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CompletedNCT03034915Updated Mar 11, 2020Results posted

A 24-week Study to Compare Umeclidinium/Vilanterol (UMEC/VI), UMEC and Salmeterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

A Phase 4 interventional study of UMEC/VI 62.5/25 mcg via ELLIPTA and UMEC 62.5 mcg via ELLIPTA in Pulmonary Disease, Chronic Obstructive, sponsored by GlaxoSmithKline. Completed at 213 sites in 12 countries. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2020-03-11.

Sponsored by GlaxoSmithKline · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
2,696
Allocation
Randomized
Ages
40 Years and older
Sex
All
01

Study summary

COPD is characterized by an airflow limitation, which is not fully reversible, usually progressive and accompanied by chronic cough, sputum production and dyspnea, which can be a major cause of disability and anxiety associated with the disease. In addition, COPD is associated with poor health-related quality of life (HRQoL). Pharmacologic therapy is used to improve lung function, reduce symptoms, reduce the frequency and severity of exacerbations, and also to improve health status and exercise tolerance.

This is a multi-center, randomized, double blind, double dummy, 3-arm parallel group study to compare umeclidinium/vilanterol (62.5/25 microgram [mcg], once daily), umeclidinium (62.5 mcg, once daily), and salmeterol (50 mg, twice daily) in male and female subjects with COPD. The primary purpose of this study is to demonstrate improvements in lung function for subjects treated with UMEC/VI compared with UMEC for 24 weeks.

Approximately 2424 subjects will be randomized across 3 parallel arms in 1:1:1 ratio. Subjects will be stratified based on long-acting bronchodilator usage during the run-in period (none, one or 2 long-acting bronchodilators per day). Subjects will receive either UMEC/VI inhalation powder (62.5/25 microgram [mcg] once daily) administered via the ELLIPTA® dry powder inhaler (DPI) and placebo twice daily via DISKUS® DPI; or UMEC (62.5 mcg once daily) administered via the ELLIPTA DPI and placebo twice daily via DISKUS DPI or salmeterol (50 mcg twice daily [BID]) administered via the DISKUS DPI and placebo once daily via ELLIPTA DPI. The duration of the study will be 29 to 31 weeks including a pre-screening period of 2 weeks, run-in period of 4 weeks, treatment period of 24 weeks and follow-up period of 1 week.

ELLIPTA and DISKUS are trademarks of GSK group of companies.

02

Conditions studied

  • Pulmonary Disease, Chronic Obstructive

Keywords

  • Vilanterol
  • COPD
  • HRQoL
  • Salmeterol
  • Umeclidinium
03

In context

Lung Diseases

3,303 studies on the registry are indexed under Lung Diseases; 355 are open to participants now.

This study's enrollment of 2,696 is above the median of 72 across 2,118 interventional studies indexed under Lung Diseases.

Browse Lung Diseases studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 40 years or older at date of signing informed consent at Screening Visit 1
  • Outpatient with a diagnosis of COPD
  • Persistent airflow limitations as indicated by a pre and post-albuterol/salbutamol FEV1/FVC ratio of \<0.70 and a post-albuterol/salbutamol FEV1 of >=30% to \<=80% predicted normal values at Screening Visit 1.
  • A CAT score of >=10 at Screening Visit 1
  • Current or former cigarette smokers with a history of cigarette smoking of >=10 pack-years (number of pack years = [number of cigarettes per day / 20] multiplied by number of years smoked [e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years both equal 10 pack-years]). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Pipe and/or cigar use cannot be used to calculate pack-year history.
  • Male and female subjects are eligible to participate in the study. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin test), not lactating, and at least one of the following conditions applies: non-reproductive potential defined as pre-menopausal females with documented tubal ligation or documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or hysterectomy or documented bilateral oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases, a blood sample with simultaneous follicle stimulating hormone and estradiol levels consistent with menopause must be tested. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.

A female subject with reproductive potential is eligible to participate if she is not pregnant and agrees to follow one of the highly effective methods for avoiding pregnancy in females of reproductive potential from 30 days prior to the first dose of study medication and until (at least five terminal half-lives or until any continuing pharmacologic effect has ended, whichever is longer) after the last dose of study medication and completion of the follow-up visit. The investigator is responsible for ensuring that subjects understand how to properly use methods of contraception.

  • Capable of giving signed informed consent prior to study participation.

