Chronic Obstructive Pulmonary Disorder
Conditions
Keywords
COPD
Brief summary
This is a Phase III randomized, double-blind, parallel group, multi-center, 52-week COPD exacerbation and lung function study with PT009 320/9.6 μg, PT009 160/9.6 μg and PT005 9.6 μg, all administered BID.
Detailed description
This is a Phase III randomized, double-blind, parallel group, multi-center, 52-week COPD exacerbation and lung function study. Subjects will undergo a 1- to 4-week Screening Period. Subjects who successfully complete the Screening Period will be randomized to one of the following three treatment groups: PT009 320/9.6 μg, PT009 160/9.6 μg and PT005 9.6 μg, all administered BID. Following randomization, subjects will enter the Treatment Period and undergo additional treatment visits over 52 weeks.
Interventions
Blinded Treatment
DRUGBFF MDI (PT009) 160/9.6 μg
Blinded Treatment
Blinded Treatment
Sponsors
Pearl Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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
1. Give their signed written informed consent to participate 2. At least 40 years of age and no older than 80 years of age 3. COPD patients who are symptomatic 4. Must be receiving one or more inhaled bronchodilators as maintenance therapy 5. Must have a documented history of COPD exacerbations
Exclusion criteria
1. Current diagnosis of asthma 2. COPD due to α1-Antitrypsin Deficiency 3. Known active tuberculosis, lung cancer, cystic fibrosis, and significant bronchiectasis, Pulmonary resection or Lung Volume Reduction Surgery during the past 6 months. 4. Long-term-oxygen therapy (≥ 15 hours a day).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Morning Pre-dose Trough FEV1 | at Week 12 | Morning pre-dose trough FEV1 (Forced Expiratory Volume in one second) at week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Moderate or Severe COPD Exacerbation | over 52 weeks | Time to first moderate or severe COPD (Chronic Obstructive Pulmonary Disease) exacerbation over 52 weeks |
| Change From Baseline in Average Daily Rescue Ventolin HFA Use | over 12 weeks | Change from baseline in average daily rescue Ventolin HFA use over 12 weeks |
| Percentage of Subjects Achieving an MCID (Minimal Clinically Important Difference) of 4 Units or More in Saint George's Respiratory Questionnaire (SGRQ) Total Score | at Week 12 | The SGRQ (St. George's Respiratory Questionnaire) is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of BFF MDI on health-related quality of life as compared to FF MDI in subjects with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. A decrease from baseline in SGRQ total score of 4 units or more is considered a clinically meaningful improvement in quality of life. |
Countries
Argentina, Austria, Belgium, Brazil, Canada, Chile, Denmark, Germany, Italy, Mexico, Norway, Peru, Puerto Rico, Russia, South Africa, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
This study screened subjects at 292 study centers in 18 countries and randomized subjects at 259 study centers, from April 2016 to April 2018.
Pre-assignment details
Subjects were randomized in a 1:1:1 ratio to BFF MDI 320/9.6 μg, BFF MDI 160/9.6 μg, and FF MDI 9.6 μg treatment groups
Participants by arm
| Arm | Count |
|---|---|
| BFF MDI 320/9.6 ug Budesonide Formoterol Fumarate Metered dose inhalation 320/9.6 ug | 629 |
| BFF MDI 160/9.6 ug Budesonide Formoterol Fumarate Metered dose inhalation 160/9.6 ug | 630 |
| FF MDI 9.6 ug Formoterol Fumarate Metered dose inhalation 9.6 ug | 617 |
| Total | 1,876 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative Reasons | 2 | 3 | 4 |
| Overall Study | Adverse Event | 28 | 21 | 32 |
| Overall Study | Lack of Efficacy | 40 | 40 | 70 |
| Overall Study | Lost to Follow-up | 5 | 9 | 8 |
| Overall Study | Physician Decision | 3 | 8 | 14 |
| Overall Study | Protocol Specified Disc. Criteria | 5 | 5 | 2 |
| Overall Study | Protocol Violation | 7 | 5 | 5 |
| Overall Study | Withdrawal by Subject | 26 | 25 | 30 |
Baseline characteristics
| Characteristic | BFF MDI 320/9.6 ug | BFF MDI 160/9.6 ug | FF MDI 9.6 ug | Total |
|---|---|---|---|---|
| Age, Continuous | 65.3 Years STANDARD_DEVIATION 8.1 | 64.5 Years STANDARD_DEVIATION 8.4 | 64.8 Years STANDARD_DEVIATION 8.5 | 64.9 Years STANDARD_DEVIATION 8.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 190 Participants | 200 Participants | 190 Participants | 580 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 423 Participants | 414 Participants | 412 Participants | 1249 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 3 Participants | 5 Participants | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 26 Participants | 18 Participants | 24 Participants | 68 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 7 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 30 Participants | 22 Participants | 29 Participants | 81 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 47 Participants | 54 Participants | 46 Participants | 147 Participants |
| Race (NIH/OMB) White | 514 Participants | 516 Participants | 504 Participants | 1534 Participants |
| Sex: Female, Male Female | 252 Participants | 272 Participants | 268 Participants | 792 Participants |
