Trial Outcomes & Findings for A 24 Week Efficacy Study of Inhaled Umeclidinium (UMEC) in Patients of Chronic Obstructive Pulmonary Disease (COPD) Using a Novel Dry Powder Inhaler (NDPI) (NCT NCT02184611)

Last Updated: 2020-06-29

Results Overview

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on Treatment Day 169 was defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Treatment Day 168 (i.e. at Week 24). Baseline FEV1 is defined as the mean of the two assessments made pre-dose at Visit 2 (Day 1). Change from Baseline was calculated by subtracting the value on-treatment from the Baseline value. Modified intent-to-treat (mITT) Population comprised of all participants randomized to treatment who received at least one dose of the study medication in the treatment period.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

308 participants

Primary outcome timeframe

Baseline (Day 1) and Day 169

Results posted on

2020-06-29

Participant Flow

The study was conducted from 09 May 2016 to 08 November 2017 at 26 centers (21 centers in China and 5 centers in the Republic of Korea). A total of 306 participants were included in the Modified Intent-To-Treat (MITT) Population which comprised of all participants randomized to treatment who received at least one dose of study medication.

Total participants screened were 440; of which, pre-screen failures: 28, Screen failures: 94 (inclusion/exclusion criteria not met: 82, withdrew consent \[WC\]: 9, adverse event: 2, lost to follow up: 1) and Run in failures: 10 (continuation criteria not met: 6, WC: 4). The remaining 308 participants were randomized (but 2 were randomized in error).

Participant milestones

Participant milestones
Measure	Placebo Participants received matching placebo to umeclidinium (UMEC) via ELLIPTA® novel dry powder inhaler (DPI) once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg Participants received UMEC 62.5 micrograms (mcg) via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Overall Study STARTED	101	205
Overall Study COMPLETED	80	177
Overall Study NOT COMPLETED	21	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received matching placebo to umeclidinium (UMEC) via ELLIPTA® novel dry powder inhaler (DPI) once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg Participants received UMEC 62.5 micrograms (mcg) via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Overall Study Lack of Efficacy	11	15
Overall Study Withdrawal by Subject	5	6
Overall Study Adverse Event	4	5
Overall Study Protocol Violation	1	1
Overall Study Protocol defined stopping criteria	0	1

Baseline Characteristics

A 24 Week Efficacy Study of Inhaled Umeclidinium (UMEC) in Patients of Chronic Obstructive Pulmonary Disease (COPD) Using a Novel Dry Powder Inhaler (NDPI)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=101 Participants Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=205 Participants Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.	Total n=306 Participants Total of all reporting groups
Age, Continuous	65.7 Years STANDARD_DEVIATION 7.05 • n=5 Participants	65.5 Years STANDARD_DEVIATION 6.89 • n=7 Participants	65.6 Years STANDARD_DEVIATION 6.93 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	12 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	97 Participants n=5 Participants	193 Participants n=7 Participants	290 Participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	101 Participants n=5 Participants	205 Participants n=7 Participants	306 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 169

Population: mITT Population. Only those participants with data available at the indicated time point were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=80 Participants Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=176 Participants Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Change From Baseline in Trough (Pre-bronchodilator) Forced Expiratory Volume in 1 Second (FEV1) on Treatment Day 169	-0.022 Liters Standard Error 0.0171	0.131 Liters Standard Error 0.0117

SECONDARY outcome

Timeframe: Week 24 (Day 168)

Population: mITT Population. Only those participants with data available at the indicated time point were analyzed.

The Baseline Dyspnea Index (BDI) is used to measure the severity of dyspnea in participants at Baseline . The TDI measures changes in dyspnea severity from Baseline, as established by the BDI. TDI is formed of 3 individual scales that assess change in functional impairment, change in magnitude of task and change in magnitude of effort. The instrument is scored on a 7-point scale from -3 (major deterioration) to +3 (major improvement) for each category. Total scores (3 categories) range from -9 to +9 with lower scores indicating more deterioration in the severity of dyspnoea. A change of \>=1 units is considered to be the minimum clinically important difference (MCID) for the TDI.

