COPD
Conditions
Brief summary
Study to Evaluate the Effects of PT003 and Placebo MDI on Specific Image Based Airway Volumes and Resistance With Moderate to Severe COPD.
Detailed description
Enrolled patients with COPD who were randomized to receive either PT003 MDI or Placebo MDI first and then crossed over to receive the opposite intervention. The study consisted of 2 treatment periods of 14 days separated by a washout period of 5-21 days.
Interventions
DRUGGFF MDI (PT003) 14.4/9.6μg
Glycopyrronium and Formoterol Fumarate
DRUGPlacebo MDI
Comparator: Placebo MDI which contains no active ingredients
Sponsors
Pearl Therapeutics, Inc.
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
* 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 an acceptable method of contraception * 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 FEV1/FVC ratio of \<70% and FEV1 must be 30% to 80% before predicted normal value, calculated using 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. Please refer to the study protocol for the complete inclusion criteria list.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Specific Airway Volume (siVaw) | Day 15 | Specific image-based airway volume. Average across lobe, adjusted for lobe volume |
| Specific Airway Resistance (siRaw) | Day 15 | Specific image-based airway resistance. Average across lobes, adjusted for lobe volume |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Airway Resistance (iRaw) | Day 15 | iRaw represents the airway resistance, averaged across lobes, without correction for lung lobe volume |
| Airway Volume (iVaw) | Day 15 | iVaw represents the airway Volume, averaged across lobes, without correction for lung lobe volume |
| Change From Baseline in FEV1 (L) at Day 15 | Baseline and Day 15 | Change from baseline in Forced Expiratory Volume at 1 second |
| Change From Baseline in FRC (L) at Day 15 | Baseline and Day 15 | Change from baseline in Functional Residual Capacity |
Countries
Belgium
Participant flow
Recruitment details
This study was conducted at 1 site in Antwerp Belgium from January 2016 to December 2016.The study was anticipated to run for approximately 9 months but not to expected to exceed 12 months. The study period was duration was expected to run approximately 13 weeks for each subject.
Pre-assignment details
Subjects were randomized into 1 of 2 treatment sequences: subjects in Sequence 1 received GFF MDI in Treatment Period 1 followed by Placebo MDI in Treatment Period 2, and subjects in Sequence 2 received Placebo MDI in Treatment Period 1 followed by GFF MDI in Treatment Period 2. There was a a washout of 5-21 days,in between treatment periods.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study All Randomized Patients | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 64.8 Years STANDARD_DEVIATION 8.7 |
| 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 | 20 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 19 |
| other Total, other adverse events | 15 / 20 | 12 / 20 | 8 / 19 |
| serious Total, serious adverse events | 2 / 20 | 1 / 20 | 1 / 19 |
Outcome results
Primary
Specific Airway Resistance (siRaw)
Specific image-based airway resistance. Average across lobes, adjusted for lobe volume
Time frame: Day 15
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 µg | Specific Airway Resistance (siRaw) | 0.09 kPa s |
| Placebo MDI | Specific Airway Resistance (siRaw) | 0.30 kPa s |
p-value: <0.000195% CI: [0.25, 0.33]Mixed Models Analysis
Primary
Specific Airway Volume (siVaw)
Specific image-based airway volume. Average across lobe, adjusted for lobe volume
Time frame: Day 15
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 µg | Specific Airway Volume (siVaw) | 1.79 mL/L |
| Placebo MDI | Specific Airway Volume (siVaw) | 1.02 mL/L |
p-value: <0.000195% CI: [1.65, 1.86]Mixed Models Analysis
Secondary
Airway Resistance (iRaw)
iRaw represents the airway resistance, averaged across lobes, without correction for lung lobe volume
Time frame: Day 15
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 µg | Airway Resistance (iRaw) | 0.07 kPa s/L |
| Placebo MDI | Airway Resistance (iRaw) | 0.25 kPa s/L |
p-value: <0.000195% CI: [0.26, 0.33]Mixed Models Analysis
Secondary
Airway Volume (iVaw)
iVaw represents the airway Volume, averaged across lobes, without correction for lung lobe volume
Time frame: Day 15
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 µg | Airway Volume (iVaw) | 2.11 mL |
| Placebo MDI | Airway Volume (iVaw) | 1.18 mL |
p-value: <0.000195% CI: [1.67, 1.92]Mixed Models Analysis
Secondary
Change From Baseline in FEV1 (L) at Day 15
Change from baseline in Forced Expiratory Volume at 1 second
Time frame: Baseline and Day 15
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 µg | Change From Baseline in FEV1 (L) at Day 15 | 0.334 Liters |
| Placebo MDI | Change From Baseline in FEV1 (L) at Day 15 | -0.110 Liters |
p-value: <0.000195% CI: [0.318, 0.569]Mixed Models Analysis
Secondary
Change From Baseline in FRC (L) at Day 15
Change from baseline in Functional Residual Capacity
Time frame: Baseline and Day 15
Population: ITT Population
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 µg | Change From Baseline in FRC (L) at Day 15 | 0.90 Liters |
| Placebo MDI | Change From Baseline in FRC (L) at Day 15 | 1.03 Liters |
p-value: <0.000195% CI: [0.82, 0.92]Mixed Models Analysis