Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD
Brief summary
The primary objective of this study is to demonstrate efficacy of PT003 MDI relative to its individual components (PT001 MDI and PT005 MDI) in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
Interventions
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
Key Inclusion Criteria: * Signed written informed consent * 40 - 80 years of age * Clinical history of COPD with airflow limitation that is not fully reversible * Females of non-child bearing potential or females of child bearing potential with negative pregnancy test; and acceptable contraceptive methods * Current/former smokers with at least a 10 pack-year history of cigarette smoking * A measured post- bronchodilator FEV1/FVC ratio of \< or = 0.70 * A measured post- bronchodilator FEV1 \> or = 750ml or 30% predicted and \< or = 80% of predicted normal values * Able to change COPD treatment as required by protocol Key
Exclusion criteria
* Women who are pregnant or lactating * Primary diagnosis of asthma * Alpha-1 antitrypsin deficiency as the cause of COPD * Active pulmonary diseases * Prior lung volume reduction surgery * Abnormal chest X-ray (or CT scan) not due to the presence of COPD * Hospitalized due to poorly controlled COPD within 3 months of Screening * Clinically significant medical conditions that preclude participation in the study (e.g. clinically significant abnormal ECG, uncontrolled hypertension, glaucoma, symptomatic prostatic hypertrophy) * Cancer that has not been in complete remission for at least 5 years * Treatment with investigational study drug or participation in another clinical trial or study within the last 30 days or 5 half lives Other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 AUC0-12 | Day 7 | Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 relative to baseline following chronic dosing (1 week). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of Action | Day 1 | At least 10% improvement in mean FEV1 |
| At Least 12% Improvement in FEV1 | Day 1 | Proportion of subjects achieving \>=12% improvement in FEV1 relative to baseline |
| Peak Change in IC | Day 1 | Mean inspiratory capacity (IC) of 1 and 2 hours post-dose minus baseline |
| Peak Change From Baseline in FEV1 | Day 1 | Peak change from baseline in FEV1 through 2 hours |
| FEV1 Through 6 Hours | Day 7 | Peak change from baseline in FEV1 through 6 hours |
| Peak Change From Baseline in IC | Day 7 | Peak change from baseline in inspiratory capacity (IC) (mean of 1 and 2 hours post-dose minus baseline) |
| Mean Evening Trough FEV1 | Day 7 | Change from baseline in mean evening 12-hour post-dose trough FEV1 |
| Morning Pre-dose FEV1 | Day 7 | Change from baseline in morning pre-dose FEV1 (average of 60- and 30-minute pre-dose values on Day 7) |
Countries
United States
Participant flow
Recruitment details
Conducted at 14 US sites from July-November 2011. Entire study period of study participation was a maximum of 9 weeks.
Pre-assignment details
Study was a chronic dosing study; each participant received 2 of 6 possible treatments; each treatment period was separated by a washout period of at least 7 days. Patients were randomized into one of 30 treatment sequences. Each sequence included exactly 2 of the 6 treatment groups for this study.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study All patients randomized and treated | 185 |
| Total | 185 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 14 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol-specified criteria | 8 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 62.1 Years STANDARD_DEVIATION 9.18 |
| Sex: Female, Male Female | 78 Participants |
| Sex: Female, Male Male | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 58 | 4 / 56 | 1 / 57 | 7 / 57 | 2 / 61 | 8 / 61 |
| serious Total, serious adverse events | 1 / 58 | 0 / 56 | 0 / 57 | 0 / 57 | 2 / 61 | 0 / 61 |
Outcome results
Primary
FEV1 AUC0-12
Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 relative to baseline following chronic dosing (1 week).
