Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD
Brief summary
This is a randomised, controlled, two period cross-over, 4 weeks chronic dosing, study to evaluate the effects of Budesonide/Glycopyrronium/Formoterol Fumarate (BGF) and Glycopyrronium/Formoterol Fumarate (GFF) on airway dimensions.
Detailed description
This is a randomised, controlled, two period cross-over, 4 weeks chronic dosing, study to evaluate the effects of Budesonide/Glycopyrronium/Formoterol Fumarate (BGF), and Glycopyrronium/Formoterol Fumarate (GFF), on specific image based airway volumes and resistance in subjects with moderate to severe Chronic Obstructive Pulmonary Disease. In this study, airway dimension parameters will be calculated for each of the active compounds. This imaging methodology will allow an assessment of the extent of airway changes using a triple combination of Budesonide/Glycopyrronium/Formoterol Fumarate (BGF) and the dual combination Glycopyrronium/Formoterol Fumarate (GFF).
Interventions
COMBINATION_PRODUCTBGF
Treatment with Budesonide/Glycopyrronium/FormoterolFumarate
COMBINATION_PRODUCTGFF
Treatment with Glycopyrronium/Formoterol Fumarate
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Subject must be 40 years to ≤80 years of age inclusive, at the time of signing the informed consent form at Visit 1. * COPD Diagnosis: Subjects with an established clinical history of COPD * Screening clinical laboratory tests must be acceptable to the Investigator. * Screening ECG must be acceptable to the Investigator * Individual Compliance: Subjects must be willing to remain at the study center as required per protocol to complete all visit assessments * Patients should be on scheduled maintenance treatment with one or more inhaled bronchodilator therapies.
Exclusion criteria
* As judged by the investigator, any evidence of significant diseases other than COPD, i.e., disease or condition which, in the investigator's opinion makes it undesirable for the subject to participate in the trial. * Spirometry Performance: 1. Subjects who cannot perform acceptable spirometry, i.e., meet ATS/ERS acceptability criteria. 2. Repeatability: Subjects who cannot perform technically acceptable spirometry in accordance with ATS repeatability criteria * Cancer: Subjects who have cancer that has not been in complete remission for at least five years. * Substance Abuse: Subjects, who in the opinion of the Investigator, significantly abuse alcohol or drugs * Subjects who in the opinion of the investigator are unable to abstain from prohibited medications including LABA/LAMAs/ICS
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Specific Image-based Airway Volume (siVaw) | Baseline, Day 29 | Specific image-based airway volume (SiVaw) measured in mL/L. Average across lobes, adjusted for lobe volume. Reported as ratio to baseline. |
| Specific Image-based Airway Resistance (siRaw) | Baseline, Day 29 | Specific image-based airway resistance (siRaw) measured in kPa∙s. Average across lobes, adjusted for lobe volume. Reported as ratio to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Image-based Airway Volume (iVaw) | Baseline, Day 29 | Image-based Airway Volume (iVaw) measured in mL. Average across lobes, without adjustment for lobe volume. Reported as ratio to baseline. |
| Image-based Airway Resistance (iRaw) | Baseline, 29 Days | Image-based airway resistance (iRaw) measured in kPa∙s/L. Average across lobes, without adjustment for lobe volume. Reported as ratio to baseline. |
| Forced Expiratory Volume in One Second (Post-dose FEV1). | Baseline 29 Days | Change from baseline in Forced Expiratory Volume in One Second (Post-dose FEV1). |
| Functional Residual Capacity (FRC) | Baseline, Day 29 | Change from baseline in Functional residual capacity (FRC). |
Countries
Belgium, Netherlands
Participant flow
Recruitment details
This study randomized 23 subjects at 4 study centers (1 center in Belgium and 3 centers in the Netherlands) from Feb 2019 to Nov 2019.
