Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD
Brief summary
A chronic dosing (24 weeks) study to assess the efficacy and safety GFF MDI; PT003), FF MDI; PT005, and GP MDI; PT001) in subjects with moderate to very severe COPD, compared with placebo.
Detailed description
A randomized, double-blind, chronic dosing (24 weeks), placebo-controlled, parallel group, multi-center study to assess the efficacy and safety of glycopyrronium and formoterol fumarate inhalation aerosol (GFF; PT003), formoterol fumarate inhalation aerosol (FF; PT005), and glycopyrronium inhalation aerosol (GP; PT001) in subjects with moderate to very severe COPD, compared with placebo.
Interventions
DRUGGFF MDI (PT003)
Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI; PT003); Glycopyrronium and Formoterol Fumarate Inhalation Aerosol administered as 2 inhalations twice-daily (BID)
DRUGFF MDI (PT005)
Formoterol Fumarate Metered Dose Inhaler (FF MDI; PT005); Formoterol Fumarate Inhalation Aerosol administered as 2 inhalations twice-daily (BID)
DRUGGP MDI (PT001)
Glycopyrronium Metered Dose Inhaler (GP MDI; PT001); Glycopyrronium Inhalation Aerosol administered as 2 inhalations twice-daily (BID)
DRUGPlacebo MDI
Placebo (matching) for GFF MDI, FF MDI, and GP MDI administered as 2 inhalations twice-daily (BID)
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
* 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 serum pregnancy test at Visit 1, and agrees to acceptable contraceptive methods used consistently and correctly for the duration of the study. * 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. * Forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of \<0.70. * FEV1 must be \<80% predicted normal value calculated using the Third National Health and Nutrition Examination Survey (NHANES III) reference equations. (Or reference norms applicable to other regions).
Exclusion criteria
* Significant diseases other than COPD, ie, 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 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 Screening Period (Visit 1 to Visit 4). * 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 Screening Period (Visit 1 to Visit 4). * Subjects with a diagnosis of angle closure glaucoma will be excluded, regardless of whether or not they have been treated. Subjects with a diagnosis of open angle glaucoma who have intraocular pressure controlled with medication(s) are eligible. * 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 |
|---|---|---|
| Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 of Treatment (US/China Approach) | at week 24 | For the US/China approach, the primary endpoint was the change from baseline in morning pre-dose trough FEV1 at Week 24 of treatment |
| Change From Baseline in Morning Pre-dose Trough FEV1 Over Weeks 12-24, Japan Approach | over weeks 12-24 | Change from baseline in morning pre-dose trough FEV1 over weeks 12-24, Japan approach |
| Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks. Primary Endpoint, EU/SK/TW Approach, Secondary Endpoint US/China Approach. | over 24 weeks | Change from baseline in morning pre-dose trough FEV1 over 24 weeks. Primary endpoint, EU/SK/TW approach, Secondary endpoint US/China approach. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TDI Focal Score Over Weeks 12-24 - Japan Approach - Symptomatic Population | over weeks 12-24 | TDI focal score over 12-24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9 |
| Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing at Week 24 US/China Approach | at week 24 | Peak change from baseline in FEV1 within 2 hours post-dosing at Week 24 US/China approach |
| Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over Weeks 12-24 Japan Approach | over weeks 12-24 | Peak change from baseline in FEV1 within 2 hours post-dosing over weeks 12-24 Japan approach |
| Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over 24 Weeks EU/SK/TW Approach | over 24 weeks | Peak change from baseline in FEV1 within 2 hours post-dosing over 24 weeks EU/SK/TW approach |
| Change From Baseline in SGRQ Total Score at Week 24, US/China Approach | at week 24 | Change from baseline in the SGRQ total score. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI on health-related quality of life as compared to placebo 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. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life |