Exclusion criteria

Exclusion criteria

  • A current diagnosis of asthma (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD, which is the primary cause of their respiratory symptoms).
  • Subjects with known alpha-antitrypsin deficiency as the underlying cause of COPD
  • Subjects with active tuberculosis are excluded. Subjects with other respiratory disorders (e.g., clinically significant: bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases) are excluded if these conditions are the primary cause of their respiratory symptoms.
  • Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease as per investigator assessment); stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice, or cirrhosis; chronic stable hepatitis B and C (e.g., presence of hepatitis B surface antigen or positive hepatitis C antibody test result or within 3 months prior to first dose of study treatment) are acceptable if subject otherwise meets entry criteria.
  • Subjects with unstable or life threatening cardiac disease. The investigational product should be used with caution in subjects with severe cardiovascular disease. In the opinion of the investigator, use will only be considered if the benefit is likely to outweigh the risk in conditions such as myocardial infarction or unstable angina in the last 6 months, or unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months, or New York Heart Association Class IV heart failure.
  • The investigator will determine the clinical significance of each abnormal electrocardiogram (ECG) finding in relation to the subject's medical history and exclude subjects who would be at undue risk by participating in the trial. Subjects with the following abnormalities are excluded from participation in the study: atrial fibrillation with rapid ventricular rate >120 beats per minute (bpm), sustained or non-sustained ventricular tachycardia, second degree heart block Mobitz type II or third degree heart block (unless pacemaker or defibrillator had been inserted).
  • Subjects with medical conditions such as narrow-angle glaucoma, urinary retention, prostatic hypertrophy, or bladder neck obstruction will be excluded unless, in the opinion of the study physician, the benefit outweighs the risk.
  • Any subject who is considered unlikely to survive the duration of the study period or has any rapidly progressing disease or immediate life-threatening illness (e.g., cancer). In addition, any subject who has any other condition (e.g., neurological condition) that is likely to affect respiratory function will not be included in the study.
  • Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1. Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least 14 days prior to Screening Visit 1and at least 30 days following the last dose of oral/systemic corticosteroids (if applicable).
  • Subjects who had received inhaled corticosteroids (ICS) or ICS/ long-acting beta-agonist for the treatment of COPD in the 6 weeks prior to Screening Visit1.
  • Subjects who had >1 moderate exacerbation in the 12 months prior to Screening Visit 1, or one severe exacerbation requiring hospitalization in the 12 months prior to Screening Visit 1.
  • Other respiratory tract infections that have not resolved at least 7 days prior to Screening Visit 1.
  • Subjects with lung volume reduction surgery (including procedures such as endobronchial valves) within the 12 months prior to Screening Visit 1.
  • Use of long-term oxygen therapy described as resting oxygen therapy >3 Liter (L)/minute (min) at screening required to maintain adequate oxygenation (e.g., oxygen saturation in arterial blood [SaO2] >90%; oxygen use \<=3 L/min flow is not exclusionary, and subjects may adjust oxygen levels up or down as needed during the study.)
  • Use of ICS within 6 weeks prior to Screening Visit 1; use of depot corticosteroids within 12 weeks prior to Screening Visit 1; use of systemic, oral or parenteral corticosteroids within 6 weeks prior to Screening Visit 1 (Localized corticosteroid injections [e.g., intra-articular and epidural] are permitted); use of antibiotics (for lower respiratory tract infection) within 6 weeks prior to Screening Visit 1; use of phosphodiesterase 4 (PDE4) inhibitor (e.g., roflumilast) within 14 days prior to Screening Visit 1; use of long-acting beta-agonist/ ICS combination products within 6 weeks prior to Screening Visit 1; use of theophyllines within 48 hours prior to Screening Visit 1; use of oral long-acting beta2-agonists within 48 hours and short-acting beta2-agonists within 12 hours prior to Screening Visit 1; use of inhaled short-acting beta2-agonists within 4 hours prior to Screening Visit 1 (use of study provided albuterol/salbutamol is permitted during the study, except in the 4-hour period prior to spirometry testing); use of inhaled short-acting anticholinergics within 4 hours prior to Screening Visit 1; use of inhaled short-acting anticholinergic/short-acting beta2-agonist combination products within 4 hours prior to Screening Visit 1; use of any other investigational medication within 30 days or within 5 drug half-lives (whichever is longer) prior to Screening Visit 1.
  • Subject unable to withhold albuterol/salbutamol for the 4-hour period required prior to spirometry testing at each study visit.
  • Regular use (prescribed for daily/ regular use, not for as-needed use) of short-acting bronchodilators (e.g., albuterol/salbutamol).
  • A known or suspected history of alcohol or drug abuse within 2 years prior to Screening Visit 1 that in the opinion of the investigator would prevent the subject from completing the study procedures.
  • Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, sympathomimetic, lactose/milk protein or magnesium stearate.
  • Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
  • Subject 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.
  • In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete questionnaires on the electronic diary.
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
2,696 participants (actual)

Study arms

  • Experimental
    UMEC/VI 62.5/25 mcg via ELLIPTA + placebo via DISKUS

    Subjects will be instructed to self-administer one dose of UMEC/VI 62.5/25 mcg inhalation powder each morning via ELLIPTA DPI and placebo twice daily (morning and evening) via DISKUS DPI.

    Drug: UMEC/VI 62.5/25 mcg via ELLIPTA · Drug: Placebo via DISKUS

  • Experimental
    UMEC 62.5 mcg via ELLIPTA + placebo via DISKUS

    Subjects will be instructed to self-administer one dose of UMEC 62.5 mcg inhalation powder each morning via ELLIPTA DPI and placebo twice daily (morning and evening) via DISKUS DPI.

    Drug: UMEC 62.5 mcg via ELLIPTA · Drug: Placebo via DISKUS

  • Experimental
    Salmeterol 50 mcg via DISKUS + placebo via ELLIPTA

    Subjects will be instructed to self-administer one dose of salmeterol 50 mcg twice daily (morning and evening) via DISKUS DPI and placebo once daily morning via ELLIPTA DPI.

    Drug: Salmeterol 50 mcg via DISKUS · Drug: Placebo via ELLIPTA

Interventions

  • DrugUMEC/VI 62.5/25 mcg via ELLIPTA

    ELLIPTA DPI inhaler will contain two individual blister strips with 30 blisters per strip; the first strip contains umeclidinium bromide (62.5 mcg per blister) blended with lactose monohydrate and magnesium stearate and second strip contains vilanterol trifenatae (25 mcg per blister) blended with lactose monohydrate and magnesium stearate.

  • DrugUMEC 62.5 mcg via ELLIPTA

    The ELLIPTA inhaler will contain one blister strip, which will have 30 blisters of umeclidinium bromide (62.5 mcg).

  • DrugSalmeterol 50 mcg via DISKUS

    The DISKUS inhaler will contain one blister strip, which will have 60 blisters of salmeterol xinafoate (50 mcg). The DISKUS will provide a total of 60 doses (60 blisters) and will deliver, when actuated, the contents of a single blister strip.

  • DrugPlacebo via ELLIPTA

    Lactose dry powder will be administered using ELLIPTA for both treatment periods. ELLIPTA DPI inhaler will contain two individual blister strips with 30 blisters per strip; containing lactose dry powder.

  • DrugPlacebo via DISKUS

    Lactose dry powder will be administered using DISKUS for both treatment periods. The DISKUS inhaler will contain one blister strip, which will have 60 blisters of lactose dry powder. The DISKUS will provide a total of 60 doses (60 blisters) and will deliver, when actuated, the contents of a single blister strip.

06

What researchers measure

Primary outcomes

  1. Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 24

    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 at Week 24 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on the previous day. Baseline trough FEV1 is the mean of the values measured at 30 minutes and 5 minutes pre-dose on Day 1. Change from Baseline was calculated as the trough FEV1 value on Week 24 minus the Baseline value. Analysis was performed using a repeated measures model (MMRM) with covariates of Baseline FEV1, geographical region, stratum (number of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interaction. ITT population comprised of all randomized participants (excluding those who were randomized in error) who received at least one dose of study medication.

    Time frame: Baseline (Pre-dose on Day 1) and Week 24

Secondary outcomes

  1. Self Administered Computerized (SAC) Transient Dyspnea Index (TDI) Focal Score at Week 24

    TDI focal score comprises of 3 individual scales (Functional Impairment, Magnitude of Task, Magnitude of Effort). Each of these scales had a possible score ranging from -6 to +6, lower scores indicates impairment. TDI focal score was calculated as the sum of 3 individual scores (range is -18 to +18). Lower score indicates deterioration of dyspnea. If a score is missing for any of the three scales, then the TDI focal score was set to missing. Analysis was performed using mixed model repeated measures (MMRM) with covariates of SAC BDI focal score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by SAC BDI and visit by treatment interactions.

    Time frame: Week 24

  2. Percentage of TDI Responders According to SAC TDI Focal Score

    TDI focal score comprises of 3 individual scales (Functional Impairment, Magnitude of Task, Magnitude of Effort). Each of these scales had a possible score ranging from -6 to +6, lower scores indicates impairment. TDI focal score was calculated as the sum of 3 individual scores (range is -18 to +18). Lower score indicates deterioration of dyspnea. If a score is missing for any of the three scales, then TDI focal score was set to missing. A participant was considered as a responder if the on-treatment TDI focal score was at least 1 unit at that visit. Non-response was SAC TDI focal score of less than 1 unit or a missing SAC TDI focal score with no subsequent non-missing on-treatment scores. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and visit, SAC BDI focal score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by SAC BDI and visit by treatment interactions included as covariates.

