Last updated: 07/17/2024 17:12:23
A 24-week study to compare Umeclidinium/Vilanterol (UMEC/VI), UMEC and salmeterol in subjects with chronic obstructive pulmonary disease (COPD)
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A 24-week treatment, multi-center, randomized, double-blind, double-dummy, parallel group study to compare Umeclidinium/Vilanterol, Umeclidinium, and Salmeterol in subjects with chronic obstructive pulmonary disease (COPD)
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Allocation:
Randomized
Primary outcomes:
Change from Baseline in trough forced expiratory volume in one second (FEV1)
Timeframe: Baseline and Week 24
Secondary outcomes:
Change from Baseline in self-administered computerised (SAC) transient dyspnea index (TDI)
Timeframe: Baseline and at Week 4, Week 12 and Week 24
Number of TDI responders according to SAC TDI score
Timeframe: Up to 24 weeks
Total scores of respiratory Symptoms (E-RS)-COPD and its subscales: breathlessness, cough and sputum and chest symptoms
Timeframe: Up to 24 weeks
Number of E-RS responders according to E-RS score
Timeframe: Up to 24 weeks
Change from Baseline in St George’s respiratory questionnaire-chronic obstructive pulmonary disease specific (SGRQ-C)
Timeframe: Baseline and at Week 4, Week 12 and Week 24
Number of responders according to SGRQ-C total score
Timeframe: Week 4, Week 12 and Week 24
Change from Baseline in COPD assessment test (CAT)
Timeframe: Baseline and at Week 4, Week 12 and Week 24
Number of responders according to CAT
Timeframe: Week 4, Week 12 and Week 24
Interventions:
Drug: UMEC/VI 62.5/25 mcg via ELLIPTA
Drug: UMEC 62.5 mcg via ELLIPTA
Drug: Salmeterol 50 mcg via DISKUS
Drug: Placebo via ELLIPTA
Drug: Placebo via DISKUS
Enrollment:
2696
Observational study model:
Not applicable
Primary completion date:
2018-18-06
Time perspective:
Not applicable
Clinical 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;20:238
Medical condition
Pulmonary Disease, Chronic Obstructive
Product
salmeterol, umeclidinium bromide, umeclidinium bromide/vilanterol, vilanterol
Collaborators
Not applicable
Study date(s)
June 2017 to June 2018
Type
Interventional
Phase
4
Participation criteria
Sex
Female & Male
Age
40+ years
Accepts healthy volunteers
No
- Inclusion Criteria
- 40 years or older at date of signing informed consent at Screening Visit 1
Inclusion and exclusion criteria
Inclusion criteria:
- 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
- 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.
Trial location(s)
Location
GSK Investigational Site
Abingdon, Virginia, United States, 24210
Status
Study Complete
Location
GSK Investigational Site
Albuquerque, New Mexico, United States, 87108
Status
Study Complete
Location
GSK Investigational Site
Anderson, South Carolina, United States, 29621
Status
Study Complete
Location
GSK Investigational Site
Bergisch Gladbach, Nordrhein-Westfalen, Germany, 51429
Status
Study Complete
Location
GSK Investigational Site
Bochum, Nordrhein-Westfalen, Germany, 44787
Status
Study Complete
Location
GSK Investigational Site
Bonn, Nordrhein-Westfalen, Germany, 53119
Status
Study Complete
Location
GSK Investigational Site
Bonn, Nordrhein-Westfalen, Germany, 53123
Status
Study Complete
Location
GSK Investigational Site
Buenos Aires, Buenos Aires, Argentina, C1120AAC
Status
Study Complete
Location
GSK Investigational Site
Cassano delle Murge (BA), Puglia, Italy, 70020
Status
Study Complete
Location
GSK Investigational Site
Charleston, South Carolina, United States, 29406-7108
Status
Study Complete
Location
GSK Investigational Site
Charlotte, North Carolina, United States, 28207
Status
Study Complete
Location
GSK Investigational Site
Chesterfield, Missouri, United States, 63017
Status
Study Complete
Location
GSK Investigational Site
Cincinnati, Ohio, United States, 45231
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autonoma de Buenis Aires, Argentina, C1015ABR
