Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD
Brief summary
Study comparing the same drugs as a dual combination product (budesonide and formoterol) given via two different inhalers. To see which one results in the best effect on breathing.
Detailed description
This is a Randomized, Open-Label, Two Period Crossover, Chronic Dosing, 1-Week, Pilot Study to Assess the Efficacy and Safety of Budesonide and Formoterol Fumarate Inhalation Aerosol Administered with a Spacer Compared with Symbicort® Turbuhaler® in Subjects with Severe to Very Severe Chronic Obstructive Pulmonary Disease and Low Peak Inspiratory Flow to assess lung function
Interventions
COMBINATION_PRODUCTBFF
Treatment with budesonide and formoterol furmate MDI (metered-dose inhaler)
COMBINATION_PRODUCTSymbicort Turbuhaler
Treatment with budesonide and formoterol furmate DPI (dry-powder inhaler)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Subject must be 40 to 80 years of age inclusive, at the time of signing the ICF. 2. Individuals who have a physician diagnosis of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) 3. Require COPD maintenance therapy: all subjects must be receiving 2 or more inhaled maintenance therapies, including at least 1 long-acting bronchodilator, for the management of their COPD for at least 4 weeks prior to Visit 1. 4. A post-bronchodilator FEV1/FVC of \<0.70 and post-bronchodilator FEV1 of \<50% predicted normal value at Visit 2. 5. A pre-bronchodilator PIF of \<50 L/min using the InCheck Inspiratory Flow Measurement Device set to Turbuhaler S resistance at Visit 2. 6. Current or former smokers with history of at least 10 pack-years of cigarette smoking. Key
Exclusion criteria
1. Current diagnosis of asthma, in the opinion of the Investigator. 2. Other respiratory disorders including known active tuberculosis, lung cancer, cystic fibrosis, significant bronchiectasis (high resolution CT evidence of bronchiectasis that causes repeated acute exacerbations), immune deficiency disorders, severe neurological disorders affecting control of the upper airway, sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary pulmonary hypertension, or pulmonary thromboembolic disease. 3. A moderate or severe exacerbation of COPD ending within 6 weeks prior to randomization (Visit 3). 4. Need for mechanical ventilation within 3 months prior to Visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Within 4 Hours Post-dose Following 1 Week of Treatment | baseline and 4 hours post dose after 1 week of treatment | Peak change from baseline in FEV1 within 4 hours post-dose was defined as the maximum of the FEV1 assessments within 4 hours post-dosing at each visit minus baseline, provided that there were at least 2 non-missing values during the first 4 hours post dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pre-dose FEV1 Following 1 Week of Treatment | baseline and after 1 week of treatment | Change from baseline in pre-dose FEV1 following 1 week of treatment was defined as the 45-minute pre-dose value following 1 week of treatment minus baseline. |
| Change From Baseline in 2-hour Post-dose Inspiratory Capacity (IC) Following 1 Week of Treatment | baseline and 2 hours post dose after 1 week of treatment | Change from baseline in 2-hour post-dose IC following 1 week of treatment was defined as the 2-hour post-dose assessment of IC following 1 week of treatment minus baseline IC. |
| Change From Baseline in Pre-dose Peak Inspiratory Flow (PIF; InCheck Device Set to no Resistance) Following 1 Week of Treatment | baseline and after 1 week of treatment | Change from baseline in pre-dose PIF (InCheck device set to no resistance) following 1 week of treatment was defined as the pre-dose PIF (InCheck device set to no resistance) following 1 week of treatment minus baseline PIF. (The InCheck Inspiratory Flow Measurement Device is an inhalation airflow meter that may be set to various resistances similar to marketed inhaler products. For this measurement, the device was set to no resistance.) |
| Area Under the Curve for Change From Baseline in FEV1 From Area Under the Curve 0 to 4 Hours (AUC0-4 h) Following 1 Week of Treatment | baseline and 4 hours post dose after 1 week of treatment | FEV1 AUC0-4 was calculated using the trapezoidal rule and was normalized by dividing by the time in hours from dosing to the last measurement included (typically 4 hours). |
| Change From Baseline in Pre-dose PIF (Resistance Set Equal to ELLIPTA) Following 1 Week of Treatment | baseline and after 1 week of treatment | Change from baseline in pre-dose PIF (resistance set equal to ELLIPTA) following 1 week of treatment was defined as the pre-dose PIF (resistance set equal to ELLIPTA) following 1 week of treatment minus baseline PIF. (The InCheck Inspiratory Flow Measurement Device is an inhalation airflow meter that may be set to various resistances similar to marketed inhaler products. For this measurement, the device was set to resistance equal to the product ELLIPTA.) |
| Change From Baseline in 2-hour Post-dose FEV1 Following the First Dose | baseline and 2 hours post dose after the first dose of treatment | Change from baseline in 2-hour post-dose FEV1 following the 1st dose of treatment was defined as the 2-hour post-dose assessment of FEV1 following the 1st dose of treatment (Visit 3 or 5) minus baseline FEV1. |
| Change From Baseline in 2-hour Post-dose IC Following the First Dose | baseline and 2 hours post dose after the first dose of treatment | Change from baseline in 2-hour post-dose IC following the 1st dose of treatment was defined as the 2-hour post-dose assessment of IC following the 1st dose of treatment (Visit 3 or 5) minus baseline IC. |
| Change From Baseline in Pre-dose PIF (Resistance Set Equal to Turbuhaler S) Following 1 Week of Treatment | baseline and after 1 week of treatment | Change from baseline in pre-dose PIF (resistance set equal to Turbuhaler S) following 1 week of treatment was defined as the pre-dose PIF (resistance set equal to Turbuhaler S) following 1 week of treatment minus baseline PIF. (The InCheck Inspiratory Flow Measurement Device is an inhalation airflow meter that may be set to various resistances similar to marketed inhaler products. For this measurement, the device was set to resistance equal to the product Turbuhaler S.) |
Countries
Germany
Participant flow
Recruitment details
This study started recruitment in September 2019 with first subject randomized in January 2020. A total of 35 subjects were randomized at 4 study centers. The study completed in Dec 2020.
