A 12-week Study to Evaluate the Efficacy and Safety of Umeclidinium Compared With Tiotropium in Subjects With Chronic Obstructive Pulmonary Disease
A Randomized, Blinded, Double-dummy, Parallel-group Study to Evaluate the Efficacy and Safety of Umeclidinium (UMEC) 62.5 mcg Compared With Tiotropium 18 mcg in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
1 other identifier
interventional
1,017
13 countries
99
Brief Summary
This is a multicentre, randomized, blinded, double dummy, parallel group study to evaluate the efficacy and safety of UMEC inhalation powder\[ (62.5 microgram (mcg) once daily (QD)\] when administered via a novel Dry Powder Inhaler compared with tiotropium (18 mcg QD) administered via a HANDIHALER® inhaler over a treatment period of 12 weeks (24 weeks in Germany) in subjects with chronic obstructive pulmonary disease (COPD). At the end of the run-in period, subjects who meet the randomization criteria will be randomized to receive UMEC 62.5 mcg administered via novel dry powder inhaler(nDPI) + Placebo administered via HANDIHALER inhaler OR Tiotropium 18 mcg administered via HANDIHALER inhaler + Placebo administered via nDPI in a 1:1 ratio. There will be up to 8 clinic visits conducted on an outpatient basis at Pre-Screening (Visit 0), Screening (Visit 1), a 7 to 14 day run-in period, randomization at Day 1 (Visit 2), and after randomization at Day 2 (Visit 3), Day 28 (Visit 4), Day 56 (Visit 5), Day 84 (Visit 6) and Day 85 (Visit 7). For subjects enrolled in Germany, there will be an additional 3 visits at Day 112 (Visit 8), Day 140 (Visit 9) and Day 168 (Visit 10). The total duration of subject participation in the study will be approximately 15 weeks (27 weeks in Germany). The primary endpoint of the study is clinic visit trough forced expiratory volume in one second (FEV1) on treatment Day 85. All subjects will have spirometry performed at clinic Visits 1 though 7. Trough spirometry will be obtained 23 and 24 hours after the previous day's dose of blinded study medication at Visits 3 to 7. HANDIHALER is a registered trademark of Boehringer Ingelheim Pharma GmbH \& Co. KG.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Sep 2014
Shorter than P25 for phase_3
99 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 31, 2014
CompletedFirst Posted
Study publicly available on registry
August 4, 2014
CompletedStudy Start
First participant enrolled
September 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 25, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
June 15, 2015
CompletedResults Posted
Study results publicly available
February 9, 2016
CompletedJanuary 24, 2018
January 1, 2018
9 months
July 31, 2014
January 11, 2016
January 18, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) on Day 85
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 Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 84 (Week 12). Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84 and 85. Baseline trough FEV1 is the mean of the two assessments made -30 and -5 minutes (min) pre-dose on Day 1. Change from baseline was calculated as the trough FEV1 value on Day 85 minus the BL value. Analysis performed using a repeated measures model with covariates of treatment, baseline FEV1, centre group, 24 hour subset flag, Day, Day by baseline and Day by treatment interactions. The least squares mean changes are presented here.
Baseline (BL) and Day 85
Study Arms (2)
Umeclidinium 62.5 mcg + placebo
EXPERIMENTALSubjects will receive UMEC Inhalation Powder 62.5 mcg once daily via nDPI plus placebo once daily via HANDIHALER inhaler for 12 weeks (24 weeks in Germany). Subjects will be instructed to take one inhalation each morning from both the nDPI and the HANDIHALER inhaler
Tiotropium 18mcg + placebo
ACTIVE COMPARATORSubjects will receive Tiotropium 18 mcg once daily via HANDIHALER inhaler plus placebo once daily via nDPI for 12 weeks (24 weeks in Germany). Subjects will be instructed to take one inhalation each morning from both the nDPI and the HANDIHALER inhaler
Interventions
Umeclidinium 62.5 mcg once daily in the morning via nDPI
Umeclidinium matching placebo once daily in the morning via nDPI
Tiotropium 18 mcg once daily in the morning via HANDIHALER inhaler
Tiotropium matching placebo once daily in the morning via HANDIHALER inhaler
Eligibility Criteria
You may qualify if:
- Type of subject: outpatient.