    Time frame: Week 24

  3. Mean Change From Baseline in Evaluating Respiratory Symptoms (E-RS) Total Score

    The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: respiratory symptoms (RS)-breathlessness (RS-BRL comprised of 5 items, score range \[0-17\]), RS-cough and sputum (RS-CSP comprised of 3 items, score range \[0-11\]), and RS-chest symptoms (RS-CSY comprised of 3 items, score range \[0-12\]). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Baseline E-RS score is the mean within-participant daily score over 7 days prior to randomization. Change from Baseline is the difference at Week 21-Week 24 value and Baseline value. Analysis was performed using MMRM with covariates of Baseline score, geographical region, stratum (no. of bronchodilators per day during run-in), 4-weekly period, treatment, 4-weekly period by Baseline and 4-weekly period by treatment interactions.

    Time frame: Baseline (Pre-dose on Day 1) and Week 21 to Week 24

  4. Mean Change From Baseline in E-RS Subscale Score

    The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: respiratory symptoms (RS)-breathlessness (RS-BRL comprised of 5 items, score range \[0-17\]), RS-cough and sputum (RS-CSP comprised of 3 items, score range \[0-11\]), and RS-chest symptoms (RS-CSY comprised of 3 items, score range \[0-12\]). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Baseline E-RS score is the mean within-participant daily score over 7 days prior to randomization. Change from Baseline is the difference at Week 21-Week 24 value and Baseline value. Analysis was performed using MMRM with covariates of Baseline score, geographical region, stratum (no. of bronchodilators per day during run-in), 4-weekly period, treatment, 4-weekly period by Baseline and 4-weekly period by treatment interactions.

    Time frame: Baseline (Pre-dose on Day 1) and Week 21 to Week 24

  5. Percentage of E-RS Responders According to E-RS Total Score

    The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: RS-BRL comprised of 5 items, score range (0-17); RS-CSP comprised of 3 items, score range (0-11); and RS-CSY comprised of 4 items, score range (0-12). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Response is defined as an E-RS total score of at least 2 or 3.35 below Baseline. Participants with a Baseline but all missing post-Baseline data are also considered a non-responder. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and four-weekly period, Baseline score, stratum (no. of bronchodilators per day during run-in), geographical region, four-weekly period by baseline and four-weekly period by treatment interactions included as covariates.

    Time frame: Week 21 to Week 24

  6. Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score

    SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Baseline is last non-missing score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the value at Week 24. Analysis was performed using mixed model repeated measures (MMRM) with covariates of Baseline SGRQ total score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interactions.

    Time frame: Baseline (Pre-dose on Day 1) and Week 24

  7. Percentage of Responders Based on the Saint (St) George Respiratory Questionnaire COPD Specific (SGRQ) Total Score

    SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and visit, Baseline SGRQ score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by Baseline and visit by treatment interactions included as covariates. Response was defined as an SGRQ total score of 4 or more units below Baseline.

    Time frame: Week 24

  8. Change From Baseline in COPD Assessment Test (CAT)

    The CAT is a participant-completed instrument designed to provide a simple and reliable measure of health status in COPD for the assessment and long-term follow-up of the individual participant. The CAT consists of eight items, each formatted on a differential scale. Participants rated their experience on a 6-point scale for each question, ranging from 0 (no impact) to 5 (high impact). A total CAT score was calculated by summing the non-missing scores on the eight items ranging from 0 to 40 with higher scores indicating greater disease impact. Baseline is defined as the last non-missing score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the value at Week 24. Analysis was performed using mixed model repeated measures (MMRM) with covariates of Baseline CAT score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interactions.

    Time frame: Baseline (Pre-dose on Day 1) and Week 24

  9. Percentage of Responders According to CAT

    The CAT is a participant-completed instrument designed to provide a simple and reliable measure of health status in COPD for the assessment and long-term follow-up of the individual participant. The CAT consists of eight items. Participants rated their experience on a 6-point scale for each question, ranging from 0 (no impact) to 5 (high impact). A total CAT score was calculated by summing the non-missing scores on the eight items ranging from 0 to 40 with higher scores indicate greater disease impact. Response was defined as an CAT score of \>=2 below Baseline. Non response was defined as CAT score \<2 units below Baseline or a missing CAT score with no subsequent on treatment scores. Analysis performed using a generalized linear mixed model with treatment as an explanatory variable and visit, baseline CAT score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by baseline and visit by treatment interactions included as covariates.

    Time frame: Week 24

  10. Number of Participants With on Treatment Adverse Events (AE) and Serious Adverse Events (SAE)

    An 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. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events associated with liver injury and impaired liver function based on pre-defined criteria were categorized as SAE.

    Time frame: Up to Week 24

07

Results

Posted Jul 15, 2019

Participant flow

In this randomized, double-blind, double dummy, 3-arm parallel group study, eligible participants received Umeclidinium/Vilanterol (UMEC/VI) 62.5/25 microgram (mcg) once daily via the ELLIPTA dry powder inhaler (DPI), or UMEC 62.5 mcg once daily via ELLIPTA DPI, or Salmeterol (SAL) 50 mcg twice daily (BID) via the DISKUS DPI (1:1:1) for 24 weeks.

Participant flow — Overall Study
MilestoneUMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+Placebo
Started812804809
Completed717650683
Not completed95154126
Withdrew: Adverse event293222
Withdrew: Lost to follow-up5133
Withdrew: Withdrawal by subject294641
Withdrew: Protocol deviation2147
Withdrew: Lack of efficacy81618
Withdrew: Site closed224
Withdrew: Protocol-defined withdrawal criteria met192629
Withdrew: Physician decision152

Outcome measures

PrimaryChange From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 24

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 at Week 24 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on the previous day. Baseline trough FEV1 is the mean of the values measured at 30 minutes and 5 minutes pre-dose on Day 1. Change from Baseline was calculated as the trough FEV1 value on Week 24 minus the Baseline value. Analysis was performed using a repeated measures model (MMRM) with covariates of Baseline FEV1, geographical region, stratum (number of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interaction. ITT population comprised of all randomized participants (excluding those who were randomized in error) who received at least one dose of study medication.

