Efficacy and Safety of Glycopyrronium/Formoterol Fumarate Fixed-dose Combination Relative to Umeclidinium/Vilanterol Fixed-dose Combination Over 24 Weeks in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease

To assess the effects of GFF relative to UV on lung function as measured by change from baseline in morning pre-dose trough FEV1 is defined as the average of the -60 and -30 minute pre-dose values at each visit minus baseline using spirometry. Baseline is defined as the mean of the non-missing -60 and -30 minute values obtained prior to dosing at randomization (Day 1). BR a/s = bronchodilator responsiveness to albuterol/salbutamol.

Time frame: From Baseline (Day 1) up to 24 weeks

Population: The PP analysis set included the subset of the FAS containing participants with post-randomization data obtained prior to important protocol deviations which may have affected efficacy. Only participants with data available for analysis are presented.

To assess the effects of GFF relative to UV on lung function in FAS population as measured by peak change from baseline in FEV1 is defined as the maximum of the FEV1 assessments within the 2 hours post-dosing time windows at each visit minus baseline using spirometry. Baseline is defined as the mean of the non-missing -60 and -30 minute values obtained prior to dosing at randomization (Day 1).

Time frame: From Baseline (Day 1) up to 24 weeks

Population: The FAS included all randomized participants who received at least 1 inhalation of IP from the GFF or UV inhaler (active or placebo).

To assess the effects of GFF relative to UV on lung function in PP analysis set population as measured by peak change from baseline in FEV1 is defined as the maximum of the FEV1 assessments within the 2 hours post-dosing time windows at each visit minus baseline using spirometry. Baseline is defined as the mean of the non-missing -60 and -30 minute values obtained prior to dosing at randomization (Day 1).

Time frame: From Baseline (Day 1) up to 24 weeks

Population: The PP analysis set included the subset of the FAS containing participants with post-randomization data obtained prior to important protocol deviations which may have affected efficacy. Only participants with data available for analysis are presented.

Change from baseline in the 6-item EMSCI Symptom Severity Score was derived by averaging the responses from a participant on the 6 item-level symptom scores (scored on a 4-point scale from 1 to 4, whereas 1= mild and 4= very severe). The EMSCI collected data about the frequency and severity of early morning symptoms and the impact of COPD symptoms on early morning activity in participants with COPD. Participants completed a daily electronic patient-reported outcome (ePRO) questionnaire for their COPD symptoms. Baseline is defined as the average of the non-missing values from the ePRO data collected in the last 7 days before the randomization (Day 1). TI = Time interval.

Time frame: From Baseline (Day -7) up to 24 weeks

Population: The PP analysis set included the subset of the FAS containing participants with post-randomization data obtained prior to important protocol deviations which may have affected efficacy. Only participants with data available for analysis are presented.

Peak change from baseline in IC is defined as the maximum of the IC assessments within the 2 hours post-dosing time windows at each visit minus baseline. Baseline is defined as the average of available evaluable -60 and -30 minute pre-dose assessments conducted at randomization (Day 1).

Time frame: From Baseline (Day 1) up to 24 weeks

Population: The PP analysis set included the subset of the FAS containing participants with post-randomization data obtained prior to important protocol deviations which may have affected efficacy. Only participants with data available for analysis are presented.

The baseline dyspnea index (BDI) and TDI consist of 3 individual components: functional impairment, magnitude of task, and magnitude of effort. For the BDI, each of these 3 components were rated in 5 grades from 0 (very severe) to 4 (no impairment), and were summed to form a baseline total score from 0 to 12. For the TDI, changes in dyspnea were rated for each component by 7 grades from -3 (major deterioration) to +3 (major improvement), and were added to form a TDI focal score from -9 to +9. Baseline is defined as the latest BDI assessment within 7 days before or at randomization (Day 1).

Time frame: From Baseline (Day -7 or 1) up to 24 weeks

Population: The PP analysis set included the subset of the FAS containing participants with post-randomization data obtained prior to important protocol deviations which may have affected efficacy. Only participants with data available for analysis are presented.

The percentage of participants with an increase in FEV1 of \>=100 mL from baseline at 5 minutes post-dosing on Day 1 was determined to assess the early onset of action. Baseline is defined as the average of available evaluable -60 and -30 minute pre-dose assessments conducted at randomization (Day 1). Only data assigned to the 5 minute window was used to determine response. Participants with missing data were considered non-responders for the analysis.

Time frame: 5 minutes post-dose on Day 1

Population: The FAS analysis set included all randomized participants who received at least 1 inhalation of IP from the GFF or UV inhaler (active or placebo).

The CAT is used to quantify the impact of COPD symptoms on health status. The CAT has a scoring range of 0-40, and it is calculated as the sum of the responses given for each of the 8 items (scored on a 6-point scale from 0 to 5), with higher scores indicating a higher impact of COPD symptoms on health status. If the response to 1 of the 8 items is missing, the missing item was considered equal to the average of the 7 non-missing items for that participant. If more than 1 item is missing the score was considered missing. Baseline is defined as the latest assessment within 7 days before or at randomization (Day 1).

Time frame: From Baseline (Day -7 or 1) up to 24 weeks

Population: The PP analysis set included the subset of the FAS containing participants with post-randomization data obtained prior to important protocol deviations which may have affected efficacy. Only participants with data available for analysis are presented.

The number of inhalations of rescue albuterol/salbutamol MDI was recorded in the participant ePRO in the morning and evening. Baseline is defined as the average of the non-missing values from the ePRO data collected in the last 7 days before the randomization (Day 1). a/s = albuterol/salbutamol.

Time frame: From Baseline (Day -7) up to 24 weeks

Population: The rescue medication user analysis set included all participants in the FAS with average baseline rescue albuterol/salbutamol MDI use of \>=1 inhalation/day. Only participants with data available for analysis are presented.

Change from baseline in the 6-item NiSCI Symptom Severity Score was derived by averaging the responses from a participant on the 6 item-level symptom scores (scored on a 4-point scale from 1 to 4, whereas 1= mild and 4= very severe). The NiSCI collected data about the frequency and severity of night-time symptoms and the impact of COPD symptoms on night-time awakenings in participants with COPD. Participants completed a daily ePRO questionnaire for their COPD symptoms. Baseline is defined as the average of the non-missing values from the ePRO data collected in the last 7 days before the randomization (Day 1).

Time frame: From Baseline (Day -7) up to 24 weeks

Population: The PP analysis set included the subset of the FAS containing participants with post-randomization data obtained prior to important protocol deviations which may have affected efficacy. Only participants with data available for analysis are presented.