Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Brief summary
This is a randomized, placebo-controlled, parallel-group, multi-site, double-blind study evaluating the efficacy of mometasone furoate/formoterol fumarate (MF/F) metered dose inhaler (MDI) 400/10 mcg twice daily (BID) and MF/F MDI 200/10 mcg BID compared with MF 400 mcg BID and F 10 mcg BID in adults at least 40 years of age, with moderate to severe chronic obstructive pulmonary disease (COPD). All placebo-treated subjects and active-treated subjects who will not participate in the safety extension will be discontinued and will have their Final Visit at Week 26. Subjects who continue into the 26-week safety extension will have their Final Visit at Week 52. Efficacy will be measured by the mean change from Baseline to Week 13 in area under the forced expiratory volume in one second concentration time curve from 0 to 12 hours (FEV1 AUC\[0-12hr\]) and change from Baseline to Week 13 in AM predose FEV1.
Interventions
MF/F 400/10 mcg via a metered dose inhaler (MDI) twice daily for 52 weeks
MF 400 mcg via metered dose inhaler twice daily for 52 weeks
DRUGFormoterol MDI
Formoterol 10 mcg via metered dose inhaler twice a day for 52 weeks
DRUGPlacebo
Placebo MDI twice a day for 26 weeks
Sponsors
Novartis
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Moderate to severe COPD based on prebronchodilator FEV1/forced vital capacity (FVC) ratio of \<=70%. * At Screening & Baseline, postbronchodilator FEV1 must be \>= 60% predicted normal & \>=25% predicted normal. * COPD symptoms for \>=24 months. * \>=2 COPD exacerbations requiring course of oral corticosteroid &/or antibiotics within 2-12 months before screening. * Ex- or current smoker with smoking history \>=10 pack years. * Only albuterol/salbutamol for relief for at least 2 weeks prior to randomization. * Withdraw from parenteral & oral steroids, anticholinergics, & antibiotics 4 weeks prior to Screening. * No harm in changing current COPD therapy, willing to discontinue his/her anticholinergics, inhaled corticosteroids (ICS) or ICS/long-acting beta agonists (LABA) at Screening, & transferred to albuterol/salbutamol for relief for 2 weeks prior to Randomization. * Lab tests conducted at Screening must be acceptable to investigator. Electrocardiogram (ECG) performed at Screening or within 30 days prior to Screening must be acceptable to investigator. Chest X-ray or computerized tomography (CT) scan is acceptable within 12 months prior to Screening must be acceptable to investigator. * Female of childbearing potential must use birth control. Includes: hormonal contraceptives, intra-uterine device (IUD), condom in combination with spermicide, monogamous relationship with male partner who had vasectomy. Started birth control at least 3 months prior to Screening (exception condom), & must agree to continue. Female who is not currently sexually active must agree/consent to using a method should she become sexually active. Women who have been surgically sterilized or are at least 1 year postmenopausal are not considered to be of childbearing potential. Female must have negative serum pregnancy test at Screening.
Exclusion criteria
* Evidence (upon visual inspection) of oropharyngeal candidiasis at Baseline with or without treatment. If there is evidence at Screening, may be treated as appropriate & visit can be scheduled upon resolution. If there is evidence at Baseline, may be treated as appropriate & visit can be rescheduled upon resolution. * History of renal, hepatic, cardiovascular, metabolic, neurologic, hematologic, ophthalmological, respiratory, gastrointestinal, cerebrovascular, or other which could interfere with study or require treatment which might interfere with study. Examples include (but are not limited to) hypertension treated with beta-blockers), active hepatitis, coronary artery disease, arrhythmia, significant QTc prolongation (ie QTcF or QTcB \[Fridericia or Bazett corrections, respectively \>500 milliseconds (msecs)\]) stroke, severe rheumatoid arthritis, chronic open-angle glaucoma or posterior subcapsular cataracts, acquired immune deficiency syndrome (AIDS), or conditions that may interfere with respiratory function such as asthma, bronchiectasis, cystic fibrosis. Others which are well-controlled & stable (eg hypertension not requiring beta-blockers) will not prohibit participation if appropriate to investigator. * Allergy/sensitivity to glucocorticosteroids, beta-2 agonists, study drug/excipients. * Female who is breast-feeding, pregnant, or intends to become pregnant. * Illicit drug user. * Human immunodeficiency virus (HIV) positive (testing not conducted). * Unable