Time frame:
Baseline (Pre-dose on Day 1) and Week 24
Reported as:
Least squares mean · Liters
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 24
LitersUMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+Placebo
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 240.122 ± 0.00810.056 ± 0.0085-0.019 ± 0.0083
Statistical analysis
  • UMEC/VI 62.5/25 mcg+ Placebo vs UMEC 62.5 mcg + Placebo · Mixed model repeated measures · p = <0.001 · Mean difference (net): 0.066 · 95% CI 0.043 to 0.089LS Mean difference comparing UMEC/VI versus UMEC at Week 24.
  • UMEC/VI 62.5/25 mcg+ Placebo vs Salmeterol 50 mcg+Placebo · Mixed model repeated measures · p = <0.001 · Mean difference (net): 0.141 · 95% CI 0.118 to 0.164LS Mean difference comparing UMEC/VI versus salmeterol at Week 24.
  • UMEC 62.5 mcg + Placebo vs Salmeterol 50 mcg+Placebo · Mixed model repeated measures · p = <0.001 · Mean difference (net): 0.075 · 95% CI 0.051 to 0.098LS Mean difference comparing UMEC versus salmeterol at Week 24.
SecondarySelf Administered Computerized (SAC) Transient Dyspnea Index (TDI) Focal Score at Week 24

TDI focal score comprises of 3 individual scales (Functional Impairment, Magnitude of Task, Magnitude of Effort). Each of these scales had a possible score ranging from -6 to +6, lower scores indicates impairment. TDI focal score was calculated as the sum of 3 individual scores (range is -18 to +18). Lower score indicates deterioration of dyspnea. If a score is missing for any of the three scales, then the TDI focal score was set to missing. Analysis was performed using mixed model repeated measures (MMRM) with covariates of SAC BDI focal score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by SAC BDI and visit by treatment interactions.

Time frame:
Week 24
Reported as:
Least squares mean · Scores on a scale
Self Administered Computerized (SAC) Transient Dyspnea Index (TDI) Focal Score at Week 24
Scores on a scaleUMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+Placebo
Self Administered Computerized (SAC) Transient Dyspnea Index (TDI) Focal Score at Week 241.68 ± 0.1091.30 ± 0.1141.22 ± 0.111
Statistical analysis
  • UMEC/VI 62.5/25 mcg+ Placebo vs UMEC 62.5 mcg + Placebo · Mixed model repeated measures · p = 0.018 · Mean difference (net): 0.37 · 95% CI 0.06 to 0.68LS Mean difference comparing UMEC/VI versus UMEC at Week 24.
  • UMEC/VI 62.5/25 mcg+ Placebo vs Salmeterol 50 mcg+Placebo · Mixed model repeated measures · p = 0.004 · Mean difference (net): 0.45 · 95% CI 0.15 to 0.76LS Mean difference comparing UMEC/VI versus salmeterol at Week 24.
  • UMEC 62.5 mcg + Placebo vs Salmeterol 50 mcg+Placebo · Mixed model repeated measures · p = 0.610 · Mean difference (net): 0.08 · 95% CI -0.23 to 0.39LS Mean difference comparing UMEC versus salmeterol at Week 24
SecondaryPercentage of TDI Responders According to SAC TDI Focal Score

TDI focal score comprises of 3 individual scales (Functional Impairment, Magnitude of Task, Magnitude of Effort). Each of these scales had a possible score ranging from -6 to +6, lower scores indicates impairment. TDI focal score was calculated as the sum of 3 individual scores (range is -18 to +18). Lower score indicates deterioration of dyspnea. If a score is missing for any of the three scales, then TDI focal score was set to missing. A participant was considered as a responder if the on-treatment TDI focal score was at least 1 unit at that visit. Non-response was SAC TDI focal score of less than 1 unit or a missing SAC TDI focal score with no subsequent non-missing on-treatment scores. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and visit, SAC BDI focal score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by SAC BDI and visit by treatment interactions included as covariates.

Time frame:
Week 24
Reported as:
Number · Percentage of responders
Percentage of TDI Responders According to SAC TDI Focal Score
Percentage of respondersUMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+Placebo
Percentage of TDI Responders According to SAC TDI Focal Score504241
Statistical analysis
  • UMEC/VI 62.5/25 mcg+ Placebo vs UMEC 62.5 mcg + Placebo · generalized linear mixed model · p = <0.001 · Odds ratio (or): 1.43 · 95% CI 1.17 to 1.75Odds Ratio (responder vs. a non-responder) comparing UMEC/VI vs UMEC at Week 24
  • UMEC/VI 62.5/25 mcg+ Placebo vs Salmeterol 50 mcg+Placebo · generalized linear mixed model · p = <0.001 · Odds ratio (or): 1.48 · 95% CI 1.21 to 1.81Odds Ratio (responder vs. a non-responder) comparing UMEC/VI versus salmeterol at Week 24
  • UMEC 62.5 mcg + Placebo vs Salmeterol 50 mcg+Placebo · generalized linear mixed model · p = 0.755 · Odds ratio (or): 1.03 · 95% CI 0.84 to 1.27Odds Ratio (responder vs. a non-responder) comparing UMEC versus salmeterol at Week 24.
SecondaryMean Change From Baseline in Evaluating Respiratory Symptoms (E-RS) Total Score

The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: respiratory symptoms (RS)-breathlessness (RS-BRL comprised of 5 items, score range \[0-17\]), RS-cough and sputum (RS-CSP comprised of 3 items, score range \[0-11\]), and RS-chest symptoms (RS-CSY comprised of 3 items, score range \[0-12\]). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Baseline E-RS score is the mean within-participant daily score over 7 days prior to randomization. Change from Baseline is the difference at Week 21-Week 24 value and Baseline value. Analysis was performed using MMRM with covariates of Baseline score, geographical region, stratum (no. of bronchodilators per day during run-in), 4-weekly period, treatment, 4-weekly period by Baseline and 4-weekly period by treatment interactions.

Time frame:
Baseline (Pre-dose on Day 1) and Week 21 to Week 24
Reported as:
Least squares mean · Scores on a scale
Mean Change From Baseline in Evaluating Respiratory Symptoms (E-RS) Total Score
Scores on a scaleUMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+Placebo
Mean Change From Baseline in Evaluating Respiratory Symptoms (E-RS) Total Score-1.52 ± 0.148-0.99 ± 0.152-0.69 ± 0.150
Statistical analysis
  • UMEC/VI 62.5/25 mcg+ Placebo vs UMEC 62.5 mcg + Placebo · Mixed model repeated measures · p = 0.013 · Mean difference (net): -0.53 · 95% CI -0.95 to -0.11LS Mean difference comparing UMEC/VI versus UMEC at Week 21 to Week 24
  • UMEC/VI 62.5/25 mcg+ Placebo vs Salmeterol 50 mcg+Placebo · Mixed model repeated measures · p = <0.001 · Mean difference (net): -0.83 · 95% CI -1.25 to -0.42LS Mean difference comparing UMEC/VI versus salmeterol at Week 21 to Week 24..
  • UMEC 62.5 mcg + Placebo vs Salmeterol 50 mcg+Placebo · Mixed model repeated measures · p = 0.159 · Mean difference (net): -0.30 · 95% CI -0.72 to 0.12LS Mean difference comparing UMEC versus salmeterol at Week 21 to Week 24
SecondaryMean Change From Baseline in E-RS Subscale Score

The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: respiratory symptoms (RS)-breathlessness (RS-BRL comprised of 5 items, score range \[0-17\]), RS-cough and sputum (RS-CSP comprised of 3 items, score range \[0-11\]), and RS-chest symptoms (RS-CSY comprised of 3 items, score range \[0-12\]). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Baseline E-RS score is the mean within-participant daily score over 7 days prior to randomization. Change from Baseline is the difference at Week 21-Week 24 value and Baseline value. Analysis was performed using MMRM with covariates of Baseline score, geographical region, stratum (no. of bronchodilators per day during run-in), 4-weekly period, treatment, 4-weekly period by Baseline and 4-weekly period by treatment interactions.

