Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Long-acting beta-agonist, Chronic Obstructive Pulmonary Disease, Umeclidinium, Long-acting muscarinic antagonist, Vilanterol
Brief summary
This is a multicenter, randomized, double-blind, 3-way crossover study to evaluate the lung function response to UMEC 62.5 mcg, VI 25 mcg, and UMEC/VI 62.525 mcg, administered once-daily via a novel dry powder inhaler (NDPI) over 14 days in subjects with COPD. The study consisted of Run in Phase (5 to 7 days), Treatment Phase (made up of 3 treatment periods of 14 days each separated by 10 to 14 days Washout Period) and Follow-up Phase (7 to 9 days after completion of final visit or premature discontinuation). Eligible subjects will be randomized to a sequence of UMEC 62.5 mcg, VI 25 mcg, and UMEC/VI 62.5/25 mcg such that all subjects will receive each treatment. Serial spirometry assessments will be conducted on Day 1 and Day 14 and trough spirometry will be conducted on Day 2 and Day 15 of each treatment period. On Day 1 and 14 of each treatment period vital signs will be assessed and adverse event (AE)s will be recorded throughout the total duration of the study (approximately 12 weeks).
Interventions
DEVICEUmeclidinium 62.5 mcg
Umeclidinium 62.5 mcg once daily in the morning via NDPI.
DEVICEVilanterol 25 mcg
Vilanterol 25 mcg once daily in the morning via NDPI.
Umeclidinium/Vilanterol 62.5/25 mcg once daily in the morning via NDPI.
Sponsors
GlaxoSmithKline
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Type of Patient: Outpatient. * Informed Consent: A signed and dated written informed consent prior to study participation. * Age: Subjects 40 years of age or older at Visit 1. * Gender: Male or female subjects. * A female is eligible to enter and participate in the study if she is of: Non-child bearing potential. Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g. age appropriate, \>45 years, in the absence of hormone replacement therapy. OR Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the acceptable contraceptive methods used consistently and correctly. * Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society. * Smoking History: Current or former cigarette smokers with a history of cigarette smoking of \>= 10 pack-years at Visit 1. * Severity of Disease: A pre- and post-salbutamol FEV1/forced vital capacity (FVC) ratio of \<0.70 and a pre- and post-salbutamol FEV1 of \<=70% of predicted normal values at Visit 1 calculated using Nutrition Health and Examination Survey (NHANES) III reference Equations.
Exclusion criteria
* Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study. * Asthma: A current diagnosis of asthma. * Other Respiratory Disorders: Known alpha-1 antitrypsin deficiency, active lung infections (such as tuberculosis), and lung cancer are absolute exclusionary conditions. A subject, who, in the opinion of the investigator, has any other significant respiratory condition in addition to COPD, should be excluded. Examples may include clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or interstitial lung disease. Allergic rhinitis is not exclusionary. Other Diseases/Abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled and/or a previous history of cancer in remission for \<5 years prior to Visit 1 (localized carcinoma of the skin that has been resected for cure is not exclusionary). * Contraindications: A history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the study physician contraindicates study participation or use of an inhaled anticholinergic. * Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1. * Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Visit 1. * 12-Lead ECG: An abnormal and significant electrocardiogram (ECG) finding from the 12-lead ECG conducted at Visit 1, Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility. The study investigator will determine the medical significance of any ECG abnormalities. * Medication Prior to Spirometry: Unable to withhold salbutamol for the 4 hour period required prior to spirometry testing at each study visit and at each spirometry test performed at home. * Medications Prior to Screening: Use of the following medications according to the following defined time intervals prior to Visit 1: Depot corticosteroids (12 weeks), oral or parenteral corticosteroids (6 weeks), antibiotics (for lower respiratory tract infection) (6 weeks), cytochrome P450 3A4 strong inhibitors2 (6 weeks), long-acting beta