| TDI Focal Score Over 24 Weeks, US/China and EU/SK/TW Approach | over 24 Weeks | TDI focal score over 24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9 |
| Change From Baseline in SGRQ Total Score at Week 24 in Symptomatic Population, US/China Approach | at week 24 | Change from baseline in the SGRQ total score. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI on health-related quality of life as compared to placebo 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. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life |
| Change From Baseline in SGRQ Total Score Over Weeks 12-24, in Symptomatic Population, Japan & EU/SK/TW Approach | over weeks 12-24 | Change from baseline in the SGRQ total score. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI on health-related quality of life as compared to placebo 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. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life |
| Change From Baseline in Average Daily Rescue Ventolin Use Over 24 Weeks in RVU Population, All Approaches | over 24 weeks | Change from baseline in average daily rescue Ventolin use over 24 weeks in RVU population, all approaches |
| FEV1 Measured at 5 Minutes Post-dose on Day 1 | Assessed at 5-minutes post dose on Day 1 | Onset of Action as Assessed by FEV1 Day 1 at 5 Minutes Post-Dose. Reported is the FEV1 measured at 5 minutes post-dose on Day 1 as the first time point when the difference from Placebo was statistically significant |
| FEV1 Measured at 15 Minutes Post-dose on Day 1 | Assessed at 15-minute post dose on Day 1 | Onset of Action as Assessed by FEV1 Day 1 at 15 Minutes Post-Dose. Reported is the FEV1 measured at 15 minutes post-dose on Day 1 as the first time point when the difference from Placebo was statistically significant |
| Change From Baseline in SGRQ Total Score Over Weeks 12-24 , Japan & EU/SK/TW Approach | over weeks 12-24 | Change from baseline in the SGRQ total score. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI on health-related quality of life as compared to placebo 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. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life |
| TDI Focal Score Over Weeks 12-24 Japan Approach | over Weeks 12-24 | TDI focal score over 12-24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9 |
| TDI Focal Score Over 24 Weeks - US/China and EU/SK/TW Approaches -Symptomatic Population | over 24 Weeks | TDI focal score over 24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9 |
Countries
China, Czechia, Germany, Hungary, Japan, Poland, Russia, South Korea, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 175 sites in the United States, United Kingdom, Taiwan (TW),South Korea (SK), Russia, Poland, Hungary, Germany, Czech Republic, China, and Japan from April 2015 to August 2017. The entire study period was scheduled to take approximately 30 weeks for each individual subject from the time of screening.
Pre-assignment details
Subjects were randomized in a 7:6:6:3 scheme (GFF MDI, FF MDI, GP MDI, and Placebo MDI). Randomization was stratified by reversibility to Ventolin HFA and COPD disease severity (moderate vs severe or very severe) to ensure a similar distribution of treatment arms across stratum.
Participants by arm
| Arm | Count |
|---|---|
| GFF MDI 14.4/9.6 ug Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug | 551 |
| FF MDI 9.6 ug Formoterol Fumarate, Metered Dose Inhalation 9.6 ug | 480 |
| GP MDI 14.4 ug Glycopyrronium 14.4 ug Metered Dose Inhalation | 474 |
| Placebo MDI Placebo Metered Dose Inhalation | 235 |
| Total | 1,740 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 15 | 14 | 15 | 3 |
| Overall Study | Lack of Efficacy | 3 | 8 | 4 | 8 |
| Overall Study | Lost to Follow-up | 5 | 5 | 3 | 1 |
| Overall Study | Physician Decision | 1 | 4 | 2 | 2 |
| Overall Study | Protocol Specified Criteria | 17 | 13 | 14 | 8 |
| Overall Study | Protocol Violation | 2 | 5 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 18 | 17 | 23 | 14 |
Baseline characteristics
| Characteristic | GFF MDI 14.4/9.6 ug | Total | Placebo MDI | GP MDI 14.4 ug | FF MDI 9.6 ug |
|---|---|---|---|---|---|