| Sex: Female, Male Male | 367 Participants | 345 Participants | 339 Participants | 1051 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 619 | 4 / 617 | 8 / 607 |
| other Total, other adverse events | 266 / 619 | 279 / 617 | 268 / 607 |
| serious Total, serious adverse events | 60 / 619 | 78 / 617 | 83 / 607 |
Outcome results
Primary
Morning Pre-dose Trough FEV1
Morning pre-dose trough FEV1 (Forced Expiratory Volume in one second) at week 12
Time frame: at Week 12
Population: mITT Population Only subjects who had morning pre-dose trough FEV1 measured at the week 12 visit are included in the at Week 12 timepoint
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BFF MDI 320/9.6 ug | Morning Pre-dose Trough FEV1 | 0.072 Liter |
| BFF MDI 160/9.6 ug | Morning Pre-dose Trough FEV1 | 0.069 Liter |
| FF MDI 9.6 ug | Morning Pre-dose Trough FEV1 | 0.037 Liter |
Secondary
Change From Baseline in Average Daily Rescue Ventolin HFA Use
Change from baseline in average daily rescue Ventolin HFA use over 12 weeks
Time frame: over 12 weeks
Population: mITT Population Only subjects who had rescue Ventolin HFA doses recorded over the 12 week period are included in the over 12 Weeks timepoint
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BFF MDI 320/9.6 ug | Change From Baseline in Average Daily Rescue Ventolin HFA Use | -0.9 Puffs per day |
| BFF MDI 160/9.6 ug | Change From Baseline in Average Daily Rescue Ventolin HFA Use | -0.9 Puffs per day |
| FF MDI 9.6 ug | Change From Baseline in Average Daily Rescue Ventolin HFA Use | -0.6 Puffs per day |
Secondary
Percentage of Subjects Achieving an MCID (Minimal Clinically Important Difference) of 4 Units or More in Saint George's Respiratory Questionnaire (SGRQ) Total Score
The SGRQ (St. George's Respiratory Questionnaire) is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of BFF MDI on health-related quality of life as compared to FF MDI in subjects with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. A decrease from baseline in SGRQ total score of 4 units or more is considered a clinically meaningful improvement in quality of life.
Time frame: at Week 12
Population: mITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BFF MDI 320/9.6 ug | Percentage of Subjects Achieving an MCID (Minimal Clinically Important Difference) of 4 Units or More in Saint George's Respiratory Questionnaire (SGRQ) Total Score | 52 Percentage of Subjects |
| BFF MDI 160/9.6 ug | Percentage of Subjects Achieving an MCID (Minimal Clinically Important Difference) of 4 Units or More in Saint George's Respiratory Questionnaire (SGRQ) Total Score | 54 Percentage of Subjects |
| FF MDI 9.6 ug | Percentage of Subjects Achieving an MCID (Minimal Clinically Important Difference) of 4 Units or More in Saint George's Respiratory Questionnaire (SGRQ) Total Score | 44 Percentage of Subjects |
Secondary
Time to First Moderate or Severe COPD Exacerbation
Time to first moderate or severe COPD (Chronic Obstructive Pulmonary Disease) exacerbation over 52 weeks
Time frame: over 52 weeks
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BFF MDI 320/9.6 ug | Time to First Moderate or Severe COPD Exacerbation | Percent of Subjects Exacerbated within 12 Weeks | 19.2 Percentage of Subjects with Exacerbation |
| BFF MDI 320/9.6 ug | Time to First Moderate or Severe COPD Exacerbation | Percent of Subjects Exacerbated within 52 Weeks | 50.1 Percentage of Subjects with Exacerbation |
| BFF MDI 320/9.6 ug | Time to First Moderate or Severe COPD Exacerbation | Percent of Subjects Exacerbated within 24 Weeks | 31.2 Percentage of Subjects with Exacerbation |
| BFF MDI 320/9.6 ug | Time to First Moderate or Severe COPD Exacerbation | Percent of Subjects Exacerbated within 36 Weeks | 41.0 Percentage of Subjects with Exacerbation |
| BFF MDI 160/9.6 ug | Time to First Moderate or Severe COPD Exacerbation | Percent of Subjects Exacerbated within 12 Weeks | 19.3 Percentage of Subjects with Exacerbation |
| BFF MDI 160/9.6 ug | Time to First Moderate or Severe COPD Exacerbation | Percent of Subjects Exacerbated within 24 Weeks | 32.9 Percentage of Subjects with Exacerbation |
| BFF MDI 160/9.6 ug | Time to First Moderate or Severe COPD Exacerbation | Percent of Subjects Exacerbated within 36 Weeks | 41.3 Percentage of Subjects with Exacerbation |
| BFF MDI 160/9.6 ug | Time to First Moderate or Severe COPD Exacerbation | Percent of Subjects Exacerbated within 52 Weeks | 48.6 Percentage of Subjects with Exacerbation |
| FF MDI 9.6 ug | Time to First Moderate or Severe COPD Exacerbation | Percent of Subjects Exacerbated within 36 Weeks | 46.2 Percentage of Subjects with Exacerbation |
| FF MDI 9.6 ug | Time to First Moderate or Severe COPD Exacerbation | Percent of Subjects Exacerbated within 24 Weeks | 35.1 Percentage of Subjects with Exacerbation |
| FF MDI 9.6 ug | Time to First Moderate or Severe COPD Exacerbation | Percent of Subjects Exacerbated within 12 Weeks | 24.8 Percentage of Subjects with Exacerbation |
| FF MDI 9.6 ug | Time to First Moderate or Severe COPD Exacerbation | Percent of Subjects Exacerbated within 52 Weeks | 54.8 Percentage of Subjects with Exacerbation |