COPD, Chronic Obstructive Pulmonary Disease
Conditions
Brief summary
To assess the effect of treatment with Glycopyronnium (GP) MDI administered twice daily (BID) and Formoterol Fumarate (FF) MDI administered BID on specific image-based airway volumes and resistance in subjects with moderate to severe chronic obstructive pulmonary disease (COPD) following chronic dosing after approximately two weeks treatment.
Interventions
DRUGGP MDI (PT001) 14.4 μg
Glycopyrronium
Formoterol Fumarate
Sponsors
Pearl Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Non-child bearing potential (ie, physiologically incapable of becoming pregnant, including any female who is 2 years post-menopausal); or Child bearing potential, has a negative urine pregnancy test at Visit 1, and agrees to use acceptable contraceptive methods used consistently and correctly * Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) * Current or former smokers with a history of at least 10 pack-years of cigarette smoking. * At Visit 1, FEV1/FVC ratio must be \<0.70 * At Visit 1, post-bronchodilator FEV1must be \>30% and \<80% predicted normal value, calculated using The Third National Health and Nutrition Examination Survey (NHANES III) reference equations.
Exclusion criteria
* Significant diseases other than COPD, i.e., disease or condition which, in the opinion of the Investigator, may put the subject at risk because of participation in the study or may influence either the results of the study or the subject's ability to participate in the study. * Women who are pregnant or lactating, or are planning to become pregnant during the course of the study, or women of childbearing potential who are not using an acceptable method of contraception. * Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma. * Subjects who have been hospitalized due to poorly controlled COPD within 3 months prior to Visit 1 (Screening) or during the run-in period (Visit 1 to Visit 2). * Subjects who have poorly controlled COPD, defined as acute worsening of COPD that requires treatment with oral corticosteroids or antibiotics within 6 weeks prior to Visit 1 (Screening) or during the run-in period (Visit 1 to Visit 2). * Subjects with a diagnosis of angle closure glaucoma will be excluded, regardless of whether or not they have been treated. * Subjects who have a history of hypersensitivity to β2-agonists, glycopyrronium or other muscarinic anticholinergics, or any component of the MDI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Specific Image-Based Airway Volume (siVaw) | Baseline, Day 15 | Specific image-based airway volume. Average across lobe, adjusted for lobe volume. Ratio to baseline |
| Specific Image-based Airway Resistance (siRaw) | Baseline, Day 15 | Specific image-based airway resistance (siRaw). Average across lobes, adjusted for lobe volume. Ratio to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Image-based Airway Volume (iVaw) | Baseline, Day 15 | Image-based airway volume (iVaw) without correction for lobe volume. Ratio to baseline. |
| Image-based Airway Resistance (iRaw) | Baseline, Day 15 | Image-based airway resistance (iRaw) without correction for lobe volume. Ratio to baseline. |
| FEV1 | Baseline, Day 15 | FEV1 Change from baseline in Forced Expiratory Volume at 1 second. |
| Functional Residual Capacity (FRC) | Baseline, Day 15 | Functional residual capacity (FRC). Ratio to baseline. |
Countries
Belgium
Participant flow
Recruitment details
This study randomized 23 subjects at 2 sites in Belgium from December 2016 to May 2018.
Pre-assignment details
Subjects were randomized into 1 of 2 treatment sequences. Sequence 1 received GP MDI in Period 1 followed by FF MDI in Period 2. Sequence 2 received FF MDI in Period 1 followed by GP 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 | 1 | 2 |
| Washout | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 64.6 Years STANDARD_DEVIATION 9.6 |
| 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 | 6 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 22 |
| other Total, other adverse events | 3 / 20 | 3 / 22 |
| serious Total, serious adverse events | 1 / 20 | 1 / 22 |
Outcome results
Primary
Specific Image-based Airway Resistance (siRaw)
Specific image-based airway resistance (siRaw). Average across lobes, adjusted for lobe volume. Ratio to baseline.
Time frame: Baseline, Day 15
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| GP MDI | Specific Image-based Airway Resistance (siRaw) | 0.75 ratio |
| FF MDI | Specific Image-based Airway Resistance (siRaw) | 0.56 ratio |
p-value: 0.021995% CI: [0.59, 0.95]t-test, 2 sided
p-value: <0.000195% CI: [0.44, 0.71]t-test, 2 sided
Primary
Specific Image-Based Airway Volume (siVaw)
Specific image-based airway volume. Average across lobe, adjusted for lobe volume. Ratio to baseline
Time frame: Baseline, Day 15
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| GP MDI | Specific Image-Based Airway Volume (siVaw) | 1.11 ratio |
| FF MDI | Specific Image-Based Airway Volume (siVaw) | 1.23 ratio |
p-value: 0.018795% CI: [1.02, 1.22]t-test, 2 sided
p-value: <0.000195% CI: [1.14, 1.33]t-test, 2 sided
Secondary
FEV1
FEV1 Change from baseline in Forced Expiratory Volume at 1 second.
Time frame: Baseline, Day 15
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GP MDI | FEV1 | 0.065 L | Standard Deviation 0.193 |
| FF MDI | FEV1 | 0.151 L | Standard Deviation 0.293 |
p-value: 0.158295% CI: [-0.028, 0.158]t-test, 2 sided
p-value: 0.037595% CI: [0.01, 0.292]t-test, 2 sided
Secondary
Functional Residual Capacity (FRC)
Functional residual capacity (FRC). Ratio to baseline.
Time frame: Baseline, Day 15
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| GP MDI | Functional Residual Capacity (FRC) | 0.978 ratio |
| FF MDI | Functional Residual Capacity (FRC) | 0.938 ratio |
p-value: 0.617695% CI: [0.891, 1.073]t-test, 2 sided
p-value: 0.269995% CI: [0.833, 1.056]t-test, 2 sided
Secondary
Image-based Airway Resistance (iRaw)
Image-based airway resistance (iRaw) without correction for lobe volume. Ratio to baseline.
Time frame: Baseline, Day 15
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| GP MDI | Image-based Airway Resistance (iRaw) | 0.76 ratio |
| FF MDI | Image-based Airway Resistance (iRaw) | 0.55 ratio |
p-value: 0.030495% CI: [0.59, 0.97]t-test, 2 sided
p-value: 0.000395% CI: [0.41, 0.72]t-test, 2 sided
Secondary
Image-based Airway Volume (iVaw)
Image-based airway volume (iVaw) without correction for lobe volume. Ratio to baseline.
Time frame: Baseline, Day 15
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| GP MDI | Image-based Airway Volume (iVaw) | 1.12 ratio |
| FF MDI | Image-based Airway Volume (iVaw) | 1.21 ratio |
p-value: 0.028395% CI: [1.01, 1.24]t-test, 2 sided
p-value: <0.000195% CI: [1.12, 1.31]t-test, 2 sided