Outcome measures

Outcome measures
Measure	Placebo n=80 Participants Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=176 Participants Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Transition Dyspnea Index (TDI) Focal Score at Week 24 (Day 168)	1.6 Scores on a scale Standard Error 0.26	2.5 Scores on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: Baseline (pre-dose on Day 1) and Day 1 (0 to 6 hours)

Population: mITT Population. Only those participants with data available at the indicated time point were analyzed.

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Weighted mean FEV1 was calculated over the nominal 0 to 6 hour post dose period. Values from post-dose assessments which were actually before the time of dosing were excluded from the calculation. The 0 hour value is the average value obtained 30 minutes and 5 minutes pre-dose, and both the 0 hour and 6 hour values must be present for a 0- to 6 hour weighted mean to be calculated. The 0 -to 6 hour weighted mean was derived by calculating the area under the FEV1 curve over the nominal time points of 0 hour, 15 and 30 minutes, 1, 3 and 6 hours, using the trapezoidal rule, and then dividing by the actual time between dosing and the 6 hour assessment. Baseline value for FEV1 was calculated from the values measured 30 minutes and 5 minutes pre-dose on Day 1. Change from Baseline was calculated by subtracting the value on-treatment from the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=101 Participants Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=203 Participants Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Change From Baseline in Weighted Mean FEV1 Over 0 to 6 Hours Post-dose on Day 1	0.011 Liters Standard Error 0.0091	0.136 Liters Standard Error 0.0064

SECONDARY outcome

Timeframe: Up to Day 178

Population: mITT Population

AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or is associated with liver injury and impaired liver function.

Outcome measures

Outcome measures
Measure	Placebo n=101 Participants Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=205 Participants Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Number of Participants With Adverse Events (AE) and Serious AE (SAE) AE	56 Participants	122 Participants
Number of Participants With Adverse Events (AE) and Serious AE (SAE) SAE	9 Participants	17 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 169 (Visit 9)

Population: mITT Population

Vital signs (SBP and DBP) were obtained after participants had rested for approximately 5 minutes and before performing electrocardiogram (ECG) and spirometry testing. A single set of values was obtained. Baseline was the most recent recorded value before dosing on Day 1 at schedule visit. Change from Baseline was calculated by subtracting the value on-treatment from the Baseline value. Anytime post-Baseline values have been presented for SBP and DBP respectively.

Outcome measures

Outcome measures
Measure	Placebo n=101 Participants Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=205 Participants Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Anytime post-Baseline	11.1 Millimeters of mercury Standard Deviation 11.25	11.4 Millimeters of mercury Standard Deviation 10.64
Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Anytime post-Baseline	-10.2 Millimeters of mercury Standard Deviation 7.55	-10.8 Millimeters of mercury Standard Deviation 8.03

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 169 (Visit 9)

Population: mITT Population

Vital sign pulse rate was obtained after participants had rested for approximately 5 minutes and before performing electrocardiogram (ECG) and spirometry testing. A single set of values was obtained. Baseline was the most recent recorded value before dosing on Day 1 at schedule visit. Change from Baseline was calculated by subtracting the value on-treatment from the Baseline value. Anytime post-Baseline values have been presented for pulse rate.

Outcome measures

Outcome measures
Measure	Placebo n=101 Participants Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=205 Participants Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Change From Baseline in Vital Sign Parameter: Pulse Rate	10.7 Beats/minute Standard Deviation 10.94	8.2 Beats/minute Standard Deviation 9.47

SECONDARY outcome

Timeframe: Up to Day 169 (Visit 9)

Population: mITT Population

A 12-lead ECG measurement was obtained after measurement of vital signs and before spirometry testing. Participants should be placed in the supine position for the ECG measurements. Any ECG abnormality recorded by a participant after the start of study treatment was included in the any-time post-Baseline record of all ECG abnormalities. Partcipants with abnormal ECG interpretation have been presented.