to correctly use oral MDI. * Taking any restricted medications prior to Screening without meeting washout. * Cannot adhere to permitted concomitant & prohibited medications. * May not participate in this same study at another investigational site. Cannot participate in different investigational study at any site, during same time. * Not be randomized into study more than once. * No person directly associated with administration of study may participate. * Previously participated in MF/F trial. * Increase in absolute volume of \>=400 milliliters (mL) at Screening or prior to Baseline within 30 minutes after administration of 4 inhalations of albuterol/salbutamol (total dose of 360 to 400 mcg), or nebulized 2.5 mg albuterol/salbutamol. * Asthma. * Lobectomy, pneumonectomy or lung volume reduction surgery. * Lung cancer. * Requires long-term administration of oxygen (\>15 hours/day). * Alpha-1-antitrypsin deficiency. * A history and/or presence of intraocular pressure in either eye \>=22 millimeters of mercury (mm Hg), glaucoma, and/or posterior subcapsular cataracts. A subject who has undergone incisional or intraocular surgery in which the natural lens is still present in the eye. A subject with a history of penetrating trauma to both eyes. A subject with one or more of the following Lens Opacities Classification System (LOCS) III grades at screening: * nuclear opalescence (NO): \>=3.0, * nuclear color (NC): \>=3.0, * cortical cataract (C): \>=2.0, * posterior subcapsular (P): \>=0.5.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 13 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Baseline to Endpoint (13 weeks) | FEV1 AUC was standardized to liters. Endpoint was the last post-baseline non-missing result through Week 13 carried forward. |
| Mean Change From Baseline to Week 13 Endpoint in AM Predose FEV1 | Baseline to Endpoint (13 weeks) | Endpoint was the last post-baseline non-missing result through Week 13 carried forward. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Mild, Moderate, or Severe COPD Exacerbations | Endpoint (26 weeks) | Mild = 12 or more inhalations/day of inhaled rescue medication or 2 or more nebulized treatments/day of inhaled rescue medication. Moderate = treatment with antibiotics or oral steroids. Severe = emergency room treatment or hospitalizations of survival curves. If an event was composed of multiple criteria, the most severe criteria was assigned to the event. |
| Change From Baseline to Endpoint in St George's Respiratory Questionaire (SGRQ) Total Score | Baseline to Endpoint (26 weeks) | SGRQ consisted of 76 items aggregated into 3 component scores: symptoms (frequency/severity), activity (cause or limited by breathlessness), impact (social functioning, psychological disturbances from airway disease), & total score. Best health scores have a low numeric value. All component scores & total score ranged from 0-100, with a higher score indicating greater disease burden. A 4-point increase over placebo (and Baseline) was considered the minimum clinically important difference. Endpoint was the last post-baseline non-missing result through the 26 week evaluation carried forward. |
| Change From Baseline in Proportion of Chronic Obstructive Pulmonary Disease (COPD) Symptom-Free Nights (AM Diary Symptoms) | Baseline to Endpoint (26 weeks) | Prior to the use of study drug rescue medication (in the morning upon awakening) the participant evaluated the COPD symptoms of wheezing, cough, and difficulty breathing. A symptom-free night was defined as a combined score of 0 (no symptoms) across all three COPD symptoms evaluated the following morning. Proportion for Baseline included data from the last week before the first dose. Proportion for Endpoint included data across the entire 26-week treatment period. |
| Number of Participants With Partly Stable COPD | Endpoint (26 weeks) | Partly stable COPD was a composite measure that included the following COPD outcomes: (1) No oral steroid rescue medication; (2) No AM or PM COPD weekly average symptom score greater than 2 during at least 7 of 8 weeks; (3) No moderate or severe exacerbations; (4) No unscheduled visits due to COPD worsenings; (5) No study discontinuation due to treatment failure or treatment-related adverse event as determined by the investigator. |
Participant flow
Pre-assignment details
At Week 26, all participants randomized to placebo were to be discontinued, while 75% of participants randomized to an active treatment were randomly selected to participate in the 26-week Treatment Safety Extension. Several placebo-treated participants continued in error into the Treatment Safety Extension.