Pre-assignment details
Subjects were randomized into 1 of 2 treatment sequences. Sequence 1 received BGF MDI in Period 1 followed by GFF MDI in Period 2. Sequence 2 received GFF MDI in Period 1 followed by BGF MDI in Period 2.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study ITT Population | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 0 | 1 |
| Period 2 | Severe non-compliance to protocol | 1 | 0 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 64.9 Years STANDARD_DEVIATION 7.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 23 |
| other Total, other adverse events | 0 / 22 | 2 / 23 |
| serious Total, serious adverse events | 1 / 22 | 0 / 23 |
Outcome results
Primary
Specific Image-based Airway Resistance (siRaw)
Specific image-based airway resistance (siRaw) measured in kPa∙s. Average across lobes, adjusted for lobe volume. Reported as ratio to baseline.
Time frame: Baseline, Day 29
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| BGF MDI | Specific Image-based Airway Resistance (siRaw) | 0.50 Ratio to baseline |
| GFF MDI | Specific Image-based Airway Resistance (siRaw) | 0.52 Ratio to baseline |
p-value: <0.000195% CI: [0.39, 0.63]t-test, 2 sided
p-value: <0.000195% CI: [0.4, 0.67]t-test, 2 sided
Primary
Specific Image-based Airway Volume (siVaw)
Specific image-based airway volume (SiVaw) measured in mL/L. Average across lobes, adjusted for lobe volume. Reported as ratio to baseline.
Time frame: Baseline, Day 29
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| BGF MDI | Specific Image-based Airway Volume (siVaw) | 1.72 Ratio to baseline |
| GFF MDI | Specific Image-based Airway Volume (siVaw) | 1.53 Ratio to baseline |
p-value: <0.000195% CI: [1.38, 2.13]t-test, 2 sided
p-value: <0.000195% CI: [1.28, 1.83]t-test, 2 sided
Secondary
Forced Expiratory Volume in One Second (Post-dose FEV1).
Change from baseline in Forced Expiratory Volume in One Second (Post-dose FEV1).
Time frame: Baseline 29 Days
Population: ITT Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BGF MDI | Forced Expiratory Volume in One Second (Post-dose FEV1). | 0.346 L |
| GFF MDI | Forced Expiratory Volume in One Second (Post-dose FEV1). | 0.273 L |
p-value: 0.000395% CI: [0.182, 0.509]t-test, 2 sided
p-value: 0.000495% CI: [0.14, 0.405]t-test, 2 sided
Secondary
Functional Residual Capacity (FRC)
Change from baseline in Functional residual capacity (FRC).
Time frame: Baseline, Day 29
Population: ITT Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BGF MDI | Functional Residual Capacity (FRC) | -0.28 L |
| GFF MDI | Functional Residual Capacity (FRC) | -0.50 L |
p-value: 0.251595% CI: [-0.77, 0.21]t-test, 2 sided
p-value: 0.00495% CI: [-0.81, -0.18]t-test, 2 sided
Secondary
Image-based Airway Resistance (iRaw)
Image-based airway resistance (iRaw) measured in kPa∙s/L. Average across lobes, without adjustment for lobe volume. Reported as ratio to baseline.
Time frame: Baseline, 29 Days
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| BGF MDI | Image-based Airway Resistance (iRaw) | 0.50 Ratio to baseline |
| GFF MDI | Image-based Airway Resistance (iRaw) | 0.52 Ratio to baseline |
p-value: <0.000195% CI: [0.4, 0.63]t-test, 2 sided
p-value: <0.000195% CI: [0.4, 0.68]t-test, 2 sided
Secondary
Image-based Airway Volume (iVaw)
Image-based Airway Volume (iVaw) measured in mL. Average across lobes, without adjustment for lobe volume. Reported as ratio to baseline.
Time frame: Baseline, Day 29
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| BGF MDI | Image-based Airway Volume (iVaw) | 1.70 Ratio to baseline |
| GFF MDI | Image-based Airway Volume (iVaw) | 1.51 Ratio to baseline |
p-value: <0.000195% CI: [1.37, 2.11]t-test, 2 sided
p-value: 0.000195% CI: [1.26, 1.8]t-test, 2 sided