Outcome measures

Outcome measures
Measure	Placebo n=101 Participants Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=205 Participants Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Number of Participants With Electrocardiogram (ECG) Abnormalities Any Time Post Baseline	51 Participants	105 Participants

SECONDARY outcome

Timeframe: Up to Day 168 (Visit 8)

Population: mITT Population. Only those participants available at the specified time point were analyzed represented by n=x, x in the category titles.

Hematology parameters included basophils (normal range 0 to 0.2 giga cells/Liter), eosinophils (0.05 to 0.55 giga cells/Liter), hematocrit (0.36 to 0.49 percentage of red blood cells in blood), hemoglobin (118 to 168 gram/Liter), lymphocytes (0.85 to 4.1 giga cells/Liter), monocytes (0.2 to 1.1 giga cells/Liter), platelet count (PC)(130 to 400 giga cells/Liter), neutrophils (1.8 to 8 giga cells/Liter), total neutrophils (TN) (1.8 to 8 giga cells/Liter), white blood cell \[WBC\] count (3.8 to 10.8 giga cells/Liter). Only categories with non-zero (high and low) values at any time post Baseline have been presented.

Outcome measures

Outcome measures
Measure	Placebo n=96 Participants Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=196 Participants Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline WBC count, Any time post Baseline, Low,n=96,196	0 Participants	1 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline Eosinophils, Any time post Baseline, High,n=96,196	8 Participants	11 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline Eosinophils, Any time post Baseline, Low,n=96,196	19 Participants	37 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline Hematocrit, Any time post Baseline, High,n=96,196	14 Participants	35 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline Hematocrit, Any time post Baseline, Low,n=96,196	3 Participants	21 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline Hemoglobin, Any time post Baseline, High,n=96,196	2 Participants	5 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline Hemoglobin, Any time post Baseline, Low,n=96,196	7 Participants	28 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline Lymphocytes, Any time post Baseline, High,n=96,196	1 Participants	3 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline Lymphocytes, Any time post Baseline, Low,n=96,196	3 Participants	10 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline Monocytes, Any time post Baseline, High,n=96,196	0 Participants	1 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline Monocytes, Any time post Baseline, Low,n=96,196	14 Participants	28 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline PC, Any time post Baseline, High, n=96,195	1 Participants	0 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline PC, Any time post Baseline, Low, n=96,195	7 Participants	15 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline Neutrophils, Any time post Baseline, High,n=96,196	8 Participants	12 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline Neutrophils,Any time post Baseline, Low,n=96,196	0 Participants	2 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline TN, Any time post Baseline, High, n=96,196	8 Participants	12 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline TN, Any time post Baseline, Low, n=96,196	0 Participants	2 Participants
Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline WBC count, Any time post Baseline, High,n=96,196	7 Participants	12 Participants

SECONDARY outcome

Timeframe: Up to Day 168 (Visit 8)

Population: mITT Population. Only those participants with data available at the indicated time point were analyzed.

Clinical chemistry parameters assessed included albumin (normal range 32 to 50 grams/Liter \[G/L\]), alkaline phosphatase (20 to 125 international units/Liter \[IU/L\]), alanine aminotransferase \[ALT\] (0 to 48 IU/L), aspartate aminotransferase \[AST\] (0 to 55 IU/L), direct bilirubin (0 to 6 micromoles/liter \[umol/l\]), indirect bilirubin (0 to 22 umol/l), total bilirubin (0 to 22 umol/l), calcium (2.12 to 2.56 milimoles/liter \[mmol/l\]), chloride (95 to 108 mmol/l), carbon dioxide \[CO2\] content/bicarbonate (20 to 32 mmol/l), creatinine (67.2 to 129.1 umol/l), creatinine phosphokinase \[CPK\] (0 to 235 IU/L), gamma glutamyl transferase \[GGT\] (0 to75 IU/L), glucose (3.9 to 6.9 mmol/l), phosphorus (0.7 to 1.4 mmol/l), potassium (3.5 to 5.3 mmol/l), protein total (58 to 81 G/L), sodium (135 to 146 mmol/l), urea nitrogen (2.5 to 10.5 mmol/l), uric acid (240 to 510 umol/l). Only categories with non-zero (high and low) values at any time post Baseline have been presented.

