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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BUD 160/FM 2.25 | Experimental | 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 | Experimental | placebo HFA pMDI × 1 inhalation + 4.5 μg formoterol (as 80/2.25 μg Symbicort pMDI × 2 inhalations) |
|
| BUD 160/FM 9.0 | Experimental | placebo HFA pMDI × 1 inhalation + 9 μg formoterol (as 80/4.5 μg Symbicort pMDI × 2 inhalations) |
|
| BUD 160 | Placebo Comparator | placebo HFA pMDI × 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations |
|
| BUD 160/Foradil 12.0 | Active Comparator | Foradil Aerolizer 12 μg × 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 80/2.25 μg Symbicort pMDI | Drug | inhalation |
| |
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lars-Goran Carlsson, MD | AstraZeneca | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Huntington | California | United States | |||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24717790 | Derived | Berger WE, Gillen M, Eckerwall G, Uryniak T, Trudo FJ, Lampl KL. Bronchodilator effect of single-dose formoterol administered by pressurized metered-dose inhaler in children with asthma aged 6 to <12 years receiving budesonide. Allergy Asthma Proc. 2014 Mar-Apr;35(2):134-40. doi: 10.2500/aap.2014.35.3746. |
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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.
This multicenter study was conducted in Europe and the United States between 7 October 2010 and 3 January 2012.
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| ID | Title | Description |
|---|---|---|
| FG000 | Randomized Patients | All randomized patients |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| BUD 160/FM 2.25 (1 Dose) |
|
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| 80/4.5 μg Symbicort pMDI |
| Drug |
inhalation |
|
| Foradil Aerolizer 12 μg | Drug | inhalation |
|
| 40 μg budesonide HFA pMDI | Drug | inhalation |
|
| placebo HFA pMDI | Drug | inhalation |
|
| 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 |
| Long Beach |
| California |
| United States |
| Research Site | Mission Viejo | California | United States |
| Research Site | Orange | California | United States |
| Research Site | Rolling Hills Estate | California | United States |
| Research Site | Sarasota | Florida | United States |
| Research Site | Omaha | Nebraska | United States |
| Research Site | Morrisville | North Carolina | United States |
| Research Site | Raleigh | North Carolina | United States |
| Research Site | Eugene | Oregon | United States |
| Research Site | Lake Oswego | Oregon | United States |
| Research Site | Medford | Oregon | United States |
| Research Site | Portland | Oregon | United States |
| Research Site | Altoona | Pennsylvania | United States |
| Research Site | Upland | Pennsylvania | United States |
| Research Site | Charleston | South Carolina | United States |
| Research Site | El Paso | Texas | United States |
| Research Site | San Antonio | Texas | United States |
| Research Site | Waco | Texas | United States |
| Research Site | Springfield | Virginia | United States |
| Research Site | Dublin | Bulgaria |
| Research Site | Dublin | Czechia |
| Research Site | Budapest | Hungary |
| Research Site | Dublin | Hungary |
| Research Site | Miskolc | Hungary |
| Research Site | Sopron | Hungary |
| Research Site | Dublin | Poland |
| Research Site | Krugersdorp | Gauteng | South Africa |
| Research Site | Pietermariztburg | KwaZulu-Natal | South Africa |
| Research Site | Durban | Kz-natal | South Africa |
| Research Site | Cape Town | South Africa | South Africa |
| Research Site | Cape Town | W Cape | South Africa |
| Research Site | Claremont | W Cape | South Africa |
| Research Site | Dublin | South Africa |
| COMPLETED |
|
| NOT COMPLETED |
|
| Washout After BUD 160/FM 2.25 (7 Days) |
|
|
| BUD 160/FM 4.5 (1 Dose) |
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| Washout After BUD 160/FM 4.5 (7 Days) |
|
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| BUD 160/FM 9.0 (1 Dose) |
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| Washout After BUD 160/FM 9.0 (7 Days) |
|
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| BUD 160 (1 Dose) |
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| Washout After BUD 160 (7 Days) |
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| BUD 160/ Foradil 12.0 (1 Dose) |
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| Washout After BUD 160/ Foradil (7 Days) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Randomized Patients | All randomized patients |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Age, Customized | Number | participants |
| |||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Least Squares Mean | Standard Error | liters | at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes postdose |
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| Secondary | 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. | 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. | Posted | Least Squares Mean | Standard Error | liters | 12 hours after dosing |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | 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. | Posted | Least Squares Mean | Standard Error | liters | at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes postdose |
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| Secondary | 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | pmol | 0 to 12 hours |
