Clinical trial NCT01737905: Evaluation of Efficacy and Safety for Single Dose of E004 in Children With Asthma
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
Safety
Efficacy
Epinephrine
Bronchodilator
Metered dose inhaler
Lead sponsor: Amphastar Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2012-11-30
Enrollment: 28
Sex: ALL
Minimum age (years): 4
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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. All study subjects must be properly consented, under adult supervision, and screened against the inclusion and exclusion criteria, at the Screening Visit.

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 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.

Primary outcomes:
measure: Bronchodilator effect
timeFrame: up to 30 min pre-dose, postdose up to 3 hours
Secondary outcomes:
measure: AUC analysis
timeFrame: up to 30 min pre-dose, postdose up to 3 hours
measure: Evaluation of FEV1 volume changes
timeFrame: up to 30 min pre-dose, postdose up to 3 hours
measure: Change in FEV1
timeFrame: up to 30 min pre-dose, postdose up to 3 hours
measure: Time response
timeFrame: up to 30 min pre-dose, postdose up to 3 hours
measure: Time to onset of bronchodilator effect
timeFrame: up to 30 min pre-dose, postdose up to 3 hours
measure: Time to peak FEV1 effect
timeFrame: up to 30 min pre-dose, postdose up to 3 hours
measure: Duration of efficacy
timeFrame: up to 30 min pre-dose, postdose up to 3 hours
measure: Percentage of positive responders
timeFrame: up to 30 min pre-dose, postdose up to 3 hours
measure: Vital Signs
timeFrame: 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
measure: 12-lead ECG (Routine and QT/QTc)
timeFrame: 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
measure: Lab Tests
timeFrame: prior to first dose
measure: Albuterol HFA Usage
timeFrame: up to 30 min predose
measure: Concomitant Medications
timeFrame: up to 30 min predose
measure: Adverse Events
timeFrame: predose and up to 3 hours postdose
Other outcomes:
Locations:
city: Cypress
country: United States
facility: West Coast Clinical Trials Global
state: California
city: Medford
country: United States
facility: The Clinical Research Institute of Southern Oregn, PC
state: Oregon
city: Portland
country: United States
facility: Transitional Clinical Research, Inc. Allergy Associates Research Center
state: Oregon
city: El Paso
country: United States
facility: Western Sky Medical
state: Texas
city: San Antonio
country: United States
facility: Sylvana Research Assocaites
state: Texas
city: Seattle
country: United States
facility: ASTHMA, Inc. Clinical Research Center
state: Washington
Study officials:
affiliation: Amphastar Pharmaceuticals, Inc.
name: Selina Su, MPH
role: STUDY_DIRECTOR
References:
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