Time frame:
Baseline (Pre-dose on Day 1) and Week 21 to Week 24
Reported as:
Least squares mean · Scores on a scale
Mean Change From Baseline in E-RS Subscale Score
Scores on a scaleUMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+Placebo
RS-BRL-0.67 ± 0.080-0.40 ± 0.082-0.22 ± 0.081
RS-CSP-0.45 ± 0.044-0.38 ± 0.045-0.32 ± 0.044
RS-CSY-0.39 ± 0.049-0.22 ± 0.050-0.15 ± 0.049
Statistical analysis
  • UMEC/VI 62.5/25 mcg+ Placebo vs UMEC 62.5 mcg + Placebo · Mixed model repeated measures · p = 0.016 (E-RS Breathlessness Score) · Mean difference (net): -0.27 · 95% CI -0.50 to -0.05LS Mean difference comparing UMEC/VI versus UMEC at Week 21 to Week 24.
  • UMEC/VI 62.5/25 mcg+ Placebo vs Salmeterol 50 mcg+Placebo · Mixed model repeated measures · p = <0.001 (E-RS Breathlessness Score) · Mean difference (net): -0.46 · 95% CI -0.68 to -0.23LS Mean difference comparing UMEC/VI versus salmeterol at Week 21 to Week 24.
  • UMEC 62.5 mcg + Placebo vs Salmeterol 50 mcg+Placebo · Mixed model repeated measures · p = 0.115 (E-RS Breathlessness Score) · Mean difference (net): -0.18 · 95% CI -0.41 to 0.04LS Mean difference comparing UMEC versus salmeterol at Week 21 to Week 24.
  • UMEC/VI 62.5/25 mcg+ Placebo vs UMEC 62.5 mcg + Placebo · Mixed model repeated measures · p = 0.247 (E-RS Cough and Sputum Score) · Mean difference (net): -0.07 · 95% CI -0.20 to 0.05LS Mean difference comparing UMEC/VI versus UMEC at Week 21 to Week 24.
  • UMEC/VI 62.5/25 mcg+ Placebo vs Salmeterol 50 mcg+Placebo · Mixed model repeated measures · p = 0.042 (E-RS Cough and Sputum Score) · Mean difference (net): -0.13 · 95% CI -0.25 to 0.00LS Mean difference comparing UMEC/VI versus salmeterol at Week 21 to Week 24.
  • UMEC 62.5 mcg + Placebo vs Salmeterol 50 mcg+Placebo · Mixed model repeated measures · p = 0.391 (E-RS Cough and Sputum Score) · Mean difference (net): -0.05 · 95% CI -0.18 to 0.07LS Mean difference comparing UMEC versus salmeterol at Week 21 to Week 24.
  • UMEC/VI 62.5/25 mcg+ Placebo vs UMEC 62.5 mcg + Placebo · Mixed model repeated measures · p = 0.014 (E-RS Chest Symptoms Score) · Mean difference (net): -0.17 · 95% CI -0.31 to -0.04LS Mean difference comparing UMEC/VI versus UMEC at Week 21 to Week 24
  • UMEC/VI 62.5/25 mcg+ Placebo vs Salmeterol 50 mcg+Placebo · Mixed model repeated measures · p = <0.001 (E-RS Chest Symptoms Score) · Mean difference (net): -0.24 · 95% CI -0.37 to -0.10LS Mean difference comapring UMEC/VI versus salmeterol at Week 21 to Week 24.
  • UMEC 62.5 mcg + Placebo vs Salmeterol 50 mcg+Placebo · Mixed model repeated measures · p = 0.340 (E-RS Chest Symptoms Score) · Mean difference (net): -0.07 · 95% CI -0.20 to 0.07LS Mean difference comparing UMEC versus salmeterol at Week 21 to Week 24.
SecondaryPercentage of E-RS Responders According to E-RS Total Score

The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: RS-BRL comprised of 5 items, score range (0-17); RS-CSP comprised of 3 items, score range (0-11); and RS-CSY comprised of 4 items, score range (0-12). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Response is defined as an E-RS total score of at least 2 or 3.35 below Baseline. Participants with a Baseline but all missing post-Baseline data are also considered a non-responder. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and four-weekly period, Baseline score, stratum (no. of bronchodilators per day during run-in), geographical region, four-weekly period by baseline and four-weekly period by treatment interactions included as covariates.

Time frame:
Week 21 to Week 24
Reported as:
Number · Percentage of responders
Percentage of E-RS Responders According to E-RS Total Score
Percentage of respondersUMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+Placebo
Percentage of E-RS Responders According to E-RS Total Score362727
Statistical analysis
  • UMEC/VI 62.5/25 mcg+ Placebo vs UMEC 62.5 mcg + Placebo · generalized linear mixed model · p = <0.001 · Odds ratio (or): 1.52 · 95% CI 1.22 to 1.89Odds Ratio (responder vs. a non-responder) comparing UMEC/VI vs UMEC at Week 21 to Week 24
  • UMEC/VI 62.5/25 mcg+ Placebo vs Salmeterol 50 mcg+Placebo · generalized linear mixed model · p = <0.001 · Odds ratio (or): 1.53 · 95% CI 1.23 to 1.90Odds Ratio (responder vs. a non-responder) comparing UMEC/VI versus salmeterol at Week 21 to Week 24.
  • UMEC 62.5 mcg + Placebo vs Salmeterol 50 mcg+Placebo · generalized linear mixed model · p = 0.969 · Odds ratio (or): 1.00 · 95% CI 0.80 to 1.26Odds Ratio (responder vs. a non-responder) comparing UMEC versus salmeterol at Week 21 to Week 24.
SecondaryChange From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score

SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Baseline is last non-missing score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the value at Week 24. Analysis was performed using mixed model repeated measures (MMRM) with covariates of Baseline SGRQ total score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interactions.

