Evaluation of Efficacy and Safety for Single Dose of E004 in 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.
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, 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)|
- Bronchodilator effect [ Time Frame: up to 30 min pre-dose, postdose up to 3 hours ]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.
- AUC analysis [ Time Frame: up to 30 min pre-dose, postdose up to 3 hours ]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 ]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 ]Evaluation of Maximum of change in FEV1% (Fmax)
- Time response [ Time Frame: up to 30 min pre-dose, postdose up to 3 hours ]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 ]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 ]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 ]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 ]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 ]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 ]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 ]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 ]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 ]Concomitant medications will be reviewed and recorded
- Adverse Events [ Time Frame: predose and up to 3 hours postdose ]All Adverse Events/side effects will be recorded and assessed
|Study Start Date:||October 2012|
|Study Completion Date:||December 2013|
|Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
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
Single dose 0 mcg/inhalation, 2 inhalations
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01737905
|United States, California|
|West Coast Clinical Trials Global|
|Cypress, California, United States, 90630|
|United States, Oregon|
|The Clinical Research Institute of Southern Oregn, PC|
|Medford, Oregon, United States, 97504|
|Transitional Clinical Research, Inc. Allergy Associates Research Center|
|Portland, Oregon, United States, 97202|
|United States, Texas|
|Western Sky Medical|
|El Paso, Texas, United States, 79903|
|Sylvana Research Assocaites|
|San Antonio, Texas, United States, 78229|
|United States, Washington|
|ASTHMA, Inc. Clinical Research Center|
|Seattle, Washington, United States, 98115|
|Study Director:||Selina Su, MPH||Amphastar Pharmaceuticals, Inc.|