agonist (LABA)/ inhaled corticosteroid (ICS) combination products if LABA/ICS therapy is discontinued completely (30 days), use of ICS at a dose \>1000 mcg/day of fluticasone propionate or equivalent (30 days), initiation or discontinuation of ICS use (30 days), tiotropium (7 days), roflumilast (14 days), theophyllines (48 hours), oral leukotriene inhibitors (zafirlukast, montelukast, zileuton) (48 hours), oral beta-agonists long-acting (48 hours), short-acting (12 hours), inhaled long acting beta2-agonists (LABA, e.g., salmeterol, formoterol, indacaterol) (48 hours), LABA/ICS combination products only if discontinuing LABA therapy and switching to ICS monotherapy (48 hours for the LABA component), inhaled sodium cromoglycate or nedocromil sodium (24 hours), inhaled short acting beta2-agonists (4 hours), inhaled short-acting anticholinergic/short-acting beta2-agonist combination products (4 hours) and any other investigational medication 30 days or within 5 drug half-lives (whichever is longer). * Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day. As-needed oxygen use (i.e., \<=12 hours per day) is not exclusionary. * Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (e.g., salbutamol, ipratropium bromide) via nebulized therapy. * Pulmonary Rehabilitation Program: Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded. * Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1. * Affiliation with Investigator Site: Is an investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study. * Inability to read: In the opinion of the Investigator, any subject who is unable to read and/or would not be able to complete a questionnaire.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (BL) in Weighted Mean (WM) 0-6 Hour Forced Expiratory Volume in One Second (FEV1) Obtained Post-dose at Day 14 of Each Treatment Period (TP) by Response Type | Baseline and Day 14 of each treatment period (up to study day 85) | FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. The WM FEV1 was derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The WM FEV1 was calculated using 0-6 hour post-dose measurements at Day 14 of each TP, which included pre-dose (trough value for Day 14 \[mean of the 23 and 24 hour assessments post Day 13 dosing\]) and post-dose 15 minutes (min), 30 min, and 1, 3, and 6 hours. BL is the mean FEV1 values recorded 30 min and 5 min pre-dose on Day 1 of each TP, mean BL is the mean of the BLs for each participant, and period BL is the difference between the BL and the mean BL in each TP for each participant. Change from BL for each TP is the Day 14 value minus the BL value for that TP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants (Par.) Who Were Responsive to UMEC/VI, UMEC or, VI According to FEV1 at Day 1 of Each Treatment Period (TP) | Baseline (BL) and 0-6 hours post-dose (15 minutes, 30 minutes, and 1, 3, and 6 hours post-dose) on Day 1 of each treatment period (up to study day 66) | A responder is a par. with an increase from BL of \>=12% and 200 milliliters (mL) at \>=1 time point over 0-6 hours post-dose (PD) in FEV1 on Day 1. A non-responder (NR) is a par. with \>=1 FEV1 assessment over 0-6 hours PD on Day 1 but no increase from BL of \>=12% and 200 mL at any assessment(s). Missing: no FEV1 data recorded over 0-6 hours PD on Day 1. Response type is defined based on a par.'s response to each individual monotherapy treatment. A responder to UMEC is a par. who is a responder in the UMEC treatment period (TP) and either a NR or has missing data in the VI TP. A responder to VI is a par. who is a responder in the VI TP and either a NR or has missing data in the UMEC TP. A responder to UMEC and VI is a par. who is a responder in both the UMEC and VI TPs. A responder to neither is a par. who is a NR in both the UMEC and VI TPs. Missing: a par. who has missing data in both the UMEC and VI TPs, or who has missing data in one monotherapy period and is a NR in the other. |
| Number of Participants With a Larger Change From Baseline in 0-6 Hour Weighted Mean FEV1 at Day 14 of Each Treatment Period With UMEC/VI Compared With UMEC and VI Alone | Baseline and Day 14 of each treatment period (up to study day 85) | The number of participants with a larger change from Baseline in weighted mean FEV1 with UMEC/VI compared with UMEC and VI alone was recorded. Participants who improved on UMEC/VI had a larger change from Baseline difference in 0-6 hour weighted mean FEV1 on Day 14 on UMEC/VI compared to UMEC or VI alone. Baseline is the mean FEV1 values recorded 30 min and 5 min pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline for each treatment period is the Day 14 value minus the Baseline value for that treatment period. |