| Age, Continuous | 64.7 Years STANDARD_DEVIATION 7.4 | 64.2 Years STANDARD_DEVIATION 7.7 | 63.9 Years STANDARD_DEVIATION 7.5 | 64.0 Years STANDARD_DEVIATION 8.1 | 64.1 Years STANDARD_DEVIATION 7.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 223 Participants | 700 Participants | 92 Participants | 181 Participants | 204 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 52 Participants | 6 Participants | 18 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 315 Participants | 987 Participants | 137 Participants | 275 Participants | 260 Participants |
| Sex: Female, Male Female | 143 Participants | 450 Participants | 64 Participants | 128 Participants | 115 Participants |
| Sex: Female, Male Male | 408 Participants | 1290 Participants | 171 Participants | 346 Participants | 365 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 551 | 1 / 480 | 1 / 474 | 1 / 235 |
| other Total, other adverse events | 166 / 551 | 123 / 480 | 128 / 474 | 61 / 235 |
| serious Total, serious adverse events | 53 / 551 | 40 / 480 | 34 / 474 | 19 / 235 |
Outcome results
Primary
Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 of Treatment (US/China Approach)
For the US/China approach, the primary endpoint was the change from baseline in morning pre-dose trough FEV1 at Week 24 of treatment
Time frame: at week 24
Population: ITT Population - defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects were analyzed according to the treatment they were assigned to at randomization. Number of participants analyzed reflects the ITT population with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 of Treatment (US/China Approach) | 120 mL |
| FF MDI 9.6 ug | Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 of Treatment (US/China Approach) | 47 mL |
| GP MDI 14.4 ug | Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 of Treatment (US/China Approach) | 60 mL |
| Placebo MDI | Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 of Treatment (US/China Approach) | -45 mL |
Primary
Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks. Primary Endpoint, EU/SK/TW Approach, Secondary Endpoint US/China Approach.
Change from baseline in morning pre-dose trough FEV1 over 24 weeks. Primary endpoint, EU/SK/TW approach, Secondary endpoint US/China approach.
Time frame: over 24 weeks
Population: ITT Population - defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects were analyzed according to the treatment they were assigned to at randomization. Number of participants analyzed reflects the ITT population with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks. Primary Endpoint, EU/SK/TW Approach, Secondary Endpoint US/China Approach. | 135 mL |
| FF MDI 9.6 ug | Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks. Primary Endpoint, EU/SK/TW Approach, Secondary Endpoint US/China Approach. | 63 mL |
| GP MDI 14.4 ug | Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks. Primary Endpoint, EU/SK/TW Approach, Secondary Endpoint US/China Approach. | 80 mL |
| Placebo MDI | Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks. Primary Endpoint, EU/SK/TW Approach, Secondary Endpoint US/China Approach. | -20 mL |
Primary
Change From Baseline in Morning Pre-dose Trough FEV1 Over Weeks 12-24, Japan Approach
Change from baseline in morning pre-dose trough FEV1 over weeks 12-24, Japan approach
Time frame: over weeks 12-24
Population: ITT Population - defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects were analyzed according to the treatment they were assigned to at randomization. Number of participants analyzed reflects the ITT population with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | Change From Baseline in Morning Pre-dose Trough FEV1 Over Weeks 12-24, Japan Approach | 128 mL |
| FF MDI 9.6 ug | Change From Baseline in Morning Pre-dose Trough FEV1 Over Weeks 12-24, Japan Approach | 54 mL |
| GP MDI 14.4 ug | Change From Baseline in Morning Pre-dose Trough FEV1 Over Weeks 12-24, Japan Approach | 74 mL |
| Placebo MDI | Change From Baseline in Morning Pre-dose Trough FEV1 Over Weeks 12-24, Japan Approach | -25 mL |
Secondary
Change From Baseline in Average Daily Rescue Ventolin Use Over 24 Weeks in RVU Population, All Approaches
Change from baseline in average daily rescue Ventolin use over 24 weeks in RVU population, all approaches
Time frame: over 24 weeks
Population: RVU Population - defined as Rescue Ventolin User
