NCT02184611

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

Completed Phase 3 Results posted Last updated 29 June 2020

What this trial tests

Phase 3 trial testing Umeclidinium bromide in Pulmonary Disease, Chronic Obstructive in 308 participants. Completed in 8 November 2017.

Timeline

9 May 2016

Primary endpoint
8 November 2017

8 November 2017

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	308
Start date	9 May 2016
Primary completion	8 November 2017
Estimated completion	8 November 2017
Sites	26 locations across China, South Korea

Drugs / interventions tested

• Umeclidinium bromide — full drug profile →
• Placebo

Conditions studied

• Pulmonary Disease, Chronic Obstructive — all drugs for Pulmonary Disease, Chronic Obstructive →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

40 and older, any sex, with Pulmonary Disease, Chronic Obstructive. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Trough (Pre-bronchodilator) Forced Expiratory Volume in 1 Second (FEV1) on Treatment Day 169 Primary · Baseline (Day 1) and Day 169

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

Group	Value	95% CI
Placebo	-0.022	± 0.0171
UMEC 62.5 mcg	0.131	± 0.0117

Transition Dyspnea Index (TDI) Focal Score at Week 24 (Day 168) Secondary · Week 24 (Day 168)

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 u

Group	Value	95% CI
Placebo	1.6	± 0.26
UMEC 62.5 mcg	2.5	± 0.17

Change From Baseline in Weighted Mean FEV1 Over 0 to 6 Hours Post-dose on Day 1 Secondary · Baseline (pre-dose on Day 1) and Day 1 (0 to 6 hours)

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 ove

Group	Value	95% CI
Placebo	0.011	± 0.0091
UMEC 62.5 mcg	0.136	± 0.0064

Number of Participants With Adverse Events (AE) and Serious AE (SAE) Secondary · Up to Day 178

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.

AE

Group	Value	95% CI
Placebo	56
UMEC 62.5 mcg	122

SAE

Group	Value	95% CI
Placebo	9
UMEC 62.5 mcg	17

Change From Baseline in Vital Sign Parameters: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Secondary · Baseline (Day 1) to Day 169 (Visit 9)

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.

SBP, Anytime post-Baseline

Group	Value	95% CI
Placebo	11.1	± 11.25
UMEC 62.5 mcg	11.4	± 10.64

DBP, Anytime post-Baseline

Group	Value	95% CI
Placebo	-10.2	± 7.55
UMEC 62.5 mcg	-10.8	± 8.03

Change From Baseline in Vital Sign Parameter: Pulse Rate Secondary · Baseline (Day 1) to Day 169 (Visit 9)

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.

Group	Value	95% CI
Placebo	10.7	± 10.94
UMEC 62.5 mcg	8.2	± 9.47

Number of Participants With Electrocardiogram (ECG) Abnormalities Any Time Post Baseline Secondary · Up to Day 169 (Visit 9)

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.

Group	Value	95% CI
Placebo	51
UMEC 62.5 mcg	105

Number of Participants With Hematology Data Outside the Normal Range at Any Time Post-Baseline Secondary · Up to Day 168 (Visit 8)

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 h

Eosinophils, Any time post Baseline, High,n=96,196

Group	Value	95% CI
Placebo	8
UMEC 62.5 mcg	11

Eosinophils, Any time post Baseline, Low,n=96,196

Group	Value	95% CI
Placebo	19
UMEC 62.5 mcg	37

Hematocrit, Any time post Baseline, High,n=96,196

Group	Value	95% CI
Placebo	14
UMEC 62.5 mcg	35

Hematocrit, Any time post Baseline, Low,n=96,196

Group	Value	95% CI
Placebo	3
UMEC 62.5 mcg	21

Hemoglobin, Any time post Baseline, High,n=96,196

Group	Value	95% CI
Placebo	2
UMEC 62.5 mcg	5

Hemoglobin, Any time post Baseline, Low,n=96,196

Group	Value	95% CI
Placebo	7
UMEC 62.5 mcg	28

Lymphocytes, Any time post Baseline, High,n=96,196

Group	Value	95% CI
Placebo	1
UMEC 62.5 mcg	3

Lymphocytes, Any time post Baseline, Low,n=96,196

Group	Value	95% CI
Placebo	3
UMEC 62.5 mcg	10

Number of Participants With Clinical Chemistry Data Outside the Normal Range at Any Time Post-Baseline Secondary · Up to Day 168 (Visit 8)

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 \[

ALT, Any time post Baseline, High

Group	Value	95% CI
Placebo	5
UMEC 62.5 mcg	5

Albumin, Any time post Baseline, High

Group	Value	95% CI
Placebo	0
UMEC 62.5 mcg	1

Albumin, Any time post Baseline, Low

Group	Value	95% CI
Placebo	0
UMEC 62.5 mcg	1

Alkaline Phosphatase, Any time post Baseline, High

Group	Value	95% CI
Placebo	3
UMEC 62.5 mcg	5

Alkaline Phosphatase, Any time post Baseline, Low

Group	Value	95% CI
Placebo	0
UMEC 62.5 mcg	1

AST, Any time post Baseline, High

Group	Value	95% CI
Placebo	0
UMEC 62.5 mcg	3

Calcium, Any time post Baseline, Low

Group	Value	95% CI
Placebo	2
UMEC 62.5 mcg	1

CO2 content,Any time post Baseline, Low

Group	Value	95% CI
Placebo	6
UMEC 62.5 mcg	26

Number of Participants With Abnormal Urinalysis Parameters by Dipstick Method Secondary · Up to Day 168 (Visit 8)