| Change From Baseline in Clinic Visit Pre-dose Trough FEV1 at Day 15 of Each Treatment Period | Baseline and Day 15 of each treatment period (up to study day 81) | Trough FEV1 on Treatment Day 15 is defined as the mean of the FEV1 values obtained at 23 and 24 hours after dosing on Day 14. Analysis was performed using an ANCOVA model with covariates of treatment, period, mean Baseline (BL), period BL, response type, and treatment by response type interaction. A participant is a reponder to UMEC if they were a responder to UMEC monotherapy or a responder to both UMEC monotherapy and VI monotherapy. A participant is a responder to VI if they were a responder to VI monotherapy or a responder to both UMEC monotherapy or VI monotherapy. BL is the mean FEV1 recorded 30 min and 5 min pre-dose on Day 1 of each treatment period, mean BL is the mean of the BLs for each participant, and period BL is the difference between BL and the mean BL in each treatment period for each participant. Change from BL for each treatment period is the Day 15 value minus the BL value for that treatment period. |
Countries
Slovakia, Ukraine
Participant flow
Pre-assignment details
Participants who met the eligibility criteria at Screening (Visit 1) completed a 5- to 7-day Run-in Period prior to being randomized to 1 of 6 treatment sequences. The treatment phase was comprised of three 14-day treatment periods, each separated by a 10- to 14-day washout period.
Participants by arm
| Arm | Count |
|---|---|
| UMEC 62.5 µg, VI 25 µg, UMEC/VI 62.5/25 µg All participants received one of the following three treatments in one of three treatment periods QD from the DPI for 14 days: UMEC 62.5 µg inhalation powder; VI 25 µg inhalation powder; and UMEC/VI 62.5/25 µg inhalation powder. Participants were randomized to receive treatment in one of the six following sequences: (1) UMEC 62.5 µg, VI 25 µg, UMEC/VI 62.5/25 µg; (2) VI 25 µg, UMEC/VI 62.5/25 µg, UMEC 62.5 µg; (3) UMEC/VI 62.5/25 µg, UMEC 62.5 µg, VI 25 µg; (4) UMEC 62.5 µg, UMEC/VI 62.5/25 µg, VI 25 µg; (5) VI 25 µg, UMEC 62.5 µg, UMEC/VI 62.5/25 µg; (6) UMEC/VI 62.5/25 µg, VI 25 µg, UMEC 62.5 µg. The three treatment periods were separated by a washout period of 10 to 14 days. | 207 |
| Total | 207 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Treatment Period 1 (14 Days) | Lack of Efficacy | 0 | 0 | 1 | 0 | 0 | 0 |
| Treatment Period 1 (14 Days) | Withdrawal by Subject | 0 | 1 | 0 | 2 | 1 | 0 |
| Treatment Period 2 (14 Days) | Protocol Violation | 1 | 1 | 2 | 1 | 0 | 0 |
| Treatment Period 3 (14 Days) | Adverse Event | 0 | 0 | 1 | 0 | 0 | 1 |
| Treatment Period 3 (14 Days) | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 1 |
| Treatment Period 3 (14 Days) | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
| Washout Period 1 (10 to 14 Days) | Lack of Efficacy | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | UMEC 62.5 µg, VI 25 µg, UMEC/VI 62.5/25 µg |
|---|---|
| Age, Continuous | 60.5 Years STANDARD_DEVIATION 7.99 |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 207 participants |
| Sex: Female, Male Female | 38 Participants |
| Sex: Female, Male Male | 169 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 202 | 10 / 200 | 10 / 202 |
| serious Total, serious adverse events | 1 / 202 | 1 / 200 | 1 / 202 |
Outcome results
Primary
Change From Baseline (BL) in Weighted Mean (WM) 0-6 Hour Forced Expiratory Volume in One Second (FEV1) Obtained Post-dose at Day 14 of Each Treatment Period (TP) by Response Type
FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. The WM FEV1 was derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The WM FEV1 was calculated using 0-6 hour post-dose measurements at Day 14 of each TP, which included pre-dose (trough value for Day 14 \[mean of the 23 and 24 hour assessments post Day 13 dosing\]) and post-dose 15 minutes (min), 30 min, and 1, 3, and 6 hours. BL is the mean FEV1 values recorded 30 min and 5 min pre-dose on Day 1 of each TP, mean BL is the mean of the BLs for each participant, and period BL is the difference between the BL and the mean BL in each TP for each participant. Change from BL for each TP is the Day 14 value minus the BL value for that TP.