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | Change From Baseline in Average Daily Rescue Ventolin Use Over 24 Weeks in RVU Population, All Approaches | -1.4 Puffs/day |
| FF MDI 9.6 ug | Change From Baseline in Average Daily Rescue Ventolin Use Over 24 Weeks in RVU Population, All Approaches | -1.0 Puffs/day |
| GP MDI 14.4 ug | Change From Baseline in Average Daily Rescue Ventolin Use Over 24 Weeks in RVU Population, All Approaches | -0.6 Puffs/day |
| Placebo MDI | Change From Baseline in Average Daily Rescue Ventolin Use Over 24 Weeks in RVU Population, All Approaches | -0.4 Puffs/day |
Secondary
Change From Baseline in SGRQ Total Score at Week 24 in Symptomatic Population, US/China Approach
Change from baseline in the SGRQ total score. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI on health-related quality of life as compared to placebo 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. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life
Time frame: at week 24
Population: Symptomatic Population was defined as all subjects in the ITT Population with CAT scores of ≥15 at Visit 2n
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | Change From Baseline in SGRQ Total Score at Week 24 in Symptomatic Population, US/China Approach | -6.9 Scores on a scale |
| FF MDI 9.6 ug | Change From Baseline in SGRQ Total Score at Week 24 in Symptomatic Population, US/China Approach | -7.8 Scores on a scale |
| GP MDI 14.4 ug | Change From Baseline in SGRQ Total Score at Week 24 in Symptomatic Population, US/China Approach | -3.8 Scores on a scale |
| Placebo MDI | Change From Baseline in SGRQ Total Score at Week 24 in Symptomatic Population, US/China Approach | -1.6 Scores on a scale |
Secondary
Change From Baseline in SGRQ Total Score at Week 24, US/China Approach
Change from baseline in the SGRQ total score. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI on health-related quality of life as compared to placebo 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. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life
Time frame: at week 24
Population: ITT Population - defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects were analyzed according to the treatment they were assigned to at randomization. Number of participants analyzed reflects the ITT population with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | Change From Baseline in SGRQ Total Score at Week 24, US/China Approach | -5.3 Scores on a scale |
| FF MDI 9.6 ug | Change From Baseline in SGRQ Total Score at Week 24, US/China Approach | -5.6 Scores on a scale |
| GP MDI 14.4 ug | Change From Baseline in SGRQ Total Score at Week 24, US/China Approach | -3.7 Scores on a scale |
| Placebo MDI | Change From Baseline in SGRQ Total Score at Week 24, US/China Approach | -0.9 Scores on a scale |
Secondary
Change From Baseline in SGRQ Total Score Over Weeks 12-24, in Symptomatic Population, Japan & EU/SK/TW Approach
Change from baseline in the SGRQ total score. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI on health-related quality of life as compared to placebo 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. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life
Time frame: over weeks 12-24
Population: Symptomatic Population was defined as all subjects in the ITT Population with CAT scores of ≥15 at Visit 2
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | Change From Baseline in SGRQ Total Score Over Weeks 12-24, in Symptomatic Population, Japan & EU/SK/TW Approach | -6.9 Scores on a scale |
| FF MDI 9.6 ug | Change From Baseline in SGRQ Total Score Over Weeks 12-24, in Symptomatic Population, Japan & EU/SK/TW Approach | -7.3 Scores on a scale |
| GP MDI 14.4 ug | Change From Baseline in SGRQ Total Score Over Weeks 12-24, in Symptomatic Population, Japan & EU/SK/TW Approach | -3.9 Scores on a scale |
| Placebo MDI | Change From Baseline in SGRQ Total Score Over Weeks 12-24, in Symptomatic Population, Japan & EU/SK/TW Approach | -3.1 Scores on a scale |
Secondary
Change From Baseline in SGRQ Total Score Over Weeks 12-24 , Japan & EU/SK/TW Approach
Change from baseline in the SGRQ total score. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI on health-related quality of life as compared to placebo 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. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life