Participants by arm
| Arm | Count |
|---|---|
| MF/F MDI 400/10 mcg BID Mometasone furoate/formoterol fumarate (MF/F) 400/10 mcg via a metered dose inhaler (MDI) twice daily (BID) for 52 weeks. | 225 |
| MF/F MDI 200/10 mcg BID MF/F 200/10 mcg via a MDI BID for 52 weeks. | 239 |
| MF MDI 400 mcg BID Mometasone furoate (MF) 400 mcg via a MDI BID for 52 weeks. | 253 |
| F MDI 10 mcg BID Formoterol fumarate (F) 10 mcg via a MDI BID for 52 weeks. | 243 |
| Placebo Placebo MDI BID for 26 weeks. | 236 |
| Total | 1,196 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| 26-Week Double-Blind Treatment Period | Administrative | 1 | 3 | 3 | 3 | 3 |
| 26-Week Double-Blind Treatment Period | Adverse Event | 11 | 5 | 7 | 14 | 13 |
| 26-Week Double-Blind Treatment Period | Did not meet protocol eligibility | 5 | 6 | 11 | 4 | 13 |
| 26-Week Double-Blind Treatment Period | Lack of Efficacy | 1 | 3 | 3 | 4 | 8 |
| 26-Week Double-Blind Treatment Period | Lost to Follow-up | 0 | 0 | 2 | 1 | 4 |
| 26-Week Double-Blind Treatment Period | Non-compliance with protocol | 7 | 5 | 4 | 6 | 6 |
| 26-Week Double-Blind Treatment Period | Ongoing | 1 | 0 | 0 | 0 | 0 |
| 26-Week Double-Blind Treatment Period | Participant withdrawal related | 5 | 3 | 6 | 8 | 9 |
| 26-Week Double-Blind Treatment Period | Participant withdrawal unrelated | 4 | 12 | 15 | 10 | 11 |
| 26-Week Treatment Safety Extension | Administrative | 1 | 2 | 3 | 1 | 0 |
| 26-Week Treatment Safety Extension | Adverse Event | 6 | 7 | 10 | 1 | 0 |
| 26-Week Treatment Safety Extension | Did not meet protocol eligibility | 1 | 0 | 1 | 1 | 0 |
| 26-Week Treatment Safety Extension | Lack of Efficacy | 0 | 2 | 4 | 1 | 0 |
| 26-Week Treatment Safety Extension | Lost to Follow-up | 2 | 0 | 1 | 1 | 0 |
| 26-Week Treatment Safety Extension | Non-compliance with protocol | 2 | 1 | 1 | 4 | 0 |
| 26-Week Treatment Safety Extension | Participant withdrawal related | 1 | 1 | 1 | 1 | 0 |
| 26-Week Treatment Safety Extension | Participant withdrawal unrelated | 6 | 4 | 2 | 7 | 0 |
Baseline characteristics
| Characteristic | MF MDI 400 mcg BID | MF/F MDI 400/10 mcg BID | MF/F MDI 200/10 mcg BID | F MDI 10 mcg BID | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 60.5 years STANDARD_DEVIATION 8.5 | 59.2 years STANDARD_DEVIATION 9.1 | 60.1 years STANDARD_DEVIATION 9 | 59.7 years STANDARD_DEVIATION 8.7 | 58.8 years STANDARD_DEVIATION 9.5 | 59.7 years STANDARD_DEVIATION 9 |
| Sex: Female, Male Female | 56 Participants | 57 Participants | 64 Participants | 61 Participants | 58 Participants | 296 Participants |
| Sex: Female, Male Male | 197 Participants | 168 Participants | 175 Participants | 182 Participants | 178 Participants | 900 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 37 / 225 | 28 / 239 | 34 / 253 | 30 / 243 | 34 / 236 |
| serious Total, serious adverse events | 26 / 225 | 28 / 239 | 33 / 253 | 25 / 243 | 21 / 236 |
Outcome results
Primary
Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 13 in Forced Expiratory Volume (Liters) in 1 Second (FEV1)
FEV1 AUC was standardized to liters. Endpoint was the last post-baseline non-missing result through Week 13 carried forward.
