A Study in Asthmatic Children (6 to <12 Yrs) Comparing Single Doses of Formoterol and Foradil® Evaluating Efficacy

Study Overview
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Brief Summary
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This purpose of the study is to investigate the bronchodilating effects of 3 different dosages of formoterol given in combination with budesonide as Symbicort pMDI.

Detailed Description
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A Phase 2, randomized, blinded, 5-period cross-over, placebo and active controlled, multicenter, dose-finding study comparing single doses of formoterol 2.25 µg, 4.5 µg, and 9 µg delivered via Symbicort pMDI and Foradil® 12 µg evaluating the relative bronchodilating effects and safety in children.

Official Title
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A Phase 2, Randomized, Blinded, 5-period Cross-over, Placebo and Active Controlled, Multicenter, Dose-finding Study Comparing Single Doses of Formoterol 2.25 µg, 4.5 µg, and 9 µg Delivered Via Symbicort pMDI and Foradil® 12 µg Evaluating the Relative Bronchodilating Effects and Safety in Children

Conditions
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Asthma

Intervention / Treatment
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* Drug: 80/2.25 μg Symbicort pMDI
* Drug: 80/4.5 μg Symbicort pMDI
* Drug: Foradil Aerolizer 12 μg
* Drug: 40 μg budesonide HFA pMDI
* Drug: placebo HFA pMDI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a documented clinical diagnosis of asthma for at least 6 months prior to Visit 1 Has a FEV1 measured at least 6 hours after the last dose of inhaled, short-acting β2-agonist (SABA) and at least 48 hours after the last dose of inhaled long-acting β2-agonist of =60% and =85% of predicted normal. Demonstrated reversibility of FEV1 of =15% from pre short acting beta agonist level within 15 to 30 minutes after administration of a standard dose of short acting beta agonist Exclusion Criteria: Has been hospitalized for >24 hours at least once or required emergency treatment or urgent care visit more than once for an asthma-related condition during the 6 months prior to Visit 1 Has required treatment with systemic corticosteroids (eg, oral, parenteral, or rectal) for any reason within the 12 weeks prior to Visit 1.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BUD 160/FM 2.25<br>2.25 μg formoterol (as 80/2.25 μg Symbicort pMDI × 1 inhalation) + 40 μg budesonide HFA pMDI × 2 inhalations | Drug: 80/2.25 μg Symbicort pMDI<br>* inhalation<br>Drug: 40 μg budesonide HFA pMDI<br>* inhalation<br>|
| Experimental: BUD 160/FM 4.5<br>placebo HFA pMDI × 1 inhalation + 4.5 μg formoterol (as 80/2.25 μg Symbicort pMDI × 2 inhalations) | Drug: 80/2.25 μg Symbicort pMDI<br>* inhalation<br>Drug: placebo HFA pMDI<br>* inhalation<br>|
| Experimental: BUD 160/FM 9.0<br>placebo HFA pMDI × 1 inhalation + 9 μg formoterol (as 80/4.5 μg Symbicort pMDI × 2 inhalations) | Drug: 80/4.5 μg Symbicort pMDI<br>* inhalation<br>Drug: placebo HFA pMDI<br>* inhalation<br>|
| Placebo Comparator: BUD 160<br>placebo HFA pMDI × 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations | Drug: 40 μg budesonide HFA pMDI<br>* inhalation<br>Drug: placebo HFA pMDI<br>* inhalation<br>|
| Active Comparator: BUD 160/Foradil 12.0<br>Foradil Aerolizer 12 μg × 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations | Drug: Foradil Aerolizer 12 μg<br>* inhalation<br>Drug: 40 μg budesonide HFA pMDI<br>* inhalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average 12 Hour Forced Expiratory Volume in 1 Second (FEV1) | Pulmonary function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FEV1 was obtained from the full expiratory flow-volume-time curve. FEV1 was measured at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes post administration of randomized study medication. Twelve-hour serial FEV1 was calculated through an AUC determination and then divided by time, so that the final value is expressed in liters. One subject was incorrectly administered BUD 160/ formoterol (FM) 9.0 rather than BUD 160/ Foradil 12.0 at Period 4. Hence this subject is included in the Efficacy Analysis Set, but not the Safety Analysis Set for BUD 160/ Foradil 12.0. | at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 at 12 Hours After Study Medication Inhalation | Pulmonary function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. The FEV1 value at 12 hours after dosing was taken as the 12-hour measurement (720 minutes) from the serial spirometry. One subject was incorrectly administered BUD 160/ formoterol (FM) 9.0 rather than BUD 160/ Foradil 12.0 at Period 4. Hence this subject is included in the Efficacy Analysis Set, but not the Safety Analysis Set for BUD 160/ Foradil 12.0. | 12 hours after dosing | 
| Maximal FEV1 During the 12-hour Study Period | Pulmonary function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FEV1 was measured at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes post administration of randomized study medication. The maximum FEV1 value was defined as the largest observed FEV1 value recorded during each 12-hour serial spirometry procedure. One subject was incorrectly administered BUD 160/ formoterol (FM) 9.0 rather than BUD 160/ Foradil 12.0 at Period 4. Hence this subject is included in the Efficacy Analysis Set, but not the Safety Analysis Set for BUD 160/ Foradil 12.0. | at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes postdose | 
| Urinary Excretion of Formoterol During the 12 Hours Following Inhalation of Study Drug | The amount of formoterol excreted unchanged in urine over the 12-hour period after administration [Ae(0-12h)] was calculated from the concentration of formoterol in urine multiplied by the total volume of urine collected. Volume was determined from the weight of the collected urine times an assumed urine density of 1020 g/L. The data for six patients who did not have measurable formoterol in their urine on the Foradil 12 μg treatment day was excluded from the analysis. All other urine concentrations below the lower limit of quantification were set to zero. One subject was incorrectly administered BUD 160/ formoterol (FM) 9.0 rather than BUD 160/ Foradil 12.0 at Period 4. Hence this subject is included in the Efficacy Analysis Set, but not the Safety Analysis Set for BUD 160/ Foradil 12.0. | 0 to 12 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthmatic children, Symbicort, Foradil