilizing Epinephrine HFA-MDI (E004)
Receives: Drug: Epinephrine HFA-MDI (E004)
Arm PPlacebo comparatorPlacebo comparator arm utilizing Placebo-HFA
Receives: Drug: Placebo-HFA

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Bronchodilator effect

    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.

    Measured: up to 30 min pre-dose, postdose up to 3 hours

Secondary outcomes (14)
  1. AUC analysis

    The comparative analysis of AUC of FEV1 versus time

    Measured: up to 30 min pre-dose, postdose up to 3 hours

  2. Evaluation of FEV1 volume changes

    Evaluation of AUC(0-3) and AUC(0-4) of FEV1 volume changes (AUC of ΔFEV1)

    Measured: up to 30 min pre-dose, postdose up to 3 hours

  3. Change in FEV1

    Evaluation of Maximum of change in FEV1% (Fmax)

    Measured: up to 30 min pre-dose, postdose up to 3 hours

  4. Time response

    Evaluation of time response curves of change in FEV1 and FEV1%

    Measured: up to 30 min pre-dose, postdose up to 3 hours

  5. Time to onset of bronchodilator effect

    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

    Measured: up to 30 min pre-dose, postdose up to 3 hours

  6. Time to peak FEV1 effect

    The time to peak FEV1 effect (Tmax), defined as the time of Fmax

    Measured: up to 30 min pre-dose, postdose up to 3 hours

  7. Duration of efficacy

    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

    Measured: up to 30 min pre-dose, postdose up to 3 hours

  8. Percentage of positive responders

    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

    Measured: up to 30 min pre-dose, postdose up to 3 hours

  9. Vital Signs

    Vital signs (SBP/DBP, and heart rate) will be monitored at the Screening Visit and at Study Visits 1 and 2

    Measured: 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

  10. 12-lead ECG (Routine and QT/QTc)

    A 12-lead ECG (Routine and QT/QTc) will be recorded at Screening Visit and at the Study Visits 1 and 2

    Measured: 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

  11. Lab Tests

    Lab tests for CBC, blood chemistry panel (8-hr fasted), and urinalysis will be performed at screening

    Measured: prior to first dose

  12. Albuterol HFA Usage

    Albuterol HFA usage for rescue relief of acute asthma symptoms will be recorded at each visit

    Measured: up to 30 min predose

  13. Concomitant Medications

    Concomitant medications will be reviewed and recorded

    Measured: up to 30 min predose

  14. Adverse Events

    All Adverse Events/side effects will be recorded and assessed

    Measured: predose and up to 3 hours postdose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Nov 2012 (estimated)
  2. Study startOct 2012
  3. Primary completionMar 2013
  4. Study completionDec 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01737905
Sponsor's protocol ID
API-E004-CL-D2
Status last verified
Feb 2016
First submitted
20 Nov 2012
Last updated
11 Mar 2016
Results posted
No
Data monitoring committee
No

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. doi: 10.1002/j.1552-4604.1991.tb04969.x.

    PubMed 2019665
  • 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.

    PubMed 16400891
  • 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.

    PubMed 3780129
  • 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.

    PubMed 10919679
  • 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.

    PubMed 10936150
  • Simons FE, Gu X, Johnston LM, Simons KJ. Can epinephrine inhalations be substituted for epinephrine injection in children at risk for systemic anaphylaxis? Pediatrics. 2000 Nov;106(5):1040-4. doi: 10.1542/peds.106.5.1040.

    PubMed 11061773
  • Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999 Jan;159(1):179-87. doi: 10.1164/ajrccm.159.1.9712108.

    PubMed 9872837

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Epinephrine HFA-MDI (E004) in people with Asthma, run by Amphastar Pharmaceuticals, Inc. at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Bronchodilator effect (time frame: up to 30 min pre-dose, postdose up to 3 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01737905, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2016.

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