Outcome measures

Outcome measures
Measure	Placebo n=96 Participants Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=196 Participants Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline ALT, Any time post Baseline, High	5 Participants	5 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Albumin, Any time post Baseline, High	0 Participants	1 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Albumin, Any time post Baseline, Low	0 Participants	1 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Alkaline Phosphatase, Any time post Baseline, High	3 Participants	5 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Alkaline Phosphatase, Any time post Baseline, Low	0 Participants	1 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline AST, Any time post Baseline, High	0 Participants	3 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Calcium, Any time post Baseline, Low	2 Participants	1 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline CO2 content,Any time post Baseline, Low	6 Participants	26 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Chloride, Any time post Baseline, High	0 Participants	8 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Chloride, Any time post Baseline, Low	2 Participants	2 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Creatine Kinase, Any time post Baseline, High	4 Participants	4 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Creatinine, Any time post Baseline, High	0 Participants	1 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Creatinine, Any time post Baseline, Low	20 Participants	51 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Direct Bilirubin, Any time post Baseline, High	1 Participants	4 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline GGT, Any time post Baseline, High	10 Participants	12 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Glucose, Any time post Baseline, High	23 Participants	46 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Glucose, Any time post Baseline, Low	2 Participants	1 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Indirect Bilirubin, Any time post Baseline, High	2 Participants	5 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Phosphorus, Any time post Baseline, High	9 Participants	8 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Phosphorus, Any time post Baseline, Low	3 Participants	5 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Potassium, Any time post Baseline, High	1 Participants	1 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Potassium, Any time post Baseline, Low	4 Participants	4 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Sodium, Any time post Baseline, High	1 Participants	1 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Sodium, Any time post Baseline, Low	1 Participants	4 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Total Bilirubin, Any time post Baseline, High	4 Participants	8 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Total Protein, Any time post Baseline, High	1 Participants	2 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Total Protein, Any time post Baseline, Low	0 Participants	1 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Urea nitrogen, Any time post Baseline, High	5 Participants	5 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Urea nitrogen, Any time post Baseline, Low	2 Participants	1 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Uric acid, Any time post Baseline, High	6 Participants	13 Participants
Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Uric acid, Any time post Baseline, Low	13 Participants	10 Participants

SECONDARY outcome

Timeframe: Up to Day 168 (Visit 8)

Population: mITT Population

Urinalysis parameters assessed were urine ketones, urine bilirubin, urine glucose, urine leukocyte esterase test for detecting WBC and urine protein. In this dipstick test, the level of bilirubin, glucose, leukocyte esterase and protein in urine samples was recorded as negative, trace, 1+, 2+, and 3+ (the plus sign increases with a higher level of bilirubin, glucose, leukocyte esterase, or proteins in the urine: 1+=slightly positive, 2+=positive, 3+=high positive). Urine samples were collected for the measurement of urinalysis parameters by dipstick method up to Day 168 (Visit 8). Only categories with significant values have been presented. Only those participants with data available at the indicated time point were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=80 Participants Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=178 Participants Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Number of Participants With Abnormal Urinalysis Parameters by Dipstick Method Urine protein, Day 168, Trace	10 Participants	6 Participants
Number of Participants With Abnormal Urinalysis Parameters by Dipstick Method Urine Bilirubin, Day 168, 1+	2 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Parameters by Dipstick Method Urine Bilirubin, Day 168, 2+	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameters by Dipstick Method Urine Glucose, Day 168, 1+	3 Participants	6 Participants
Number of Participants With Abnormal Urinalysis Parameters by Dipstick Method Urine Glucose, Day 168, 2+	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Parameters by Dipstick Method Urine Glucose, Day 168, 3+	2 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Parameters by Dipstick Method Urine Glucose, Day 168, Trace	2 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Parameters by Dipstick Method Urine leukocyte esterase, Day 168, 1+	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Parameters by Dipstick Method Urine leukocyte esterase, Day 168, 2+	0 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Parameters by Dipstick Method Urine leukocyte esterase, Day 168, Trace	4 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Parameters by Dipstick Method Urine protein, Day 168, 1+	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Parameters by Dipstick Method Urine protein, Day 168, 2+	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 168 (Visit 8)