Time frame: Baseline to Endpoint (13 weeks)
Population: Intent-to-treat (ITT) population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI 400/10 mcg BID | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 13 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Baseline | 1.189 Liters | Standard Deviation 0.408 |
| MF/F MDI 400/10 mcg BID | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 13 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Endpoint (Change from Baseline) | 0.179 Liters | Standard Deviation 0.274 |
| MF/F MDI 200/10 mcg BID | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 13 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Baseline | 1.195 Liters | Standard Deviation 0.408 |
| MF/F MDI 200/10 mcg BID | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 13 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Endpoint (Change from Baseline) | 0.139 Liters | Standard Deviation 0.274 |
| MF MDI 400 mcg BID | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 13 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Baseline | 1.260 Liters | Standard Deviation 0.408 |
| MF MDI 400 mcg BID | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 13 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Endpoint (Change from Baseline) | 0.053 Liters | Standard Deviation 0.274 |
| F MDI 10 mcg BID | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 13 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Endpoint (Change from Baseline) | 0.092 Liters | Standard Deviation 0.274 |
| F MDI 10 mcg BID | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 13 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Baseline | 1.176 Liters | Standard Deviation 0.408 |
| Placebo | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 13 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Baseline | 1.205 Liters | Standard Deviation 0.408 |
| Placebo | Mean Area Under the Time Curve From 0 to 12 Hours (AUC(0-12 Hours)) of Change From Baseline to Week 13 in Forced Expiratory Volume (Liters) in 1 Second (FEV1) | Endpoint (Change from Baseline) | 0.018 Liters | Standard Deviation 0.274 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Primary
Mean Change From Baseline to Week 13 Endpoint in AM Predose FEV1
Endpoint was the last post-baseline non-missing result through Week 13 carried forward.
Time frame: Baseline to Endpoint (13 weeks)
Population: ITT population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI 400/10 mcg BID | Mean Change From Baseline to Week 13 Endpoint in AM Predose FEV1 | Endpoint (Change from Baseline) | 0.098 Liters | Standard Deviation 0.28 |
| MF/F MDI 400/10 mcg BID | Mean Change From Baseline to Week 13 Endpoint in AM Predose FEV1 | Baseline | 1.188 Liters | Standard Deviation 0.408 |
| MF/F MDI 200/10 mcg BID | Mean Change From Baseline to Week 13 Endpoint in AM Predose FEV1 | Endpoint (Change from Baseline) | 0.063 Liters | Standard Deviation 0.28 |
| MF/F MDI 200/10 mcg BID | Mean Change From Baseline to Week 13 Endpoint in AM Predose FEV1 | Baseline | 1.194 Liters | Standard Deviation 0.408 |
| MF MDI 400 mcg BID | Mean Change From Baseline to Week 13 Endpoint in AM Predose FEV1 | Baseline | 1.255 Liters | Standard Deviation 0.408 |
| MF MDI 400 mcg BID | Mean Change From Baseline to Week 13 Endpoint in AM Predose FEV1 | Endpoint (Change from Baseline) | 0.028 Liters | Standard Deviation 0.28 |
| F MDI 10 mcg BID | Mean Change From Baseline to Week 13 Endpoint in AM Predose FEV1 | Baseline | 1.175 Liters | Standard Deviation 0.408 |
| F MDI 10 mcg BID | Mean Change From Baseline to Week 13 Endpoint in AM Predose FEV1 | Endpoint (Change from Baseline) | 0.049 Liters | Standard Deviation 0.28 |
| Placebo | Mean Change From Baseline to Week 13 Endpoint in AM Predose FEV1 | Endpoint (Change from Baseline) | -0.003 Liters | Standard Deviation 0.28 |
| Placebo | Mean Change From Baseline to Week 13 Endpoint in AM Predose FEV1 | Baseline | 1.205 Liters | Standard Deviation 0.408 |
p-value: 0.062ANCOVA
p-value: 0.583ANCOVA
Secondary
Change From Baseline in Proportion of Chronic Obstructive Pulmonary Disease (COPD) Symptom-Free Nights (AM Diary Symptoms)
Prior to the use of study drug rescue medication (in the morning upon awakening) the participant evaluated the COPD symptoms of wheezing, cough, and difficulty breathing. A symptom-free night was defined as a combined score of 0 (no symptoms) across all three COPD symptoms evaluated the following morning. Proportion for Baseline included data from the last week before the first dose. Proportion for Endpoint included data across the entire 26-week treatment period.
