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

Phase 2

Completed

Conditions: Asthma

Interventions: 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

Registration Number: NCT01136655

Lead Sponsor: AstraZeneca

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 54

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
BUD 160/FM 2.25	80/2.25 μg Symbicort pMDI	2.25 μg formoterol (as 80/2.25 μg Symbicort pMDI × 1 inhalation) + 40 μg budesonide HFA pMDI × 2 inhalations
BUD 160/FM 2.25	40 μg budesonide HFA pMDI	2.25 μg formoterol (as 80/2.25 μg Symbicort pMDI × 1 inhalation) + 40 μg budesonide HFA pMDI × 2 inhalations
BUD 160/FM 4.5	80/2.25 μg Symbicort pMDI	placebo HFA pMDI × 1 inhalation + 4.5 μg formoterol (as 80/2.25 μg Symbicort pMDI × 2 inhalations)
BUD 160/FM 4.5	placebo HFA pMDI	placebo HFA pMDI × 1 inhalation + 4.5 μg formoterol (as 80/2.25 μg Symbicort pMDI × 2 inhalations)
BUD 160/FM 9.0	80/4.5 μg Symbicort pMDI	placebo HFA pMDI × 1 inhalation + 9 μg formoterol (as 80/4.5 μg Symbicort pMDI × 2 inhalations)
BUD 160	placebo HFA pMDI	placebo HFA pMDI × 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations
BUD 160/Foradil 12.0	Foradil Aerolizer 12 μg	Foradil Aerolizer 12 μg × 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations
BUD 160/FM 9.0	placebo HFA pMDI	placebo HFA pMDI × 1 inhalation + 9 μg formoterol (as 80/4.5 μg Symbicort pMDI × 2 inhalations)
BUD 160	40 μg budesonide HFA pMDI	placebo HFA pMDI × 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations
BUD 160/Foradil 12.0	40 μg budesonide HFA pMDI	Foradil Aerolizer 12 μg × 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations

Primary Outcome Measures

Name	Time	Method
Average 12 Hour Forced Expiratory Volume in 1 Second (FEV1)	at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes postdose	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.

Secondary Outcome Measures

Name	Time	Method
Maximal FEV1 During the 12-hour Study Period	at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes postdose	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.
FEV1 at 12 Hours After Study Medication Inhalation	12 hours after dosing	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.
Urinary Excretion of Formoterol During the 12 Hours Following Inhalation of Study Drug	0 to 12 hours	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.