Population: mITT Population

Urinary pH measurement is a routine part of urinalysis. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 to 6.0). Urine samples were collected for the measurement of urine pH up to Day 168 (Visit 8). Only categories with significant values have been presented. Only those participants with data available at the indicated time point were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=80 Participants Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=178 Participants Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Mean Urine Potential of Hydrogen (pH)	6.16 pH Standard Deviation 0.520	6.25 pH Standard Deviation 0.632

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 28, Day 84 and Day 168

Population: mITT Population. Only those participants available at the specified time points were analyzed (represented by n=x,x in the category titles).

The SGRQ is designed to measure health-related quality of life (HRQoL) in participants with diseases of airway obstruction with the use of 76 items grouped into three domains: symptoms, activity and impact. The questions are designed to be self-completed by the participant based on recall of the past 4 weeks. Domain score =sum of the weighted scores for the non-missing items within each domain/maximum possible score for those non-missing items x 100. The SGRQ total score= sum of the weighted scores from all 76 items /maximum possible score for the SGRQ x100. Scores range from 0, representing the best possible health status, to 100, representing the worst possible health status. A decrease in score indicates an improvement in HRQoL whereas increase indicates deterioration in HRQoL. Baseline was the most recent recorded value before dosing on Day 1 at schedule visit. Change from Baseline was calculated by subtracting the value on-treatment from the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=101 Participants Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=205 Participants Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Days 28, 84 and 168 Day 28, n=91,188	-1.45 Scores on a scale Standard Error 1.174	-5.84 Scores on a scale Standard Error 0.813
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Days 28, 84 and 168 Day 84, n= 84,183	-2.46 Scores on a scale Standard Error 1.268	-7.05 Scores on a scale Standard Error 0.860
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Days 28, 84 and 168 Day 168, n=78,176	-4.31 Scores on a scale Standard Error 1.316	-7.34 Scores on a scale Standard Error 0.882

SECONDARY outcome

Timeframe: Baseline (Day 1) and Days 28, 84 and 168

Population: mITT Population. Only those participants available at the specified time points were analyzed (represented by n=x, x in the category titles).

The CAT is an 8-item, participant-completed instrument that covers symptoms such as cough, phlegm, chest tightness and breathlessness, and disease impacts including physical activity, confidence, sleep and energy. The CAT asks participant to score each item according to their current experience; there is no specific recall period. Items are scored on a 6-point response scale, with a score of 0 representing the participants are not experiencing the symptom/impact at all and a score of 5 representing a maximal symptom or impact. All items have equal weighting and so the total score is simply the sum of all scores and can range from 0 to a maximum of 40, with higher scores indicating a worse health state while a decrease in score indicates an improvement in health status. Baseline was the most recent recorded value before dosing on Day 1 at schedule visit. Change from Baseline was calculated by subtracting the value on-treatment from the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=101 Participants Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=205 Participants Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Days 28, 84 and 168 Day 28, n=94,199	-0.26 Scores on a scale Standard Error 0.551	-1.75 Scores on a scale Standard Error 0.378
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Days 28, 84 and 168 Day 84, n=87,189	-0.08 Scores on a scale Standard Error 0.594	-2.18 Scores on a scale Standard Error 0.403
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Days 28, 84 and 168 Day 168, n=80,179	-1.32 Scores on a scale Standard Error 0.648	-2.00 Scores on a scale Standard Error 0.434