Pre-assignment details
Subjects were randomized to an open-label, 2 period crossover study comparing Budesonide Formoterol Fumarate (BFF) Metered Dose Inhalation (MDI) administered with a spacer twice daily (BID) with Symbicort Turbuhaler BID. The subjects underwent an intervening two-week washout period where they used Berodual and Budesonide MDI BID.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Intent-to-Treat (ITT) Population | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2 | Study put on hold due to COVID-19 | 1 | 1 |
| Washout | Study put on hold due to COVID-19 | 0 | 2 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous Mean age (SD), years | 65.8 Years STANDARD_DEVIATION 5.5 |
| Race (NIH/OMB) Race for all subjects American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Race for all subjects Asian | 0 Participants |
| Race (NIH/OMB) Race for all subjects Black or African American | 0 Participants |
| Race (NIH/OMB) Race for all subjects More than one race | 0 Participants |
| Race (NIH/OMB) Race for all subjects Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Race for all subjects Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) Race for all subjects White | 35 Participants |
| Sex: Female, Male Distribution of Male/Female Participants Female | 19 Participants |
| Sex: Female, Male Distribution of Male/Female Participants Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 35 |
| other Total, other adverse events | 1 / 33 | 1 / 35 |
| serious Total, serious adverse events | 0 / 33 | 0 / 35 |
Outcome results
Primary
Peak Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Within 4 Hours Post-dose Following 1 Week of Treatment
Peak change from baseline in FEV1 within 4 hours post-dose was defined as the maximum of the FEV1 assessments within 4 hours post-dosing at each visit minus baseline, provided that there were at least 2 non-missing values during the first 4 hours post dose.
Time frame: baseline and 4 hours post dose after 1 week of treatment
Population: Modified Intent-to-treat (mITT) Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BFF MDI | Peak Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Within 4 Hours Post-dose Following 1 Week of Treatment | 0.256 L |
| Symbicort Turbuhaler | Peak Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Within 4 Hours Post-dose Following 1 Week of Treatment | 0.274 L |
p-value: 0.34595% CI: [-0.054, 0.02]ANCOVA
Secondary
Area Under the Curve for Change From Baseline in FEV1 From Area Under the Curve 0 to 4 Hours (AUC0-4 h) Following 1 Week of Treatment
FEV1 AUC0-4 was calculated using the trapezoidal rule and was normalized by dividing by the time in hours from dosing to the last measurement included (typically 4 hours).
Time frame: baseline and 4 hours post dose after 1 week of treatment
Population: mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BFF MDI | Area Under the Curve for Change From Baseline in FEV1 From Area Under the Curve 0 to 4 Hours (AUC0-4 h) Following 1 Week of Treatment | 0.194 L |
| Symbicort Turbuhaler | Area Under the Curve for Change From Baseline in FEV1 From Area Under the Curve 0 to 4 Hours (AUC0-4 h) Following 1 Week of Treatment | 0.210 L |
p-value: 0.367595% CI: [-0.054, 0.021]ANCOVA
Secondary
Change From Baseline in 2-hour Post-dose FEV1 Following the First Dose
Change from baseline in 2-hour post-dose FEV1 following the 1st dose of treatment was defined as the 2-hour post-dose assessment of FEV1 following the 1st dose of treatment (Visit 3 or 5) minus baseline FEV1.
Time frame: baseline and 2 hours post dose after the first dose of treatment
Population: mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BFF MDI | Change From Baseline in 2-hour Post-dose FEV1 Following the First Dose | 0.136 L |
| Symbicort Turbuhaler | Change From Baseline in 2-hour Post-dose FEV1 Following the First Dose | 0.093 L |
p-value: 0.037595% CI: [0.003, 0.084]ANCOVA
Secondary
Change From Baseline in 2-hour Post-dose IC Following the First Dose
Change from baseline in 2-hour post-dose IC following the 1st dose of treatment was defined as the 2-hour post-dose assessment of IC following the 1st dose of treatment (Visit 3 or 5) minus baseline IC.