Time frame:
Baseline (Pre-dose on Day 1) and Week 24
Reported as:
Least squares mean · Scores on a scale
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score
Scores on a scaleUMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+Placebo
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score-4.98 ± 0.465-5.23 ± 0.484-3.29 ± 0.475
Statistical analysis
  • UMEC/VI 62.5/25 mcg+ Placebo vs UMEC 62.5 mcg + Placebo · mixed model repeated measure · p = 0.709 · Mean difference (net): 0.25 · 95% CI -1.07 to 1.57LS Mean difference comparing UMEC/VI versus UMEC at Week 24.
  • UMEC/VI 62.5/25 mcg+ Placebo vs Salmeterol 50 mcg+Placebo · mixed model repeated measure · p = 0.011 · Mean difference (net): -1.69 · 95% CI -2.99 to -0.39LS Mean difference comparing UMEC/VI versus salmeterol at Week 24.
  • UMEC 62.5 mcg + Placebo vs Salmeterol 50 mcg+Placebo · mixed model repeated measure · p = 0.004 · Mean difference (net): -1.94 · 95% CI -3.27 to -0.61LS Mean difference comparing UMEC versus salmeterol at Week 24.
SecondaryPercentage of Responders Based on the Saint (St) George Respiratory Questionnaire COPD Specific (SGRQ) Total Score

SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and visit, Baseline SGRQ score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by Baseline and visit by treatment interactions included as covariates. Response was defined as an SGRQ total score of 4 or more units below Baseline.

Time frame:
Week 24
Reported as:
Number · Percentage of responders
Percentage of Responders Based on the Saint (St) George Respiratory Questionnaire COPD Specific (SGRQ) Total Score
Percentage of respondersUMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+Placebo
Percentage of Responders Based on the Saint (St) George Respiratory Questionnaire COPD Specific (SGRQ) Total Score454136
Statistical analysis
  • UMEC/VI 62.5/25 mcg+ Placebo vs UMEC 62.5 mcg + Placebo · generalized linear mixed model · p = 0.063 · Odds ratio (or): 1.21 · 95% CI 0.99 to 1.48Odds Ratio (responder vs. a non-responder) comparing UMEC/VI versus UMEC at Week 24.
  • UMEC/VI 62.5/25 mcg+ Placebo vs Salmeterol 50 mcg+Placebo · generalized linear mixed model · p = <0.001 · Odds ratio (or): 1.49 · 95% CI 1.22 to 1.83Odds Ratio (responder vs. a non-responder) comparing UMEC/VI versus salmeterol at Week 24.
  • UMEC 62.5 mcg + Placebo vs Salmeterol 50 mcg+Placebo · generalized linear mixed model · p = 0.045 · Odds ratio (or): 1.23 · 95% CI 1.00 to 1.51Odds Ratio (responder vs. a non-responder) comparing UMEC versus salmeterol at Week 24.
SecondaryChange From Baseline in COPD Assessment Test (CAT)

The CAT is a participant-completed instrument designed to provide a simple and reliable measure of health status in COPD for the assessment and long-term follow-up of the individual participant. The CAT consists of eight items, each formatted on a differential scale. Participants rated their experience on a 6-point scale for each question, ranging from 0 (no impact) to 5 (high impact). A total CAT score was calculated by summing the non-missing scores on the eight items ranging from 0 to 40 with higher scores indicating greater disease impact. Baseline is defined as the last non-missing score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the value at Week 24. Analysis was performed using mixed model repeated measures (MMRM) with covariates of Baseline CAT score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interactions.

Time frame:
Baseline (Pre-dose on Day 1) and Week 24
Reported as:
Least squares mean · Scores on a scale
Change From Baseline in COPD Assessment Test (CAT)
Scores on a scaleUMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+Placebo
Change From Baseline in COPD Assessment Test (CAT)-3.5 ± 0.21-3.4 ± 0.22-2.9 ± 0.21
Statistical analysis
  • UMEC/VI 62.5/25 mcg+ Placebo vs UMEC 62.5 mcg + Placebo · mixed model repeated measures · p = 0.891 · Mean difference (net): 0.0 · 95% CI -0.6 to 0.6LS Mean difference comparing UMEC/VI versus UMEC at Week 24.
  • UMEC/VI 62.5/25 mcg+ Placebo vs Salmeterol 50 mcg+Placebo · mixed model repeated measures · p = 0.074 · Mean difference (net): -0.5 · 95% CI -1.1 to 0.1LS Mean difference comparing UMEC/VI versus salmeterol at Week 24.
  • UMEC 62.5 mcg + Placebo vs Salmeterol 50 mcg+Placebo · mixed model repeated measures · p = 0.107 · Odds ratio (or): -0.5 · 95% CI -1.1 to 0.1LS Mean difference comparing UMEC versus salmeterol at Week 24.
SecondaryPercentage of Responders According to CAT

The CAT is a participant-completed instrument designed to provide a simple and reliable measure of health status in COPD for the assessment and long-term follow-up of the individual participant. The CAT consists of eight items. Participants rated their experience on a 6-point scale for each question, ranging from 0 (no impact) to 5 (high impact). A total CAT score was calculated by summing the non-missing scores on the eight items ranging from 0 to 40 with higher scores indicate greater disease impact. Response was defined as an CAT score of \>=2 below Baseline. Non response was defined as CAT score \<2 units below Baseline or a missing CAT score with no subsequent on treatment scores. Analysis performed using a generalized linear mixed model with treatment as an explanatory variable and visit, baseline CAT score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by baseline and visit by treatment interactions included as covariates.

Time frame:
Week 24
Reported as:
Number · Percentage of responders
Percentage of Responders According to CAT
Percentage of respondersUMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+Placebo
Percentage of Responders According to CAT554850
Statistical analysis
  • UMEC/VI 62.5/25 mcg+ Placebo vs UMEC 62.5 mcg + Placebo · generalized linear mixed model · p = 0.003 · Odds ratio (or): 1.35 · 95% CI 1.11 to 1.65Odds Ratio (responder vs. a non-responder) comparing UMEC/VI versus UMEC at Week 24.
  • UMEC/VI 62.5/25 mcg+ Placebo vs Salmeterol 50 mcg+Placebo · generalized linear mixed model · p = 0.037 · Odds ratio (or): 1.23 · 95% CI 1.01 to 1.50Odds Ratio (responder vs. a non-responder) comparing UMEC/VI versus salmeterol at Week 24.
  • UMEC 62.5 mcg + Placebo vs Salmeterol 50 mcg+Placebo · generalized linear mixed model · p = 0.363 · Odds ratio (or): 0.91 · 95% CI 0.75 to 1.11Odds Ratio (responder vs. a non-responder) comparing UMEC versus salmeterol at Week 24.
SecondaryNumber of Participants With on Treatment Adverse Events (AE) and Serious Adverse Events (SAE)

An 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. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events associated with liver injury and impaired liver function based on pre-defined criteria were categorized as SAE.