Time frame: over weeks 12-24
Population: ITT Population - defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects were analyzed according to the treatment they were assigned to at randomization. Number of participants analyzed reflects the ITT population with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | Change From Baseline in SGRQ Total Score Over Weeks 12-24 , Japan & EU/SK/TW Approach | -5.2 Scores on a scale |
| FF MDI 9.6 ug | Change From Baseline in SGRQ Total Score Over Weeks 12-24 , Japan & EU/SK/TW Approach | -5.0 Scores on a scale |
| GP MDI 14.4 ug | Change From Baseline in SGRQ Total Score Over Weeks 12-24 , Japan & EU/SK/TW Approach | -3.6 Scores on a scale |
| Placebo MDI | Change From Baseline in SGRQ Total Score Over Weeks 12-24 , Japan & EU/SK/TW Approach | -1.7 Scores on a scale |
Secondary
FEV1 Measured at 15 Minutes Post-dose on Day 1
Onset of Action as Assessed by FEV1 Day 1 at 15 Minutes Post-Dose. Reported is the FEV1 measured at 15 minutes post-dose on Day 1 as the first time point when the difference from Placebo was statistically significant
Time frame: Assessed at 15-minute post dose on Day 1
Population: ITT Population - defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects were analyzed according to the treatment they were assigned to at randomization. Number of participants analyzed reflects the ITT population with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | FEV1 Measured at 15 Minutes Post-dose on Day 1 | 0.241 Liters |
| FF MDI 9.6 ug | FEV1 Measured at 15 Minutes Post-dose on Day 1 | 0.220 Liters |
| GP MDI 14.4 ug | FEV1 Measured at 15 Minutes Post-dose on Day 1 | 0.105 Liters |
| Placebo MDI | FEV1 Measured at 15 Minutes Post-dose on Day 1 | 0.033 Liters |
Secondary
FEV1 Measured at 5 Minutes Post-dose on Day 1
Onset of Action as Assessed by FEV1 Day 1 at 5 Minutes Post-Dose. Reported is the FEV1 measured at 5 minutes post-dose on Day 1 as the first time point when the difference from Placebo was statistically significant
Time frame: Assessed at 5-minutes post dose on Day 1
Population: ITT Population - defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects were analyzed according to the treatment they were assigned to at randomization. Number of participants analyzed reflects the ITT population with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | FEV1 Measured at 5 Minutes Post-dose on Day 1 | 0.202 Liters |
| FF MDI 9.6 ug | FEV1 Measured at 5 Minutes Post-dose on Day 1 | 0.186 Liters |
| GP MDI 14.4 ug | FEV1 Measured at 5 Minutes Post-dose on Day 1 | 0.059 Liters |
| Placebo MDI | FEV1 Measured at 5 Minutes Post-dose on Day 1 | 0.022 Liters |
Secondary
Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing at Week 24 US/China Approach
Peak change from baseline in FEV1 within 2 hours post-dosing at Week 24 US/China approach
Time frame: at week 24
Population: ITT Population - defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects were analyzed according to the treatment they were assigned to at randomization. Number of participants analyzed reflects the ITT population with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing at Week 24 US/China Approach | 358 mL |
| FF MDI 9.6 ug | Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing at Week 24 US/China Approach | 247 mL |
| GP MDI 14.4 ug | Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing at Week 24 US/China Approach | 214 mL |
| Placebo MDI | Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing at Week 24 US/China Approach | 55 mL |
Secondary
Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over 24 Weeks EU/SK/TW Approach
Peak change from baseline in FEV1 within 2 hours post-dosing over 24 weeks EU/SK/TW approach
Time frame: over 24 weeks
Population: ITT Population - defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects were analyzed according to the treatment they were assigned to at randomization. Number of participants analyzed reflects the ITT population with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over 24 Weeks EU/SK/TW Approach | 375 mL |
| FF MDI 9.6 ug | Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over 24 Weeks EU/SK/TW Approach | 277 mL |
| GP MDI 14.4 ug | Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over 24 Weeks EU/SK/TW Approach | 234 mL |