Time frame: Baseline and Day 14 of each treatment period (up to study day 85)
Population: Intent-to-Treat (ITT) Population: all participants (par.) randomized to treatment who received \>=1 dose of randomized study medication in a TP. Only par. available at the specified time points were analyzed. Different par. may have been analyzed for different parameters; the overall number of par, analyzed reflects everyone in the ITT Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| UMEC 62.5 µg | Change From Baseline (BL) in Weighted Mean (WM) 0-6 Hour Forced Expiratory Volume in One Second (FEV1) Obtained Post-dose at Day 14 of Each Treatment Period (TP) by Response Type | Responder to VI, n=78, 77, 80 | 0.135 Liters | Standard Error 0.0182 |
| UMEC 62.5 µg | Change From Baseline (BL) in Weighted Mean (WM) 0-6 Hour Forced Expiratory Volume in One Second (FEV1) Obtained Post-dose at Day 14 of Each Treatment Period (TP) by Response Type | Responder to UMEC, n=79, 78, 81 | 0.155 Liters | Standard Error 0.0184 |
| UMEC 62.5 µg | Change From Baseline (BL) in Weighted Mean (WM) 0-6 Hour Forced Expiratory Volume in One Second (FEV1) Obtained Post-dose at Day 14 of Each Treatment Period (TP) by Response Type | Responder to Neither, n=80, 79, 80 | 0.014 Liters | Standard Error 0.0179 |
| VI 25 µg | Change From Baseline (BL) in Weighted Mean (WM) 0-6 Hour Forced Expiratory Volume in One Second (FEV1) Obtained Post-dose at Day 14 of Each Treatment Period (TP) by Response Type | Responder to VI, n=78, 77, 80 | 0.182 Liters | Standard Error 0.0183 |
| VI 25 µg | Change From Baseline (BL) in Weighted Mean (WM) 0-6 Hour Forced Expiratory Volume in One Second (FEV1) Obtained Post-dose at Day 14 of Each Treatment Period (TP) by Response Type | Responder to UMEC, n=79, 78, 81 | 0.156 Liters | Standard Error 0.0185 |
| VI 25 µg | Change From Baseline (BL) in Weighted Mean (WM) 0-6 Hour Forced Expiratory Volume in One Second (FEV1) Obtained Post-dose at Day 14 of Each Treatment Period (TP) by Response Type | Responder to Neither, n=80, 79, 80 | 0.035 Liters | Standard Error 0.018 |
| UMEC/VI 62.5/25 µg | Change From Baseline (BL) in Weighted Mean (WM) 0-6 Hour Forced Expiratory Volume in One Second (FEV1) Obtained Post-dose at Day 14 of Each Treatment Period (TP) by Response Type | Responder to UMEC, n=79, 78, 81 | 0.263 Liters | Standard Error 0.0179 |
| UMEC/VI 62.5/25 µg | Change From Baseline (BL) in Weighted Mean (WM) 0-6 Hour Forced Expiratory Volume in One Second (FEV1) Obtained Post-dose at Day 14 of Each Treatment Period (TP) by Response Type | Responder to Neither, n=80, 79, 80 | 0.092 Liters | Standard Error 0.0179 |
| UMEC/VI 62.5/25 µg | Change From Baseline (BL) in Weighted Mean (WM) 0-6 Hour Forced Expiratory Volume in One Second (FEV1) Obtained Post-dose at Day 14 of Each Treatment Period (TP) by Response Type | Responder to VI, n=78, 77, 80 | 0.264 Liters | Standard Error 0.018 |
p-value: <0.00195% CI: [0.065, 0.151]ANCOVA
p-value: <0.00195% CI: [0.064, 0.149]ANCOVA
p-value: <0.00195% CI: [0.086, 0.171]ANCOVA
p-value: <0.00195% CI: [0.04, 0.125]ANCOVA
p-value: <0.00195% CI: [0.036, 0.12]ANCOVA
p-value: 0.00895% CI: [0.015, 0.099]ANCOVA
Secondary
Change From Baseline in Clinic Visit Pre-dose Trough FEV1 at Day 15 of Each Treatment Period
Trough FEV1 on Treatment Day 15 is defined as the mean of the FEV1 values obtained at 23 and 24 hours after dosing on Day 14. Analysis was performed using an ANCOVA model with covariates of treatment, period, mean Baseline (BL), period BL, response type, and treatment by response type interaction. A participant is a reponder to UMEC if they were a responder to UMEC monotherapy or a responder to both UMEC monotherapy and VI monotherapy. A participant is a responder to VI if they were a responder to VI monotherapy or a responder to both UMEC monotherapy or VI monotherapy. BL is the mean FEV1 recorded 30 min and 5 min pre-dose on Day 1 of each treatment period, mean BL is the mean of the BLs for each participant, and period BL is the difference between BL and the mean BL in each treatment period for each participant. Change from BL for each treatment period is the Day 15 value minus the BL value for that treatment period.