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1028AAP
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, C1121ABE
Status
Study Complete
Location
GSK Investigational Site
Clearwater, Florida, United States, 33765
Status
Study Complete
Location
GSK Investigational Site
Coffs Harbour, New South Wales, Australia, 2450
Status
Study Complete
Location
GSK Investigational Site
Concepcion del Uruguay, Entre Ríos, Argentina, 3260
Status
Study Complete
Location
GSK Investigational Site
Darlinghurst, Sydney, New South Wales, Australia, 2010
Status
Study Complete
Location
GSK Investigational Site
Dortmund, Nordrhein-Westfalen, Germany, 44263
Status
Study Complete
Location
GSK Investigational Site
Dueren, Nordrhein-Westfalen, Germany, 52349
Status
Study Complete
Location
GSK Investigational Site
Easley, South Carolina, United States, 29640
Status
Study Complete
Location
GSK Investigational Site
Edina, Minnesota, United States, 55435
Status
Study Complete
Location
GSK Investigational Site
Eloffsdal, Gauteng, South Africa, 0084
Status
Study Complete
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45355
Status
Study Complete
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45359
Status
Study Complete
Location
GSK Investigational Site
Florida, Buenos Aires, Argentina, 1602
Status
Study Complete
Location
GSK Investigational Site
Frankfurt am Main, Hessen, Germany, 60596
Status
Study Complete
Location
GSK Investigational Site
Fridley, Minnesota, United States, 55432
Status
Study Complete
Location
GSK Investigational Site
Gaffney, South Carolina, United States, 29340
Status
Study Complete
Location
GSK Investigational Site
Gastonia, North Carolina, United States, 28054
Status
Study Complete
Location
GSK Investigational Site
Geesthacht, Schleswig-Holstein, Germany, 21502
Status
Study Complete
Location
GSK Investigational Site
Gelsenkirchen, Nordrhein-Westfalen, Germany, 45879
Status
Study Complete
Location
GSK Investigational Site
Greenville, South Carolina, United States, 29615
Status
Study Complete
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30159
Status
Study Complete
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30167
Status
Study Complete
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30173
Status
Study Complete
Location
GSK Investigational Site
Johannesburg, Gauteng, South Africa, 2113
Status
Study Complete
Location
GSK Investigational Site
Kanwal, New South Wales, Australia, 2259
Status
Study Complete
Location
GSK Investigational Site
Karlsruhe, Baden-Wuerttemberg, Germany, 76137
Status
Study Complete
Location
GSK Investigational Site
Koblenz, Rheinland-Pfalz, Germany, 56068
Status
Study Complete
Location
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 51069
Status
Study Complete
Location
GSK Investigational Site
Lancaster, South Carolina, United States, 29720
Status
Study Complete
Location
GSK Investigational Site
Lincoln, California, United States, 95648
Status
Study Complete
Location
GSK Investigational Site
Luebeck, Schleswig-Holstein, Germany, 23552
Status
Study Complete
Location
GSK Investigational Site
Mar del Plata, Buenos Aires, Argentina, 7600
Status
Study Complete
Location
GSK Investigational Site
Mar del Plata, Buenos Aires, Argentina, B7600FZN
Status
Study Complete
Location
GSK Investigational Site
Marbella - Málaga, Andalucia, Spain, 29603
Status
Study Complete
Location
GSK Investigational Site
Middelburg, Mpumalanga, South Africa, 1050
Status
Study Complete
Location
GSK Investigational Site
Minneapolis, Minnesota, United States, 55407
Status
Study Complete
Location
GSK Investigational Site
Moncton, New Brunswick, Canada, E1G1A7
Status
Study Complete
Location
GSK Investigational Site
Monroe, North Carolina, United States, 28112
Status
Study Complete
Location
GSK Investigational Site
Mooresville, North Carolina, United States, 28117
Status
Study Complete
Location
GSK Investigational Site
Morgantown, West Virginia, United States, 26505
Status
Study Complete
Location
GSK Investigational Site