| Placebo MDI | Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over 24 Weeks EU/SK/TW Approach | 82 mL |
Secondary
Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over Weeks 12-24 Japan Approach
Peak change from baseline in FEV1 within 2 hours post-dosing over weeks 12-24 Japan approach
Time frame: over weeks 12-24
Population: ITT Population - defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects were analyzed according to the treatment they were assigned to at randomization. Number of participants analyzed reflects the ITT population with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over Weeks 12-24 Japan Approach | 368 mL |
| FF MDI 9.6 ug | Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over Weeks 12-24 Japan Approach | 255 mL |
| GP MDI 14.4 ug | Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over Weeks 12-24 Japan Approach | 228 mL |
| Placebo MDI | Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over Weeks 12-24 Japan Approach | 70 mL |
Secondary
TDI Focal Score Over 24 Weeks, US/China and EU/SK/TW Approach
TDI focal score over 24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9
Time frame: over 24 Weeks
Population: ITT Population - defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects were analyzed according to the treatment they were assigned to at randomization. Number of participants analyzed reflects the ITT population with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | TDI Focal Score Over 24 Weeks, US/China and EU/SK/TW Approach | 1.6 Scores on a scale |
| FF MDI 9.6 ug | TDI Focal Score Over 24 Weeks, US/China and EU/SK/TW Approach | 1.5 Scores on a scale |
| GP MDI 14.4 ug | TDI Focal Score Over 24 Weeks, US/China and EU/SK/TW Approach | 1.3 Scores on a scale |
| Placebo MDI | TDI Focal Score Over 24 Weeks, US/China and EU/SK/TW Approach | 0.8 Scores on a scale |
Secondary
TDI Focal Score Over 24 Weeks - US/China and EU/SK/TW Approaches -Symptomatic Population
TDI focal score over 24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9
Time frame: over 24 Weeks
Population: Symptomatic Population was defined as all subjects in the ITT Population with CAT scores of ≥15 at Visit 2
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | TDI Focal Score Over 24 Weeks - US/China and EU/SK/TW Approaches -Symptomatic Population | 1.5 Scores on a scale |
| FF MDI 9.6 ug | TDI Focal Score Over 24 Weeks - US/China and EU/SK/TW Approaches -Symptomatic Population | 1.3 Scores on a scale |
| GP MDI 14.4 ug | TDI Focal Score Over 24 Weeks - US/China and EU/SK/TW Approaches -Symptomatic Population | 1.1 Scores on a scale |
| Placebo MDI | TDI Focal Score Over 24 Weeks - US/China and EU/SK/TW Approaches -Symptomatic Population | 0.7 Scores on a scale |
Secondary
TDI Focal Score Over Weeks 12-24 Japan Approach
TDI focal score over 12-24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9
Time frame: over Weeks 12-24
Population: ITT Population - defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects were analyzed according to the treatment they were assigned to at randomization. Number of participants analyzed reflects the ITT population with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | TDI Focal Score Over Weeks 12-24 Japan Approach | 1.7 Scores on a scale |
| FF MDI 9.6 ug | TDI Focal Score Over Weeks 12-24 Japan Approach | 1.5 Scores on a scale |
| GP MDI 14.4 ug | TDI Focal Score Over Weeks 12-24 Japan Approach | 1.4 Scores on a scale |
| Placebo MDI | TDI Focal Score Over Weeks 12-24 Japan Approach | 0.8 Scores on a scale |
Secondary
TDI Focal Score Over Weeks 12-24 - Japan Approach - Symptomatic Population
TDI focal score over 12-24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9
Time frame: over weeks 12-24
Population: Symptomatic Population was defined as all subjects in the ITT Population with CAT scores of ≥15 at Visit 2
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI 14.4/9.6 ug | TDI Focal Score Over Weeks 12-24 - Japan Approach - Symptomatic Population | 1.5 Scores on a scale |
| FF MDI 9.6 ug | TDI Focal Score Over Weeks 12-24 - Japan Approach - Symptomatic Population | 1.4 Scores on a scale |
| GP MDI 14.4 ug | TDI Focal Score Over Weeks 12-24 - Japan Approach - Symptomatic Population | 1.1 Scores on a scale |
| Placebo MDI | TDI Focal Score Over Weeks 12-24 - Japan Approach - Symptomatic Population | 0.7 Scores on a scale |