Time frame:
Up to Week 24
Reported as:
Number · Participants
Number of Participants With on Treatment Adverse Events (AE) and Serious Adverse Events (SAE)
ParticipantsUMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+Placebo
Any AE315316314
Any SAE493538

Adverse events

Collected over On-Treatment serious adverse events (SAEs) and non-serious AEs (nSAEs) were collected from start of study treatment until Week 24.. Non-serious events are listed at a 3% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
UMEC/VI 62.5/25 mcg+ Placebo4/812 (0.5%)49/812 (6%)68/812 (8.4%)
UMEC 62.5 mcg + Placebo4/804 (0.5%)35/804 (4.4%)87/804 (10.8%)
Salmeterol 50 mcg+Placebo0/809 (0%)38/809 (4.7%)84/809 (10.4%)
Most frequent serious events
Showing 10 of 93
Most frequent serious events
EventUMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+Placebo
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders7/8127/8049/809
PneumoniaInfections and infestations4/8124/8045/809
Coronary artery diseaseCardiac disorders1/8122/8040/809
Peripheral arterial occlusive diseaseVascular disorders1/8122/8041/809
Atrial fibrillationCardiac disorders2/8121/8042/809
SepsisInfections and infestations2/8120/8040/809
Small intestinal obstructionGastrointestinal disorders2/8120/8040/809
HaematomaVascular disorders2/8120/8040/809
Rotator cuff syndromeMusculoskeletal and connective tissue disorders2/8120/8040/809
PneumothoraxRespiratory, thoracic and mediastinal disorders0/8121/8041/809
Most frequent other events
Most frequent other events
EventUMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+Placebo
NasopharyngitisInfections and infestations68/81287/80484/809

Baseline characteristics

Age, Continuous
Age, Continuous(Years)UMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+PlaceboTotal
Mean64.6 ± 8.3764.9 ± 8.4864.4 ± 8.5364.6 ± 8.46
Sex: Female, Male
Sex: Female, Male(Participants)UMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+PlaceboTotal
Female319327342988
Male4934774671437
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)UMEC/VI 62.5/25 mcg+ PlaceboUMEC 62.5 mcg + PlaceboSalmeterol 50 mcg+PlaceboTotal
Black or African American24232572
American Indian or Alaska Native13121237
Asian - Central/South Asian Heritage5005
Asian - Japanese Heritage0101
Asian - East Asian Heritage0011
White - Arabic/North African Heritage3115
White - White/Caucasian/European Heritage7647637652292
American Indian or Alaska Native & White1001
Black or African American & White24410
Native Hawaiian or other Pacific Islander & White0011
08