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 categor

Urine Bilirubin, Day 168, 1+

Group	Value	95% CI
Placebo	2
UMEC 62.5 mcg	2

Urine Bilirubin, Day 168, 2+

Group	Value	95% CI
Placebo	1
UMEC 62.5 mcg	0

Urine Glucose, Day 168, 1+

Group	Value	95% CI
Placebo	3
UMEC 62.5 mcg	6

Urine Glucose, Day 168, 2+

Group	Value	95% CI
Placebo	2
UMEC 62.5 mcg	1

Urine Glucose, Day 168, 3+

Group	Value	95% CI
Placebo	2
UMEC 62.5 mcg	2

Urine Glucose, Day 168, Trace

Group	Value	95% CI
Placebo	2
UMEC 62.5 mcg	2

Urine leukocyte esterase, Day 168, 1+

Group	Value	95% CI
Placebo	1
UMEC 62.5 mcg	1

Urine leukocyte esterase, Day 168, 2+

Group	Value	95% CI
Placebo	0
UMEC 62.5 mcg	2

Mean Urine Potential of Hydrogen (pH) Secondary · Day 168 (Visit 8)

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.

Group	Value	95% CI
Placebo	6.16	± 0.520
UMEC 62.5 mcg	6.25	± 0.632

Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Days 28, 84 and 168 Secondary · Baseline (Day 1) and Day 28, Day 84 and Day 168

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 t

Day 28, n=91,188

Group	Value	95% CI
Placebo	-1.45	± 1.174
UMEC 62.5 mcg	-5.84	± 0.813

Day 84, n= 84,183

Group	Value	95% CI
Placebo	-2.46	± 1.268
UMEC 62.5 mcg	-7.05	± 0.860

Day 168, n=78,176

Group	Value	95% CI
Placebo	-4.31	± 1.316
UMEC 62.5 mcg	-7.34	± 0.882

Adverse events — posted to ClinicalTrials.gov

Time frame: AE and nSAE were collected from Day 1 to Day 178. Reporting threshold: 3%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 9/101 (9%)

Deaths: 0/101

UMEC 62.5 mcg

Serious: 17/205 (8%)

Deaths: 1/205

Serious adverse events (18 terms)

Reaction	System	Placebo	UMEC 62.5 mcg
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—
Pneumonia	Infections and infestations	—	—
Lung infection	Infections and infestations	—	—
Pulmonary tuberculosis	Infections and infestations	—	—
Chest pain	General disorders	—	—
Sudden death	General disorders	—	—
Cervical vertebral fracture	Injury, poisoning and procedural complications	—	—
Concussion	Injury, poisoning and procedural complications	—	—
Spinal cord injury cervical	Injury, poisoning and procedural complications	—	—
Subarachnoid haemorrhage	Injury, poisoning and procedural complications	—	—
Type 2 diabetes mellitus	Metabolism and nutrition disorders	—	—
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Coronary artery occlusion	Cardiac disorders	—	—
Cataract	Eye disorders	—	—
Gastritis	Gastrointestinal disorders	—	—
Cerebral ischaemia	Nervous system disorders	—	—
Dermatitis contact	Skin and subcutaneous tissue disorders	—	—

Other adverse events (6 terms — click to expand)

Reaction	System	Placebo	UMEC 62.5 mcg
Upper respiratory tract infection	Infections and infestations	—	—
Nasopharyngitis	Infections and infestations	—	—
Dizziness	Nervous system disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Blood glucose increased	Investigations	—	—
Benign prostatic hyperplasia	Reproductive system and breast disorders	—	—

Most-reported serious reactions: Chronic obstructive pulmonary disease, Pneumonia, Lung infection, Pulmonary tuberculosis, Chest pain, Sudden death, Cervical vertebral fracture, Concussion.

Data from ClinicalTrials.gov NCT02184611 adverse events section.

Sponsor's own description

Studies to date provides substantial evidence for the effectiveness for UMEC 62.5 microgram (mcg) as a long term maintenance therapy for the treatment of COPD; this study further evaluates the efficacy and safety of UMEC 62.5 mcg administered once-daily (OD) for 24 weeks via a NDPI compared with placebo in Asian subjects with COPD. Over approximate 27 weeks of entire study duration, 10 study clinic visits will be conducted on an outpatient basis. Pre-screening visit will be conducted for the informed consent form, review demography, COPD history and COPD concomitant medications. Subjects meeting the eligibility criteria at screening will complete a 7 to 14 day Run-in period and will be provided with albuterol/salbutamol as rescue medication on an "as-needed" basis. Further, subjects will be randomized to the UMEC 62.5 mcg or matching placebo in a 1:2 ratio for 24 week treatment period. A follow up for adverse event assessment will be scheduled approximately 7 days after the treatment period or the Early Withdrawal Visit.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Mechanisms, Pathophysiology and Currently Proposed Treatments of Chronic Obstructive Pulmonary Disease.
   Rodrigues SO, Cunha CMCD, Soares GMV, Silva PL, et al · · 2021 · cited 61× · PMID 34681202 · DOI 10.3390/ph14100979
2. Umeclidinium bromide versus placebo for people with chronic obstructive pulmonary disease (COPD).
   Ni H, Htet A, Moe S. · · 2017 · cited 5× · PMID 28631387 · DOI 10.1002/14651858.cd011897.pub2
3. Efficacy and Safety of Once-Daily Inhaled Umeclidinium in Asian Patients with COPD: Results from a Randomized, Placebo-Controlled Study.
   Zhong N, Zheng J, Lee SH, Lipson DA, et al · · 2020 · cited 3× · PMID 32368027 · DOI 10.2147/copd.s215011