Time frame: Baseline and Day 15 of each treatment period (up to study day 81)
Population: ITT Population. Only those participants available at the specified time points were analyzed. Different participants may have been analyzed for different parameters; the overall number of participants analyzed reflects everyone in the ITT Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| UMEC 62.5 µg | Change From Baseline in Clinic Visit Pre-dose Trough FEV1 at Day 15 of Each Treatment Period | Responder to Neither, n=80, 79, 79 | 0.016 Liters | Standard Error 0.019 |
| UMEC 62.5 µg | Change From Baseline in Clinic Visit Pre-dose Trough FEV1 at Day 15 of Each Treatment Period | Responder to VI, n=78, 78, 80 | 0.088 Liters | Standard Error 0.0194 |
| UMEC 62.5 µg | Change From Baseline in Clinic Visit Pre-dose Trough FEV1 at Day 15 of Each Treatment Period | Responder to UMEC, n=79, 78, 80 | 0.105 Liters | Standard Error 0.0196 |
| VI 25 µg | Change From Baseline in Clinic Visit Pre-dose Trough FEV1 at Day 15 of Each Treatment Period | Responder to Neither, n=80, 79, 79 | 0.004 Liters | Standard Error 0.0191 |
| VI 25 µg | Change From Baseline in Clinic Visit Pre-dose Trough FEV1 at Day 15 of Each Treatment Period | Responder to UMEC, n=79, 78, 80 | 0.086 Liters | Standard Error 0.0197 |
| VI 25 µg | Change From Baseline in Clinic Visit Pre-dose Trough FEV1 at Day 15 of Each Treatment Period | Responder to VI, n=78, 78, 80 | 0.106 Liters | Standard Error 0.0193 |
| UMEC/VI 62.5/25 µg | Change From Baseline in Clinic Visit Pre-dose Trough FEV1 at Day 15 of Each Treatment Period | Responder to Neither, n=80, 79, 79 | 0.062 Liters | Standard Error 0.0191 |
| UMEC/VI 62.5/25 µg | Change From Baseline in Clinic Visit Pre-dose Trough FEV1 at Day 15 of Each Treatment Period | Responder to VI, n=78, 78, 80 | 0.166 Liters | Standard Error 0.0191 |
| UMEC/VI 62.5/25 µg | Change From Baseline in Clinic Visit Pre-dose Trough FEV1 at Day 15 of Each Treatment Period | Responder to UMEC, n=79, 78, 80 | 0.170 Liters | Standard Error 0.0191 |
Secondary
Number of Participants (Par.) Who Were Responsive to UMEC/VI, UMEC or, VI According to FEV1 at Day 1 of Each Treatment Period (TP)
A responder is a par. with an increase from BL of \>=12% and 200 milliliters (mL) at \>=1 time point over 0-6 hours post-dose (PD) in FEV1 on Day 1. A non-responder (NR) is a par. with \>=1 FEV1 assessment over 0-6 hours PD on Day 1 but no increase from BL of \>=12% and 200 mL at any assessment(s). Missing: no FEV1 data recorded over 0-6 hours PD on Day 1. Response type is defined based on a par.'s response to each individual monotherapy treatment. A responder to UMEC is a par. who is a responder in the UMEC treatment period (TP) and either a NR or has missing data in the VI TP. A responder to VI is a par. who is a responder in the VI TP and either a NR or has missing data in the UMEC TP. A responder to UMEC and VI is a par. who is a responder in both the UMEC and VI TPs. A responder to neither is a par. who is a NR in both the UMEC and VI TPs. Missing: a par. who has missing data in both the UMEC and VI TPs, or who has missing data in one monotherapy period and is a NR in the other.