Time frame: Day 7
Population: Modified Intent to Treat (MITT) Population is made of participants who completed both treatment periods and had Pre-dose Day 1 data for both and no protocol deviations believed to have a potential impact on efficacy results. Subjects must have had data for the given endpoint to be included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 36/7.2 µg | FEV1 AUC0-12 | 1.467 Liters |
| GFF MDI 36/9.6 µg | FEV1 AUC0-12 | 1.462 Liters |
| GFF MDI 18/9.6 µg | FEV1 AUC0-12 | 1.493 Liters |
| GFF MDI 9/9.6 µg | FEV1 AUC0-12 | 1.499 Liters |
| GP MDI 36 µg | FEV1 AUC0-12 | 1.399 Liters |
| FF MDI 9.6 µg | FEV1 AUC0-12 | 1.465 Liters |
Secondary
At Least 12% Improvement in FEV1
Proportion of subjects achieving \>=12% improvement in FEV1 relative to baseline
Time frame: Day 1
Population: MITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GFF MDI 36/7.2 µg | At Least 12% Improvement in FEV1 | No onset within 2 hours | 10 Participants |
| GFF MDI 36/7.2 µg | At Least 12% Improvement in FEV1 | 30 minutes | 14 Participants |
| GFF MDI 36/7.2 µg | At Least 12% Improvement in FEV1 | 15 minutes | 22 Participants |
| GFF MDI 36/7.2 µg | At Least 12% Improvement in FEV1 | 1 hour | 2 Participants |
| GFF MDI 36/7.2 µg | At Least 12% Improvement in FEV1 | 2 hours | 2 Participants |
| GFF MDI 36/9.6 µg | At Least 12% Improvement in FEV1 | 2 hours | 3 Participants |
| GFF MDI 36/9.6 µg | At Least 12% Improvement in FEV1 | 15 minutes | 17 Participants |
| GFF MDI 36/9.6 µg | At Least 12% Improvement in FEV1 | No onset within 2 hours | 8 Participants |
| GFF MDI 36/9.6 µg | At Least 12% Improvement in FEV1 | 1 hour | 5 Participants |
| GFF MDI 36/9.6 µg | At Least 12% Improvement in FEV1 | 30 minutes | 10 Participants |
| GFF MDI 18/9.6 µg | At Least 12% Improvement in FEV1 | 1 hour | 6 Participants |
| GFF MDI 18/9.6 µg | At Least 12% Improvement in FEV1 | No onset within 2 hours | 8 Participants |
| GFF MDI 18/9.6 µg | At Least 12% Improvement in FEV1 | 2 hours | 5 Participants |
| GFF MDI 18/9.6 µg | At Least 12% Improvement in FEV1 | 15 minutes | 18 Participants |
| GFF MDI 18/9.6 µg | At Least 12% Improvement in FEV1 | 30 minutes | 8 Participants |
| GFF MDI 9/9.6 µg | At Least 12% Improvement in FEV1 | 15 minutes | 27 Participants |
| GFF MDI 9/9.6 µg | At Least 12% Improvement in FEV1 | 2 hours | 6 Participants |
| GFF MDI 9/9.6 µg | At Least 12% Improvement in FEV1 | 30 minutes | 7 Participants |
| GFF MDI 9/9.6 µg | At Least 12% Improvement in FEV1 | 1 hour | 4 Participants |
| GFF MDI 9/9.6 µg | At Least 12% Improvement in FEV1 | No onset within 2 hours | 8 Participants |
| GP MDI 36 µg | At Least 12% Improvement in FEV1 | 2 hours | 4 Participants |
| GP MDI 36 µg | At Least 12% Improvement in FEV1 | 30 minutes | 12 Participants |
| GP MDI 36 µg | At Least 12% Improvement in FEV1 | 15 minutes | 13 Participants |
| GP MDI 36 µg | At Least 12% Improvement in FEV1 | No onset within 2 hours | 17 Participants |
| GP MDI 36 µg | At Least 12% Improvement in FEV1 | 1 hour | 5 Participants |
| FF MDI 9.6 µg | At Least 12% Improvement in FEV1 | No onset within 2 hours | 7 Participants |