Study locations

213 sites
  • GSK Investigational Site
    Phoenix, Arizona 85018, United States
  • GSK Investigational Site
    Lincoln, California 95648, United States
  • GSK Investigational Site
    Clearwater, Florida 33765, United States
  • GSK Investigational Site
    Orlando, Florida 32825, United States
  • GSK Investigational Site
    Tampa, Florida 33603, United States
  • GSK Investigational Site
    O'Fallon, Illinois 62269, United States
  • GSK Investigational Site
    Natchitoches, Louisiana 71457, United States
  • GSK Investigational Site
    Edina, Minnesota 55435, United States
  • GSK Investigational Site
    Fridley, Minnesota 55432, United States
  • GSK Investigational Site
    Minneapolis, Minnesota 55407, United States
  • GSK Investigational Site
    Woodbury, Minnesota 55125, United States
  • GSK Investigational Site
    Chesterfield, Missouri 63017, United States
  • GSK Investigational Site
    Saint Charles, Missouri 63301, United States
  • GSK Investigational Site
    Saint Louis, Missouri 63141, United States
  • GSK Investigational Site
    Omaha, Nebraska 68134, United States
  • GSK Investigational Site
    Albuquerque, New Mexico 87108, United States
  • GSK Investigational Site
    Charlotte, North Carolina 28207, United States
  • GSK Investigational Site
    Gastonia, North Carolina 28054, United States
  • GSK Investigational Site
    Monroe, North Carolina 28112, United States
  • GSK Investigational Site
    Mooresville, North Carolina 28117, United States
  • GSK Investigational Site
    Winston-Salem, North Carolina 27103, United States
  • GSK Investigational Site
    Cincinnati, Ohio 45231, United States
  • GSK Investigational Site
    Medford, Oregon 97504, United States
  • GSK Investigational Site
    Anderson, South Carolina 29621, United States
  • GSK Investigational Site
    Charleston, South Carolina 29406-7108, United States
  • GSK Investigational Site
    Easley, South Carolina 29640, United States
  • GSK Investigational Site
    Gaffney, South Carolina 29340, United States
  • GSK Investigational Site
    Greenville, South Carolina 29615, United States
  • GSK Investigational Site
    Lancaster, South Carolina 29720, United States
  • GSK Investigational Site
    Mount Pleasant, South Carolina 29464, United States
  • GSK Investigational Site
    Rock Hill, South Carolina 29732, United States
  • GSK Investigational Site
    Seneca, South Carolina 29678, United States
  • GSK Investigational Site
    Spartanburg, South Carolina 29303, United States
  • GSK Investigational Site
    Union, South Carolina 29379, United States
  • GSK Investigational Site
    Sherman, Texas 75092, United States
  • GSK Investigational Site
    Abingdon, Virginia 24210, United States
  • GSK Investigational Site
    Morgantown, West Virginia 26505, United States
  • GSK Investigational Site
    Ciudad Autonoma de Buenos Aires, Buenos Aires C1028AAP, Argentina
  • GSK Investigational Site
    Ciudad Autonoma de Buenos Aires, Buenos Aires C1414AIF, Argentina
  • GSK Investigational Site
    Ciudad Autonoma de Buenos Aires, Buenos Aires C1425AGC, Argentina
  • GSK Investigational Site
    Florida, Buenos Aires 1602, Argentina
  • GSK Investigational Site
    La Plata, Buenos Aires, Argentina
  • GSK Investigational Site
    Lobos, Buenos Aires 7240, Argentina
  • GSK Investigational Site
    Mar del Plata, Buenos Aires 7600, Argentina
  • GSK Investigational Site
    Mar del Plata, Buenos Aires B7600FZN, Argentina
  • GSK Investigational Site
    Paraná, Buenos Aires E3100BHK, Argentina
  • GSK Investigational Site
    Quilmes, Buenos Aires B1878FNR, Argentina
  • GSK Investigational Site
    Vicente Lopez, Buenos Aires B1602DOH, Argentina
  • GSK Investigational Site
    Cordoba, Córdova X5003DCE, Argentina
  • GSK Investigational Site
    Concepcion del Uruguay, Entre Ríos 3260, Argentina
  • GSK Investigational Site
    San Rafael, Mendoza 5600, Argentina
  • GSK Investigational Site
    Rosario, Santa Fe 2000, Argentina
  • GSK Investigational Site
    Rosario, Santa Fe S2002OJN, Argentina
  • GSK Investigational Site
    Buenos Aires, C1120AAC, Argentina
  • GSK Investigational Site
    Buenos Aires, C1424BSF, Argentina
  • GSK Investigational Site
    Buenos Aires, C1425BEN, Argentina
  • GSK Investigational Site
    Capital Federal, C1440BRR, Argentina
  • GSK Investigational Site
    Ciudad Autonoma de Buenis Aires, C1015ABR, Argentina
  • GSK Investigational Site
    Ciudad Autónoma de Buenos Aires, C1121ABE, Argentina
  • GSK Investigational Site
    Ciudad Autónoma de Buenos Aires, C1128AAF, Argentina
  • GSK Investigational Site
    Ciudad Autónoma de Buenos Aires, C1426ABP, Argentina
  • GSK Investigational Site
    Mendoza, 5500, Argentina
  • GSK Investigational Site
    Mendoza, 5501, Argentina
  • GSK Investigational Site
    Mendoza, M5500CCG, Argentina
  • GSK Investigational Site
    Monte Grande, 1842, Argentina
  • GSK Investigational Site
    San Miguel de Tucumán, 4000, Argentina
  • GSK Investigational Site
    Santa Fe, 3000, Argentina
  • GSK Investigational Site
    Santa Rosa, 6300, Argentina
  • GSK Investigational Site
    Tucumán, T4000DGF, Argentina
  • GSK Investigational Site
    Coffs Harbour, New South Wales 2450, Australia
  • GSK Investigational Site
    Darlinghurst, Sydney, New South Wales 2010, Australia
  • GSK Investigational Site
    Kanwal, New South Wales 2259, Australia
  • GSK Investigational Site
    Port Macquarie, New South Wales 2444, Australia
  • GSK Investigational Site
    Sydney, New South Wales 2010, Australia
  • GSK Investigational Site
    Moncton, New Brunswick E1G1A7, Canada
  • GSK Investigational Site
    Truro, Nova Scotia B2N 1L2, Canada
  • GSK Investigational Site
    Hamilton, Ontario L8L 5G8, Canada
  • GSK Investigational Site
    London, Ontario N5W 6A2, Canada
  • GSK Investigational Site
    Sarnia, Ontario N7T 4X3, Canada
  • GSK Investigational Site
    Toronto, Ontario M9V 4B4, Canada
  • GSK Investigational Site
    Windsor, Ontario N8X 1T3, Canada
  • GSK Investigational Site
    Gatineau, Quebec J8Y 6S8, Canada
  • GSK Investigational Site
    Mirabel, Quebec J7J 2K8, Canada
  • GSK Investigational Site
    Montréal, Quebec H1M 1B1, Canada
  • GSK Investigational Site
    St. Charles-Borromee, Quebec J6E 2B4, Canada
  • GSK Investigational Site
    Quebec, G1V 4G5, Canada
  • GSK Investigational Site
    Quebec, G1W 4R4, Canada
  • GSK Investigational Site
    Marseille cedex 03, 13331, France
  • GSK Investigational Site
    Nice, 06000, France
  • GSK Investigational Site
    Perpignan, 66000, France
  • GSK Investigational Site
    Pessac cedex, 33604, France
  • GSK Investigational Site
    Karlsruhe, Baden-Wuerttemberg 76137, Germany
  • GSK Investigational Site
    Wiesloch, Baden-Wuerttemberg 69168, Germany
  • GSK Investigational Site
    Bamberg, Bayern 96049, Germany
  • GSK Investigational Site
    Erlangen, Bayern 91052, Germany
  • GSK Investigational Site
    Muenchen, Bayern 80339, Germany
  • GSK Investigational Site
    Muenchen, Bayern 81241, Germany
  • GSK Investigational Site
    Potsdam, Brandenburg 14469, Germany
  • GSK Investigational Site
    Ruedersdorf, Brandenburg 15562, Germany
  • GSK Investigational Site
    Darmstadt, Hessen 64283, Germany

Showing the first 100 of 213 sites across 12 countries.

09

References and documents

Publications

  • Maltais F, Bjermer L, Kerwin EM, Jones PW, Watkins ML, Tombs L, Naya IP, Boucot IH, Lipson DA, Compton C, Vahdati-Bolouri M, Vogelmeier CF. Efficacy of umeclidinium/vilanterol versus umeclidinium and salmeterol monotherapies in symptomatic patients with COPD not receiving inhaled corticosteroids: the EMAX randomised trial. Respir Res. 2019 Oct 30;20(1):238. doi: 10.1186/s12931-019-1193-9. PubMed 31666084 ↗
  • Bjermer LH, Boucot IH, Vogelmeier CF, Maltais F, Jones PW, Tombs L, Compton C, Lipson DA, Kerwin EM. Efficacy and Safety of Umeclidinium/Vilanterol in Current and Former Smokers with COPD: A Prespecified Analysis of The EMAX Trial. Adv Ther. 2021 Sep;38(9):4815-4835. doi: 10.1007/s12325-021-01855-y. Epub 2021 Aug 4. PubMed 34347255 ↗
  • Maltais F, Naya IP, Vogelmeier CF, Boucot IH, Jones PW, Bjermer L, Tombs L, Compton C, Lipson DA, Kerwin EM. Salbutamol use in relation to maintenance bronchodilator efficacy in COPD: a prospective subgroup analysis of the EMAX trial. Respir Res. 2020 Oct 22;21(1):280. doi: 10.1186/s12931-020-01451-8. PubMed 33092591 ↗
  • Kerwin EM, Boucot IH, Vogelmeier CF, Maltais F, Naya IP, Tombs L, Jones PW, Lipson DA, Keeley T, Bjermer L. Early and sustained symptom improvement with umeclidinium/vilanterol versus monotherapy in COPD: a post hoc analysis of the EMAX randomised controlled trial. Ther Adv Respir Dis. 2020 Jan-Dec;14:1753466620926949. doi: 10.1177/1753466620926949. PubMed 32462979 ↗

Study documents

  • Study protocol · Apr 18, 2017
  • Statistical analysis plan · Jul 18, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — IPD for this study will be made available via the Clinical Study Data Request site.

Supporting information: Study protocol, Sap, Icf, Csr

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 11, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03034915
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
Jan 27, 2017
Start date
Jun 16, 2017
Primary completion
Jun 18, 2018
Completion
Jun 18, 2018
Results posted
Jul 15, 2019
Last update
Mar 11, 2020

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2020. You cannot join it, but the record below documents what was studied.

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