Mt. Pleasant, South Carolina, United States, 29464
Status
Study Complete
Location
GSK Investigational Site
Natchitoches, Louisiana, United States, 71457
Status
Study Complete
Location
GSK Investigational Site
O'Fallon, Illinois, United States, 62269
Status
Study Complete
Location
GSK Investigational Site
Orlando, Florida, United States, 32825
Status
Study Complete
Location
GSK Investigational Site
Osnabrueck, Niedersachsen, Germany, 49074
Status
Study Complete
Location
GSK Investigational Site
Paraná, Buenos Aires, Argentina, E3100BHK
Status
Study Complete
Location
GSK Investigational Site
Phoenix, Arizona, United States, 85018
Status
Study Complete
Location
GSK Investigational Site
Pordenone, Friuli-Venezia-Giulia, Italy, 33170
Status
Study Complete
Location
GSK Investigational Site
Port Macquarie, New South Wales, Australia, 2444
Status
Study Complete
Location
GSK Investigational Site
Quilmes, Buenos Aires, Argentina, B1878FNR
Status
Study Complete
Location
GSK Investigational Site
Reggio Emilia, Emilia-Romagna, Italy, 42100
Status
Study Complete
Location
GSK Investigational Site
Rheine, Nordrhein-Westfalen, Germany, 48431
Status
Study Complete
Location
GSK Investigational Site
Riccione (RN), Emilia-Romagna, Italy, 47838
Status
Study Complete
Location
GSK Investigational Site
Rock Hill, South Carolina, United States, 29732
Status
Study Complete
Location
GSK Investigational Site
Rosario, Santa Fe, Argentina, S2002OJN
Status
Study Complete
Location
GSK Investigational Site
Ruedersdorf, Brandenburg, Germany, 15562
Status
Study Complete
Location
GSK Investigational Site
San Felice a Cancello (CE), Campania, Italy, 81027
Status
Study Complete
Location
GSK Investigational Site
San Miguel de Tucumán, Argentina, 4000
Status
Study Complete
Location
GSK Investigational Site
Schleswig, Schleswig-Holstein, Germany, 24837
Status
Study Complete
Location
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, Germany, 19055
Status
Study Complete
Location
GSK Investigational Site
Seneca, South Carolina, United States, 29678
Status
Study Complete
Location
GSK Investigational Site
Spartanburg, South Carolina, United States, 29303
Status
Study Complete
Location
GSK Investigational Site
St. Charles, Missouri, United States, 63301
Status
Study Complete
Location
GSK Investigational Site
St. Charles-Borromee, Québec, Canada, J6E 2B4
Status
Study Complete
Location
GSK Investigational Site
St. Louis, Missouri, United States, 63141
Status
Study Complete
Location
GSK Investigational Site
Sydney, New South Wales, Australia, 2010
Status
Study Complete
Location
GSK Investigational Site
Teuchern, Sachsen-Anhalt, Germany, 06682
Status
Study Complete
Location
GSK Investigational Site
Union, South Carolina, United States, 29379
Status
Study Complete
Location
GSK Investigational Site
Vicente Lopez, Buenos Aires, Argentina, B1602DOH
Status
Study Complete
Location
GSK Investigational Site
Wardenburg, Niedersachsen, Germany, 26203
Status
Study Complete
Location
GSK Investigational Site
Warendorf, Nordrhein-Westfalen, Germany, 48231
Status
Study Complete
Location
GSK Investigational Site
Wiesloch, Baden-Wuerttemberg, Germany, 69168
Status
Study Complete
Location
GSK Investigational Site
Winston Salem, North Carolina, United States, 27103
Status
Study Complete
Location
GSK Investigational Site
Woodbury, Minnesota, United States, 55125
Status
Study Complete
Study documents
Statistical analysis plan
Available language(s): English
Protocol
Available language(s): English
Clinical study report
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2018-18-06
Actual study completion date
2018-18-06
Plain language summaries
Summary of results in plain language
Available language(s): Dutch, Afrikaans, French (Canadian), German, Spanish, Spanish (Argentina), Spanish (Mexico), French, Italian, Swedish, English
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
Participate in clinical trial
Access to clinical trial data by researchers
Visit website