| FF MDI 9.6 µg | At Least 12% Improvement in FEV1 | 30 minutes | 10 Participants |
| FF MDI 9.6 µg | At Least 12% Improvement in FEV1 | 1 hour | 7 Participants |
| FF MDI 9.6 µg | At Least 12% Improvement in FEV1 | 2 hours | 5 Participants |
| FF MDI 9.6 µg | At Least 12% Improvement in FEV1 | 15 minutes | 22 Participants |
Secondary
FEV1 Through 6 Hours
Peak change from baseline in FEV1 through 6 hours
Time frame: Day 7
Population: MITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 36/7.2 µg | FEV1 Through 6 Hours | 0.362 Liters |
| GFF MDI 36/9.6 µg | FEV1 Through 6 Hours | 0.356 Liters |
| GFF MDI 18/9.6 µg | FEV1 Through 6 Hours | 0.388 Liters |
| GFF MDI 9/9.6 µg | FEV1 Through 6 Hours | 0.415 Liters |
| GP MDI 36 µg | FEV1 Through 6 Hours | 0.283 Liters |
| FF MDI 9.6 µg | FEV1 Through 6 Hours | 0.355 Liters |
Secondary
Mean Evening Trough FEV1
Change from baseline in mean evening 12-hour post-dose trough FEV1
Time frame: Day 7
Population: MITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 36/7.2 µg | Mean Evening Trough FEV1 | 0.080 Liters |
| GFF MDI 36/9.6 µg | Mean Evening Trough FEV1 | 0.073 Liters |
| GFF MDI 18/9.6 µg | Mean Evening Trough FEV1 | 0.105 Liters |
| GFF MDI 9/9.6 µg | Mean Evening Trough FEV1 | 0.112 Liters |
| GP MDI 36 µg | Mean Evening Trough FEV1 | 0.081 Liters |
| FF MDI 9.6 µg | Mean Evening Trough FEV1 | 0.120 Liters |
Secondary
Morning Pre-dose FEV1
Change from baseline in morning pre-dose FEV1 (average of 60- and 30-minute pre-dose values on Day 7)
Time frame: Day 7
Population: MITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 36/7.2 µg | Morning Pre-dose FEV1 | 0.152 Liters |
| GFF MDI 36/9.6 µg | Morning Pre-dose FEV1 | 0.110 Liters |
| GFF MDI 18/9.6 µg | Morning Pre-dose FEV1 | 0.122 Liters |
| GFF MDI 9/9.6 µg | Morning Pre-dose FEV1 | 0.131 Liters |
| GP MDI 36 µg | Morning Pre-dose FEV1 | 0.100 Liters |
| FF MDI 9.6 µg | Morning Pre-dose FEV1 | 0.103 Liters |
Secondary
Peak Change From Baseline in FEV1
Peak change from baseline in FEV1 through 2 hours
Time frame: Day 1
Population: MITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 36/7.2 µg | Peak Change From Baseline in FEV1 | 0.312 Liters |
| GFF MDI 36/9.6 µg | Peak Change From Baseline in FEV1 | 0.308 Liters |
| GFF MDI 18/9.6 µg | Peak Change From Baseline in FEV1 | 0.344 Liters |
| GFF MDI 9/9.6 µg | Peak Change From Baseline in FEV1 | 0.350 Liters |
| GP MDI 36 µg | Peak Change From Baseline in FEV1 | 0.248 Liters |
| FF MDI 9.6 µg | Peak Change From Baseline in FEV1 | 0.307 Liters |
Secondary
Peak Change From Baseline in IC
Peak change from baseline in inspiratory capacity (IC) (mean of 1 and 2 hours post-dose minus baseline)
Time frame: Day 7
Population: MITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 36/7.2 µg | Peak Change From Baseline in IC | 0.333 Liters |
| GFF MDI 36/9.6 µg | Peak Change From Baseline in IC | 0.267 Liters |
| GFF MDI 18/9.6 µg | Peak Change From Baseline in IC | 0.340 Liters |
| GFF MDI 9/9.6 µg | Peak Change From Baseline in IC | 0.351 Liters |
