Trial Outcomes & Findings for A Study in Asthmatic Children (6 to <12 Yrs) Comparing Single Doses of Formoterol and Foradil® Evaluating Efficacy (NCT NCT01136655)

Last Updated: 2013-10-31

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

54 participants

Primary outcome timeframe

at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes postdose

Results posted on

2013-10-31

Participant Flow

This multicenter study was conducted in Europe and the United States between 7 October 2010 and 3 January 2012.

The study consisted of a screening visit, an enrolment visit, a 1- to 2-week run-in (standardization) period, randomization at Visit 3, and 4 further visits (Visits 4-7)separated by approximately 7-day (minimum 3 days; maximum 14 days) wash-out (stabilization) periods. Subjects received 1 of 5 single-dose treatments at Visits 3-7, in random order.

Participant milestones

Participant milestones
Measure	Randomized Patients All randomized patients
BUD 160/FM 2.25 (1 Dose) STARTED	54
BUD 160/FM 2.25 (1 Dose) COMPLETED	54
BUD 160/FM 2.25 (1 Dose) NOT COMPLETED	0
Washout After BUD 160/FM 2.25 (7 Days) STARTED	54
Washout After BUD 160/FM 2.25 (7 Days) COMPLETED	53
Washout After BUD 160/FM 2.25 (7 Days) NOT COMPLETED	1
BUD 160/FM 4.5 (1 Dose) STARTED	53
BUD 160/FM 4.5 (1 Dose) COMPLETED	53
BUD 160/FM 4.5 (1 Dose) NOT COMPLETED	0
Washout After BUD 160/FM 4.5 (7 Days) STARTED	53
Washout After BUD 160/FM 4.5 (7 Days) COMPLETED	52
Washout After BUD 160/FM 4.5 (7 Days) NOT COMPLETED	1
BUD 160/FM 9.0 (1 Dose) STARTED	53
BUD 160/FM 9.0 (1 Dose) COMPLETED	53
BUD 160/FM 9.0 (1 Dose) NOT COMPLETED	0
Washout After BUD 160/FM 9.0 (7 Days) STARTED	53
Washout After BUD 160/FM 9.0 (7 Days) COMPLETED	51
Washout After BUD 160/FM 9.0 (7 Days) NOT COMPLETED	2
BUD 160 (1 Dose) STARTED	51
BUD 160 (1 Dose) COMPLETED	51
BUD 160 (1 Dose) NOT COMPLETED	0
Washout After BUD 160 (7 Days) STARTED	51
Washout After BUD 160 (7 Days) COMPLETED	51
Washout After BUD 160 (7 Days) NOT COMPLETED	0
BUD 160/ Foradil 12.0 (1 Dose) STARTED	50
BUD 160/ Foradil 12.0 (1 Dose) COMPLETED	50
BUD 160/ Foradil 12.0 (1 Dose) NOT COMPLETED	0
Washout After BUD 160/ Foradil (7 Days) STARTED	50
Washout After BUD 160/ Foradil (7 Days) COMPLETED	50
Washout After BUD 160/ Foradil (7 Days) NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Randomized Patients All randomized patients
Washout After BUD 160/FM 2.25 (7 Days) Withdrawal by Subject	1
Washout After BUD 160/FM 4.5 (7 Days) Adverse Event	1
Washout After BUD 160/FM 9.0 (7 Days) Withdrawal by Subject	1
Washout After BUD 160/FM 9.0 (7 Days) Adverse Event	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Randomized Patients n=54 Participants All randomized patients
Age Continuous	9.2 years STANDARD_DEVIATION 1.79 • n=93 Participants
Age, Customized >=6 to <8 years	11 participants n=93 Participants
Age, Customized >=8 to < 12 years	43 participants n=93 Participants
Sex: Female, Male Female	23 Participants n=93 Participants
Sex: Female, Male Male	31 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	22 Participants n=93 Participants
Race (NIH/OMB) White	31 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants

PRIMARY outcome

Timeframe: at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes postdose

Population: Efficacy analysis set including all patients who were randomized (defined as having a randomization code recorded on the demography case report form), received at least one dose of study medication, and contributed sufficient data for at least one efficacy endpoint.

Outcome measures

Outcome measures
Measure	BUD 160/FM 2.25 n=54 Participants 2.25 μg formoterol (as 80/2.25 μg Symbicort pMDI x 1 inhalation) + 40 μg budesonide HFA pMDI × 2 inhalations	BUD 160/FM 4.5 n=53 Participants placebo HFA pMDI x 1 inhalation + 4.5 μg formoterol (as 80/2.25 μg Symbicort pMDI x 2 inhalations)	BUD 160/FM 9.0 n=53 Participants placebo HFA pMDI x 1 inhalation + 9 μg formoterol (as 80/4.5 μg Symbicort pMDI x 2 inhalations)	BUD 160 n=51 Participants placebo HFA pMDI x 1 inhalation + 80 μg budesonide HFA pMDI x 2 inhalations	BUD 160/ Foradil 12.0 n=51 Participants Foradil Aerolizer 12 μg x 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations
Average 12 Hour Forced Expiratory Volume in 1 Second (FEV1)	1.546 liters Standard Error 0.0097	1.594 liters Standard Error 0.0099	1.603 liters Standard Error 0.0099	1.489 liters Standard Error 0.0101	1.603 liters Standard Error 0.0101

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	BUD 160/FM 2.25 n=54 Participants 2.25 μg formoterol (as 80/2.25 μg Symbicort pMDI x 1 inhalation) + 40 μg budesonide HFA pMDI × 2 inhalations	BUD 160/FM 4.5 n=53 Participants placebo HFA pMDI x 1 inhalation + 4.5 μg formoterol (as 80/2.25 μg Symbicort pMDI x 2 inhalations)	BUD 160/FM 9.0 n=53 Participants placebo HFA pMDI x 1 inhalation + 9 μg formoterol (as 80/4.5 μg Symbicort pMDI x 2 inhalations)	BUD 160 n=51 Participants placebo HFA pMDI x 1 inhalation + 80 μg budesonide HFA pMDI x 2 inhalations	BUD 160/ Foradil 12.0 n=51 Participants Foradil Aerolizer 12 μg x 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations
FEV1 at 12 Hours After Study Medication Inhalation	1.641 liters Standard Error 0.0175	1.692 liters Standard Error 0.0177	1.731 liters Standard Error 0.0177	1.626 liters Standard Error 0.0181	1.709 liters Standard Error 0.0182

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	BUD 160/FM 2.25 n=54 Participants 2.25 μg formoterol (as 80/2.25 μg Symbicort pMDI x 1 inhalation) + 40 μg budesonide HFA pMDI × 2 inhalations	BUD 160/FM 4.5 n=53 Participants placebo HFA pMDI x 1 inhalation + 4.5 μg formoterol (as 80/2.25 μg Symbicort pMDI x 2 inhalations)	BUD 160/FM 9.0 n=53 Participants placebo HFA pMDI x 1 inhalation + 9 μg formoterol (as 80/4.5 μg Symbicort pMDI x 2 inhalations)	BUD 160 n=51 Participants placebo HFA pMDI x 1 inhalation + 80 μg budesonide HFA pMDI x 2 inhalations	BUD 160/ Foradil 12.0 n=51 Participants Foradil Aerolizer 12 μg x 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations
Maximal FEV1 During the 12-hour Study Period	1.833 liters Standard Error 0.0119	1.889 liters Standard Error 0.0120	1.884 liters Standard Error 0.0120	1.777 liters Standard Error 0.0123	1.892 liters Standard Error 0.0123

SECONDARY outcome

Timeframe: 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.