SECONDARY outcome

Timeframe: Up to Day 169 (Visit 9)

Population: mITT Population

The total number of participants with visits for each type of healthcare contact ( office/practice visits, urgent care/outpatient clinic visits, emergency room visits and the intensive care visit and general wards visit have been presented.

Outcome measures

Outcome measures
Measure	Placebo n=101 Participants Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=205 Participants Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Number of Participants With Healthcare Resource Utilization Status Office/Practice Visits	4 Participants	12 Participants
Number of Participants With Healthcare Resource Utilization Status Urgent Care/Outpatient Clinic Visits	11 Participants	10 Participants
Number of Participants With Healthcare Resource Utilization Status Emergency Room Visits	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to Day 169 (Visit 9)

Population: mITT Population

The total number of days requiring admission to intensive care unit and general ward have been presented.

Outcome measures

Outcome measures
Measure	Placebo n=101 Participants Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=205 Participants Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Number of Days Requiring Admission to Intensive Care Unit and General Ward Days in Intensive Care Unit	0 Days	0 Days
Number of Days Requiring Admission to Intensive Care Unit and General Ward Days in General Ward	35 Days	20 Days

Adverse Events

Placebo

Serious events: 9 serious events

Other events: 32 other events

Deaths: 0 deaths

UMEC 62.5 mcg

Serious events: 17 serious events

Other events: 52 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=101 participants at risk Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=205 participants at risk Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Infections and infestations Upper respiratory tract infection	12.9% 13/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	12.2% 25/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Infections and infestations Nasopharyngitis	10.9% 11/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	9.3% 19/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Infections and infestations Urinary tract infection	3.0% 3/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.98% 2/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Nervous system disorders Dizziness	2.0% 2/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	2.9% 6/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Investigations Blood glucose increased	3.0% 3/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.98% 2/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Reproductive system and breast disorders Benign prostatic hyperplasia	3.0% 3/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.00% 0/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=101 participants at risk Participants received matching placebo to UMEC via ELLIPTA® novel DPI once daily in the morning for the 24-week treatment period.	UMEC 62.5 mcg n=205 participants at risk Participants received UMEC 62.5 mcg via ELLIPTA® DPI once daily in the morning for the 24-week treatment period.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	5.0% 5/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	2.4% 5/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Infections and infestations Pneumonia	0.99% 1/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.98% 2/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Infections and infestations Lung infection	0.99% 1/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.00% 0/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Infections and infestations Pulmonary tuberculosis	0.00% 0/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.49% 1/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
General disorders Chest pain	0.00% 0/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.49% 1/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
General disorders Sudden death	0.00% 0/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.49% 1/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.00% 0/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.49% 1/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Injury, poisoning and procedural complications Concussion	0.99% 1/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.00% 0/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Injury, poisoning and procedural complications Spinal cord injury cervical	0.00% 0/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.49% 1/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Injury, poisoning and procedural complications Subarachnoid haemorrhage	0.00% 0/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.49% 1/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.99% 1/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.49% 1/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.49% 1/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.49% 1/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Cardiac disorders Coronary artery occlusion	0.00% 0/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.49% 1/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Eye disorders Cataract	0.99% 1/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.00% 0/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Gastrointestinal disorders Gastritis	0.00% 0/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.49% 1/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Nervous system disorders Cerebral ischaemia	0.00% 0/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.49% 1/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/101 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.	0.49% 1/205 • AE and nSAE were collected from Day 1 to Day 178 mITT population was used to assess AE and nSAE.