| GP MDI 36 µg | Peak Change From Baseline in IC | 0.228 Liters |
| FF MDI 9.6 µg | Peak Change From Baseline in IC | 0.354 Liters |
Secondary
Peak Change in IC
Mean inspiratory capacity (IC) of 1 and 2 hours post-dose minus baseline
Time frame: Day 1
Population: MITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 36/7.2 µg | Peak Change in IC | 0.323 Liters |
| GFF MDI 36/9.6 µg | Peak Change in IC | 0.242 Liters |
| GFF MDI 18/9.6 µg | Peak Change in IC | 0.339 Liters |
| GFF MDI 9/9.6 µg | Peak Change in IC | 0.326 Liters |
| GP MDI 36 µg | Peak Change in IC | 0.228 Liters |
| FF MDI 9.6 µg | Peak Change in IC | 0.316 Liters |
Secondary
Time to Onset of Action
At least 10% improvement in mean FEV1
Time frame: Day 1
Population: MITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GFF MDI 36/7.2 µg | Time to Onset of Action | 2 hours | 4 Participants |
| GFF MDI 36/7.2 µg | Time to Onset of Action | 30 minutes | 10 Participants |
| GFF MDI 36/7.2 µg | Time to Onset of Action | 15 minutes | 28 Participants |
| GFF MDI 36/7.2 µg | Time to Onset of Action | No onset within 2 hours | 4 Participants |
| GFF MDI 36/7.2 µg | Time to Onset of Action | 1 hour | 4 Participants |
| GFF MDI 36/9.6 µg | Time to Onset of Action | 30 minutes | 9 Participants |
| GFF MDI 36/9.6 µg | Time to Onset of Action | 2 hours | 2 Participants |
| GFF MDI 36/9.6 µg | Time to Onset of Action | 15 minutes | 21 Participants |
| GFF MDI 36/9.6 µg | Time to Onset of Action | No onset within 2 hours | 8 Participants |
| GFF MDI 36/9.6 µg | Time to Onset of Action | 1 hour | 3 Participants |
| GFF MDI 18/9.6 µg | Time to Onset of Action | 30 minutes | 8 Participants |
| GFF MDI 18/9.6 µg | Time to Onset of Action | 2 hours | 2 Participants |
| GFF MDI 18/9.6 µg | Time to Onset of Action | No onset within 2 hours | 6 Participants |
| GFF MDI 18/9.6 µg | Time to Onset of Action | 1 hour | 9 Participants |
| GFF MDI 18/9.6 µg | Time to Onset of Action | 15 minutes | 20 Participants |
| GFF MDI 9/9.6 µg | Time to Onset of Action | 1 hour | 5 Participants |
| GFF MDI 9/9.6 µg | Time to Onset of Action | 15 minutes | 30 Participants |
| GFF MDI 9/9.6 µg | Time to Onset of Action | 30 minutes | 8 Participants |
| GFF MDI 9/9.6 µg | Time to Onset of Action | 2 hours | 3 Participants |
| GFF MDI 9/9.6 µg | Time to Onset of Action | No onset within 2 hours | 6 Participants |
| GP MDI 36 µg | Time to Onset of Action | 2 hours | 3 Participants |
| GP MDI 36 µg | Time to Onset of Action | 15 minutes | 15 Participants |
| GP MDI 36 µg | Time to Onset of Action | No onset within 2 hours | 12 Participants |
| GP MDI 36 µg | Time to Onset of Action | 30 minutes | 14 Participants |
| GP MDI 36 µg | Time to Onset of Action | 1 hour | 7 Participants |
| FF MDI 9.6 µg | Time to Onset of Action | 15 minutes | 24 Participants |
| FF MDI 9.6 µg | Time to Onset of Action | 2 hours | 2 Participants |
| FF MDI 9.6 µg | Time to Onset of Action | 30 minutes | 14 Participants |
| FF MDI 9.6 µg | Time to Onset of Action | No onset within 2 hours | 5 Participants |
| FF MDI 9.6 µg | Time to Onset of Action | 1 hour | 6 Participants |