Time frame: Baseline to Endpoint (26 weeks)
Population: ITT population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI 400/10 mcg BID | Change From Baseline in Proportion of Chronic Obstructive Pulmonary Disease (COPD) Symptom-Free Nights (AM Diary Symptoms) | Baseline | 0.24 Proportion of symptom-free nights | Standard Deviation 0.334 |
| MF/F MDI 400/10 mcg BID | Change From Baseline in Proportion of Chronic Obstructive Pulmonary Disease (COPD) Symptom-Free Nights (AM Diary Symptoms) | Endpoint (Change from Baseline) | 0.13 Proportion of symptom-free nights | Standard Deviation 0.29 |
| MF/F MDI 200/10 mcg BID | Change From Baseline in Proportion of Chronic Obstructive Pulmonary Disease (COPD) Symptom-Free Nights (AM Diary Symptoms) | Baseline | 0.22 Proportion of symptom-free nights | Standard Deviation 0.334 |
| MF/F MDI 200/10 mcg BID | Change From Baseline in Proportion of Chronic Obstructive Pulmonary Disease (COPD) Symptom-Free Nights (AM Diary Symptoms) | Endpoint (Change from Baseline) | 0.17 Proportion of symptom-free nights | Standard Deviation 0.29 |
| MF MDI 400 mcg BID | Change From Baseline in Proportion of Chronic Obstructive Pulmonary Disease (COPD) Symptom-Free Nights (AM Diary Symptoms) | Baseline | 0.24 Proportion of symptom-free nights | Standard Deviation 0.334 |
| MF MDI 400 mcg BID | Change From Baseline in Proportion of Chronic Obstructive Pulmonary Disease (COPD) Symptom-Free Nights (AM Diary Symptoms) | Endpoint (Change from Baseline) | 0.16 Proportion of symptom-free nights | Standard Deviation 0.29 |
| F MDI 10 mcg BID | Change From Baseline in Proportion of Chronic Obstructive Pulmonary Disease (COPD) Symptom-Free Nights (AM Diary Symptoms) | Endpoint (Change from Baseline) | 0.13 Proportion of symptom-free nights | Standard Deviation 0.29 |
| F MDI 10 mcg BID | Change From Baseline in Proportion of Chronic Obstructive Pulmonary Disease (COPD) Symptom-Free Nights (AM Diary Symptoms) | Baseline | 0.25 Proportion of symptom-free nights | Standard Deviation 0.334 |
| Placebo | Change From Baseline in Proportion of Chronic Obstructive Pulmonary Disease (COPD) Symptom-Free Nights (AM Diary Symptoms) | Baseline | 0.24 Proportion of symptom-free nights | Standard Deviation 0.334 |
| Placebo | Change From Baseline in Proportion of Chronic Obstructive Pulmonary Disease (COPD) Symptom-Free Nights (AM Diary Symptoms) | Endpoint (Change from Baseline) | 0.12 Proportion of symptom-free nights | Standard Deviation 0.29 |
Secondary
Change From Baseline to Endpoint in St George's Respiratory Questionaire (SGRQ) Total Score
SGRQ consisted of 76 items aggregated into 3 component scores: symptoms (frequency/severity), activity (cause or limited by breathlessness), impact (social functioning, psychological disturbances from airway disease), & total score. Best health scores have a low numeric value. All component scores & total score ranged from 0-100, with a higher score indicating greater disease burden. A 4-point increase over placebo (and Baseline) was considered the minimum clinically important difference. Endpoint was the last post-baseline non-missing result through the 26 week evaluation carried forward.
Time frame: Baseline to Endpoint (26 weeks)
Population: ITT population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MF/F MDI 400/10 mcg BID | Change From Baseline to Endpoint in St George's Respiratory Questionaire (SGRQ) Total Score | Baseline | 48.22 Score on a scale | Standard Deviation 17.49 |
| MF/F MDI 400/10 mcg BID | Change From Baseline to Endpoint in St George's Respiratory Questionaire (SGRQ) Total Score | Endpoint (Change from Baseline) | -6.04 Score on a scale | Standard Deviation 13.95 |
| MF/F MDI 200/10 mcg BID | Change From Baseline to Endpoint in St George's Respiratory Questionaire (SGRQ) Total Score | Baseline | 47.29 Score on a scale | Standard Deviation 17.49 |
| MF/F MDI 200/10 mcg BID | Change From Baseline to Endpoint in St George's Respiratory Questionaire (SGRQ) Total Score | Endpoint (Change from Baseline) | -7.99 Score on a scale | Standard Deviation 13.95 |
| MF MDI 400 mcg BID | Change From Baseline to Endpoint in St George's Respiratory Questionaire (SGRQ) Total Score | Baseline | 48.27 Score on a scale | Standard Deviation 17.49 |
| MF MDI 400 mcg BID | Change From Baseline to Endpoint in St George's Respiratory Questionaire (SGRQ) Total Score | Endpoint (Change from Baseline) | -5.87 Score on a scale | Standard Deviation 13.95 |
| F MDI 10 mcg BID | Change From Baseline to Endpoint in St George's Respiratory Questionaire (SGRQ) Total Score | Endpoint (Change from Baseline) | -4.93 Score on a scale | Standard Deviation 13.95 |
| F MDI 10 mcg BID | Change From Baseline to Endpoint in St George's Respiratory Questionaire (SGRQ) Total Score | Baseline | 46.27 Score on a scale | Standard Deviation 17.49 |
| Placebo | Change From Baseline to Endpoint in St George's Respiratory Questionaire (SGRQ) Total Score | Baseline | 46.59 Score on a scale | Standard Deviation 17.49 |
| Placebo | Change From Baseline to Endpoint in St George's Respiratory Questionaire (SGRQ) Total Score | Endpoint (Change from Baseline) | -2.88 Score on a scale | Standard Deviation 13.95 |
p-value: 0.02ANCOVA
p-value: <0.001ANCOVA
Secondary
Number of Participants With Mild, Moderate, or Severe COPD Exacerbations
Mild = 12 or more inhalations/day of inhaled rescue medication or 2 or more nebulized treatments/day of inhaled rescue medication. Moderate = treatment with antibiotics or oral steroids. Severe = emergency room treatment or hospitalizations of survival curves. If an event was composed of multiple criteria, the most severe criteria was assigned to the event.