Time frame: baseline and 2 hours post dose after the first dose of treatment
Population: mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BFF MDI | Change From Baseline in 2-hour Post-dose IC Following the First Dose | 0.264 L |
| Symbicort Turbuhaler | Change From Baseline in 2-hour Post-dose IC Following the First Dose | 0.258 L |
p-value: 0.908995% CI: [-0.086, 0.096]ANCOVA
Secondary
Change From Baseline in 2-hour Post-dose Inspiratory Capacity (IC) Following 1 Week of Treatment
Change from baseline in 2-hour post-dose IC following 1 week of treatment was defined as the 2-hour post-dose assessment of IC following 1 week of treatment minus baseline IC.
Time frame: baseline and 2 hours post dose after 1 week of treatment
Population: mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BFF MDI | Change From Baseline in 2-hour Post-dose Inspiratory Capacity (IC) Following 1 Week of Treatment | 0.379 L |
| Symbicort Turbuhaler | Change From Baseline in 2-hour Post-dose Inspiratory Capacity (IC) Following 1 Week of Treatment | 0.411 L |
p-value: 0.541995% CI: [-0.139, 0.075]ANCOVA
Secondary
Change From Baseline in Pre-dose FEV1 Following 1 Week of Treatment
Change from baseline in pre-dose FEV1 following 1 week of treatment was defined as the 45-minute pre-dose value following 1 week of treatment minus baseline.
Time frame: baseline and after 1 week of treatment
Population: mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BFF MDI | Change From Baseline in Pre-dose FEV1 Following 1 Week of Treatment | 0.081 L |
| Symbicort Turbuhaler | Change From Baseline in Pre-dose FEV1 Following 1 Week of Treatment | 0.087 L |
p-value: 0.756395% CI: [-0.047, 0.034]ANCOVA
Secondary
Change From Baseline in Pre-dose Peak Inspiratory Flow (PIF; InCheck Device Set to no Resistance) Following 1 Week of Treatment
Change from baseline in pre-dose PIF (InCheck device set to no resistance) following 1 week of treatment was defined as the pre-dose PIF (InCheck device set to no resistance) following 1 week of treatment minus baseline PIF. (The InCheck Inspiratory Flow Measurement Device is an inhalation airflow meter that may be set to various resistances similar to marketed inhaler products. For this measurement, the device was set to no resistance.)
Time frame: baseline and after 1 week of treatment
Population: mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BFF MDI | Change From Baseline in Pre-dose Peak Inspiratory Flow (PIF; InCheck Device Set to no Resistance) Following 1 Week of Treatment | 1.50 L/min |
| Symbicort Turbuhaler | Change From Baseline in Pre-dose Peak Inspiratory Flow (PIF; InCheck Device Set to no Resistance) Following 1 Week of Treatment | 5.11 L/min |
p-value: 0.133795% CI: [-8.39, 1.18]ANCOVA
Secondary
Change From Baseline in Pre-dose PIF (Resistance Set Equal to ELLIPTA) Following 1 Week of Treatment
Change from baseline in pre-dose PIF (resistance set equal to ELLIPTA) following 1 week of treatment was defined as the pre-dose PIF (resistance set equal to ELLIPTA) following 1 week of treatment minus baseline PIF. (The InCheck Inspiratory Flow Measurement Device is an inhalation airflow meter that may be set to various resistances similar to marketed inhaler products. For this measurement, the device was set to resistance equal to the product ELLIPTA.)
Time frame: baseline and after 1 week of treatment
Population: mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BFF MDI | Change From Baseline in Pre-dose PIF (Resistance Set Equal to ELLIPTA) Following 1 Week of Treatment | 1.21 L/min |
| Symbicort Turbuhaler | Change From Baseline in Pre-dose PIF (Resistance Set Equal to ELLIPTA) Following 1 Week of Treatment | 2.74 L/min |
p-value: 0.362595% CI: [-4.87, 1.81]ANCOVA
Secondary
Change From Baseline in Pre-dose PIF (Resistance Set Equal to Turbuhaler S) Following 1 Week of Treatment
Change from baseline in pre-dose PIF (resistance set equal to Turbuhaler S) following 1 week of treatment was defined as the pre-dose PIF (resistance set equal to Turbuhaler S) following 1 week of treatment minus baseline PIF. (The InCheck Inspiratory Flow Measurement Device is an inhalation airflow meter that may be set to various resistances similar to marketed inhaler products. For this measurement, the device was set to resistance equal to the product Turbuhaler S.)
Time frame: baseline and after 1 week of treatment
Population: mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BFF MDI | Change From Baseline in Pre-dose PIF (Resistance Set Equal to Turbuhaler S) Following 1 Week of Treatment | 1.13 L/min |
| Symbicort Turbuhaler | Change From Baseline in Pre-dose PIF (Resistance Set Equal to Turbuhaler S) Following 1 Week of Treatment | 3.82 L/min |
p-value: 0.043195% CI: [-5.29, -0.09]ANCOVA