|
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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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BUD 160/FM 2.25 | 2.25 μg formoterol (as 80/2.25 μg Symbicort pMDI x 1 inhalation) + 40 μg budesonide HFA pMDI × 2 inhalations | 0 | 54 | 1 | 54 | ||
| EG001 | BUD 160/FM 4.5 | placebo HFA pMDI x 1 inhalation + 4.5 μg formoterol (as 80/2.25 μg Symbicort pMDI x 2 inhalations) | 0 | 53 | 1 | 53 | ||
| EG002 | BUD 160/FM 9.0 | placebo HFA pMDI x 1 inhalation + 9 μg formoterol (as 80/4.5 μg Symbicort pMDI x 2 inhalations) | 0 | 53 | 5 | 53 | ||
| EG003 | BUD 160 | placebo HFA pMDI x 1 inhalation + 80 μg budesonide HFA pMDI x 2 inhalations | 0 | 51 | 2 | 51 | ||
| EG004 | BUD 160/ Foradil 12.0 | Foradil Aerolizer 12 μg x 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations | 0 | 50 | 0 | 50 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Göran Eckerwall, MSD | AstraZeneca | ClinicalTrialTransparency@astrazeneca.com |
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000068759 | Formoterol Fumarate |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
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| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
Factors in the ANCOVA model included: patient, visit, treatment, and the covariate pre-dose FEV1 from each visit. |
| ANCOVA |
LOCF was performed if missing data were post last non-missing post-baseline assessment. |
| <0.0001 |
| LS mean difference |
| 0.105 |
| Standard Error of the Mean |
| 0.0140 |
| 2-Sided |
| 95 |
| 0.078 |
| 0.133 |
| No |
| Superiority or Other |
| Factors in the ANCOVA model included: patient, visit, treatment, and the covariate pre-dose FEV1 from each visit. | ANCOVA | LOCF was performed if missing data were post last non-missing post-baseline assessment. | 0.0001 | LS mean difference | 0.058 | Standard Error of the Mean | 0.0141 | 2-Sided | 95 | 0.030 | 0.085 | No | Superiority or Other |
| Factors in the ANCOVA model included: patient, visit, treatment, and the covariate pre-dose FEV1 from each visit. | ANCOVA | LOCF was performed if missing data were post last non-missing post-baseline assessment. | 0.5223 | LS mean difference | -0.009 | Standard Error of the Mean | 0.0139 | 2-Sided | 95 | -0.036 | 0.018 | No | Superiority or Other |
| Factors in the ANCOVA model included: patient, visit, treatment, and the covariate pre-dose FEV1 from each visit. | ANCOVA | LOCF was performed if missing data were post last non-missing post-baseline assessment. | 0.0001 | LS mean difference | -0.057 | Standard Error of the Mean | 0.0139 | 2-Sided | 95 | -0.084 | -0.029 | No | Superiority or Other |
| Factors in the ANCOVA model included: patient, visit, treatment, and the covariate pre-dose FEV1 from each visit. | ANCOVA | LOCF was performed if missing data were post last non-missing post-baseline assessment. | 0.0007 | LS mean difference | -0.048 | Standard Error of the Mean | 0.0138 | 2-Sided | 95 | -0.075 | -0.020 | No | Superiority or Other |
| Factors in the ANCOVA model included: patient, visit, treatment, and the covariate pre-dose FEV1 from each visit. | ANCOVA | LOCF was performed if missing data were post last non-missing post-baseline assessment. | <0.0001 | LS mean difference | -0.114 | Standard Error of the Mean | 0.0141 | 2-Sided | 95 | -0.142 | -0.086 | No | Superiority or Other |
| Factors in the ANCOVA model included: patient, visit, treatment, and the covariate pre-dose FEV1 from each visit. | ANCOVA | LOCF was performed if missing data were post last non-missing post-baseline assessment. | 0.0001 | LS mean difference | -0.056 | Standard Error of the Mean | 0.0141 | 2-Sided | 95 | -0.084 | -0.028 | No | Superiority or Other |
| Factors in the ANCOVA model included: patient, visit, treatment, and the covariate pre-dose FEV1 from each visit. | ANCOVA | LOCF was performed if missing data were post last non-missing post-baseline assessment. | 0.5394 | LS mean difference | -0.009 | Standard Error of the Mean | 0.0141 | 2-Sided | 95 | -0.036 | 0.019 | No | Superiority or Other |
| Factors in the ANCOVA model included: patient, visit, treatment, and the covariate pre-dose FEV1 from each visit. | ANCOVA | LOCF was performed if missing data were post last non-missing post-baseline assessment. | 0.9863 | LS mean difference | 0.000 | Standard Error of the Mean | 0.0140 | 2-Sided | 95 | -0.027 | 0.028 | No | Superiority or Other |
placebo HFA pMDI x 1 inhalation + 9 μg formoterol (as 80/4.5 μg Symbicort pMDI x 2 inhalations)
| OG003 | BUD 160 | placebo HFA pMDI x 1 inhalation + 80 μg budesonide HFA pMDI x 2 inhalations |
| OG004 | BUD 160/ Foradil 12.0 | Foradil Aerolizer 12 μg x 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations |
|
|
|
| OG002 |
| BUD 160/FM 9.0 |
placebo HFA pMDI x 1 inhalation + 9 μg formoterol (as 80/4.5 μg Symbicort pMDI x 2 inhalations) |
| OG003 | BUD 160 | placebo HFA pMDI x 1 inhalation + 80 μg budesonide HFA pMDI x 2 inhalations |
| OG004 | BUD 160/ Foradil 12.0 | Foradil Aerolizer 12 μg x 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations |
|
|
|
| OG002 | BUD 160/FM 9.0 | placebo HFA pMDI x 1 inhalation + 9 μg formoterol (as 80/4.5 μg Symbicort pMDI x 2 inhalations) |
| OG003 | BUD 160/ Foradil 12.0 | Foradil Aerolizer 12 μg x 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations |
|
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|