Time frame: Baseline (BL) and 0-6 hours post-dose (15 minutes, 30 minutes, and 1, 3, and 6 hours post-dose) on Day 1 of each treatment period (up to study day 66)
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| UMEC 62.5 µg | Number of Participants (Par.) Who Were Responsive to UMEC/VI, UMEC or, VI According to FEV1 at Day 1 of Each Treatment Period (TP) | Responder | 81 participants |
| UMEC 62.5 µg | Number of Participants (Par.) Who Were Responsive to UMEC/VI, UMEC or, VI According to FEV1 at Day 1 of Each Treatment Period (TP) | Non-responder | 121 participants |
| VI 25 µg | Number of Participants (Par.) Who Were Responsive to UMEC/VI, UMEC or, VI According to FEV1 at Day 1 of Each Treatment Period (TP) | Responder | 81 participants |
| VI 25 µg | Number of Participants (Par.) Who Were Responsive to UMEC/VI, UMEC or, VI According to FEV1 at Day 1 of Each Treatment Period (TP) | Non-responder | 119 participants |
| UMEC/VI 62.5/25 µg | Number of Participants (Par.) Who Were Responsive to UMEC/VI, UMEC or, VI According to FEV1 at Day 1 of Each Treatment Period (TP) | Responder | 103 participants |
| UMEC/VI 62.5/25 µg | Number of Participants (Par.) Who Were Responsive to UMEC/VI, UMEC or, VI According to FEV1 at Day 1 of Each Treatment Period (TP) | Non-responder | 99 participants |
Secondary
Number of Participants With a Larger Change From Baseline in 0-6 Hour Weighted Mean FEV1 at Day 14 of Each Treatment Period With UMEC/VI Compared With UMEC and VI Alone
The number of participants with a larger change from Baseline in weighted mean FEV1 with UMEC/VI compared with UMEC and VI alone was recorded. Participants who improved on UMEC/VI had a larger change from Baseline difference in 0-6 hour weighted mean FEV1 on Day 14 on UMEC/VI compared to UMEC or VI alone. Baseline is the mean FEV1 values recorded 30 min and 5 min pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline for each treatment period is the Day 14 value minus the Baseline value for that treatment period.
Time frame: Baseline and Day 14 of each treatment period (up to study day 85)
Population: ITT Population. Only those participants available at the indicated time point were assessed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| UMEC 62.5 µg | Number of Participants With a Larger Change From Baseline in 0-6 Hour Weighted Mean FEV1 at Day 14 of Each Treatment Period With UMEC/VI Compared With UMEC and VI Alone | Improved on UMEC/VI | 124 participants |
| UMEC 62.5 µg | Number of Participants With a Larger Change From Baseline in 0-6 Hour Weighted Mean FEV1 at Day 14 of Each Treatment Period With UMEC/VI Compared With UMEC and VI Alone | Not improved on UMEC/VI | 69 participants |
| VI 25 µg | Number of Participants With a Larger Change From Baseline in 0-6 Hour Weighted Mean FEV1 at Day 14 of Each Treatment Period With UMEC/VI Compared With UMEC and VI Alone | Improved on UMEC/VI | 130 participants |
| VI 25 µg | Number of Participants With a Larger Change From Baseline in 0-6 Hour Weighted Mean FEV1 at Day 14 of Each Treatment Period With UMEC/VI Compared With UMEC and VI Alone | Not improved on UMEC/VI | 62 participants |