Time frame: Endpoint (26 weeks)
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MF/F MDI 400/10 mcg BID | Number of Participants With Mild, Moderate, or Severe COPD Exacerbations | Mild | 56 Participants |
| MF/F MDI 400/10 mcg BID | Number of Participants With Mild, Moderate, or Severe COPD Exacerbations | Severe | 3 Participants |
| MF/F MDI 400/10 mcg BID | Number of Participants With Mild, Moderate, or Severe COPD Exacerbations | Moderate | 24 Participants |
| MF/F MDI 200/10 mcg BID | Number of Participants With Mild, Moderate, or Severe COPD Exacerbations | Moderate | 20 Participants |
| MF/F MDI 200/10 mcg BID | Number of Participants With Mild, Moderate, or Severe COPD Exacerbations | Mild | 53 Participants |
| MF/F MDI 200/10 mcg BID | Number of Participants With Mild, Moderate, or Severe COPD Exacerbations | Severe | 3 Participants |
| MF MDI 400 mcg BID | Number of Participants With Mild, Moderate, or Severe COPD Exacerbations | Moderate | 29 Participants |
| MF MDI 400 mcg BID | Number of Participants With Mild, Moderate, or Severe COPD Exacerbations | Mild | 49 Participants |
| MF MDI 400 mcg BID | Number of Participants With Mild, Moderate, or Severe COPD Exacerbations | Severe | 5 Participants |
| F MDI 10 mcg BID | Number of Participants With Mild, Moderate, or Severe COPD Exacerbations | Mild | 61 Participants |
| F MDI 10 mcg BID | Number of Participants With Mild, Moderate, or Severe COPD Exacerbations | Severe | 2 Participants |
| F MDI 10 mcg BID | Number of Participants With Mild, Moderate, or Severe COPD Exacerbations | Moderate | 33 Participants |
| Placebo | Number of Participants With Mild, Moderate, or Severe COPD Exacerbations | Moderate | 38 Participants |
| Placebo | Number of Participants With Mild, Moderate, or Severe COPD Exacerbations | Mild | 64 Participants |
| Placebo | Number of Participants With Mild, Moderate, or Severe COPD Exacerbations | Severe | 4 Participants |
Secondary
Number of Participants With Partly Stable COPD
Partly stable COPD was a composite measure that included the following COPD outcomes: (1) No oral steroid rescue medication; (2) No AM or PM COPD weekly average symptom score greater than 2 during at least 7 of 8 weeks; (3) No moderate or severe exacerbations; (4) No unscheduled visits due to COPD worsenings; (5) No study discontinuation due to treatment failure or treatment-related adverse event as determined by the investigator.
Time frame: Endpoint (26 weeks)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MF/F MDI 400/10 mcg BID | Number of Participants With Partly Stable COPD | 91 Participants |
| MF/F MDI 200/10 mcg BID | Number of Participants With Partly Stable COPD | 101 Participants |
| MF MDI 400 mcg BID | Number of Participants With Partly Stable COPD | 92 Participants |
| F MDI 10 mcg BID | Number of Participants With Partly Stable COPD | 98 Participants |
| Placebo | Number of Participants With Partly Stable COPD | 87 Participants |