- Informed Consent: A signed and dated written informed consent prior to study participation.
- Age: Subjects 40 years of age or older at Visit 1.
- Gender: Male and female subjects are eligible to participate in the study. A female is eligible to enter and participate in the study if she is of:
- Non-child bearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g., age appropriate, \> 45 years, in the absence of hormone replacement therapy. OR Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the acceptable contraceptive methods used consistently and correctly (i.e., in accordance with the approved product label and the instructions of the physician for the duration of the study - screening to follow-up contact). - Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society
- Smoking History: Current or former cigarette smokers with a history of cigarette smoking of \>=10 pack-years \[number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g. 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years both equal 10 pack-years)\]. 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.
- Severity of Disease: A pre and post-albuterol/salbutamol FEV1/ Forced Vital Capacity (FVC) ratio of \<0.70 and a post-albuterol/salbutamol FEV1 of \>=30% and \<=70% of predicted normal values at Visit 1. Predicted values will be based upon the ERS Global Lung Function Initiative
- Dyspnea: A score of \>=2 on the Modified Medical Research Council Dyspnea Scale (mMRC) at Visit 1.
You may not qualify if:
- Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
- Asthma: A current diagnosis of asthma.
- Other Diseases/Abnormalities: 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 condition (e.g. neurological condition) that is likely to affect respiratory function should not be included in the study.
- Severe Hepatic Impairment: Patients with severe hepatic impairment (Child-Pugh class C) should be excluded unless, in the opinion of the investigator, the benefit is likely to outweigh the risk.
- Moderate to severe Renal Impairment: Patients with moderate to severe renal impairment (e.g., end-stage renal disease requiring dialysis) should be excluded, unless in the opinion of the investigator, the benefit is likely to outweigh the risk.
- Unstable or life threatening cardiac disease: Long-acting muscarinic antagonists (LAMAs) should be used with caution in subjects with severe cardiovascular disease. In the opinion of the investigator, use should 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; Unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months; New York Heart Association Class IV heart failure
- Contraindications: Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, sympathomimetic, lactose/milk protein or magnesium stearate.
- Antimuscarinic effects: Subjects with medical conditions such as narrow-angle glaucoma, urinary retention, prostatic hypertrophy, or bladder neck obstruction should only be included if, in the opinion of the study physician, the benefit outweighs the risk.
- Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
- Lung Resection: Lung volume reduction surgery within the 12 months prior to Visit 1.
- Lead electrocardiogram (ECG): Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility. The Investigator will determine the clinical significance of each abnormal 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; Sustained or nonsustained ventricular tachycardia; Second degree heart block Mobitz type II or third degree heart block (unless pacemaker or defibrillator had been inserted)
- Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
- Medications Prior to Screening: Use of the following medications according to the following defined time intervals prior to Visit 1: Depot corticosteroids-12 weeks; Systemic, oral or parenteral corticosteroids- 6 weeks; Antibiotics (for lower respiratory tract infection)- 6 weeks ; long-acting beta2-agonists/inhaled corticosteroids (LABA/ICS) combination products if LABA/ICS therapy is discontinued completely-30 days; LABA/ICS combination products only If discontinuing ICS/LABA therapy and switching to ICS monotherapy- 48 hours for the salmeterol or formoterol component, 14 days for the vilanterol component \[The dose of ICS must be a dose of fluticasone propionate (FP) or equivalent but not to exceed 1000 mcg/day\] ; Use of ICS at a dose \>1000 mcg/day of FP or equivalent- 30 days; Initiation or discontinuation of ICS use-30 days (Use of ICS is permitted provided the dose does not exceed 1000mcg of FP or equivalent; ICS use not to be initiated or discontinued within 30 days prior to Visit 1, except for subjects on LABA/ICS therapy who may discontinue the ICS/LABA product as indicated in the table above and switch to ICS monotherapy); Phosphodiesterase 4 (PDE4) Inhibitor (roflumilast)- 14 days; Inhaled long acting beta2 agonists (LABAs): salmeterol, formoterol-48 hours, olodaterol, indacaterol, vilanterol- 14 days; LAMAs: tiotropium, aclidinium, glycopyrronium, umeclidinium- 7 days; LAMA/LABA combination products if LAMA/LABA therapy is discontinued completely- Apply whichever mono component has the longest washout; Theophyllines- 48 hours; Oral beta2-agonists: Long-acting- 48 hours, Short-acting 12 hours; Inhaled short acting beta2-agonists- 4 hours (Use of study provided albuterol/salbutamol is permitted during the study, except in the 4-hour period prior to spirometry testing) ; Inhaled short-acting anticholinergics- 4 hours; Inhaled short-acting anticholinergic/short-acting beta2-agonist combination products- 4 hours; Any other investigational medication - 30 days or within 5 drug half lives (whichever is longer).
- Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (e.g. albuterol/salbutamol) via nebulized therapy.
- Pulmonary Rehabilitation Program: Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (99)
GSK Investigational Site
Spartanburg, South Carolina, 29303, United States
GSK Investigational Site
Buenos Aires, C1425BEN, Argentina
GSK Investigational Site
Buenos Aires, C1426ABP, Argentina
GSK Investigational Site
Winnipeg, Manitoba, R2K 3S8, Canada
GSK Investigational Site
St. John's, Newfoundland and Labrador, A1A 3R5, Canada
GSK Investigational Site
Truro, Nova Scotia, B2N 1L2, Canada
GSK Investigational Site
Greater Sudbury, Ontario, P3E 1H5, Canada
GSK Investigational Site
Toronto, Ontario, M3J 2C5, Canada
GSK Investigational Site
Toronto, Ontario, M5G 1N8, Canada
GSK Investigational Site
Montreal, Quebec, H2R 1V6, Canada
GSK Investigational Site
Québec, Quebec, G1V 4G5, Canada
GSK Investigational Site
Québec, Quebec, G1W 4R4, Canada
GSK Investigational Site
Saint-Charles-Borromée, Quebec, J6E 2B4, Canada
GSK Investigational Site
Sherbrooke, Quebec, J1H 5N4, Canada
GSK Investigational Site
Valparaíso, Región de Valparaíso, 2341131, Chile
GSK Investigational Site
Santiago, Región Metro de Santiago, 7500692, Chile
GSK Investigational Site
Santiago, Región Metro de Santiago, 7860406, Chile
GSK Investigational Site
Santiago, Región Metro de Santiago, 8360160, Chile
GSK Investigational Site
Talcahuano, 4270918, Chile
GSK Investigational Site
Aarhus C, 8000, Denmark
GSK Investigational Site
Hvidovre, 2650, Denmark
GSK Investigational Site
København NV, 2400, Denmark
GSK Investigational Site
Odense, DK-5000, Denmark
GSK Investigational Site
Bletterans, 39140, France
GSK Investigational Site
Nantes, 44277, France
GSK Investigational Site
Toulon, 83000, France
GSK Investigational Site
Tours, 37100, France
GSK Investigational Site
Vieux-Condé, 59690, France
GSK Investigational Site
Aschaffenburg, Bavaria, 63739, Germany
GSK Investigational Site
Frankfurt am Main, Hesse, 60389, Germany
GSK Investigational Site
Neu-Isenburg, Hesse, 63263, Germany
GSK Investigational Site
Rodgau, Hesse, 63110, Germany
GSK Investigational Site
Wiesbaden, Hesse, 65187, Germany
GSK Investigational Site
Dresden, Saxony, 01069, Germany
GSK Investigational Site
Teuchern, Saxony-Anhalt, 06682, Germany
GSK Investigational Site
Schmölln, Thuringia, 04626, Germany
GSK Investigational Site
Berlin, 10117, Germany
GSK Investigational Site
Berlin, 10717, Germany
GSK Investigational Site
Berlin, 13156, Germany
GSK Investigational Site
Riccione (RN), Emilia-Romagna, 47838, Italy
GSK Investigational Site
Milan, Lombardy, 20138, Italy
GSK Investigational Site
Torrette (AN), The Marches, 60020, Italy
GSK Investigational Site
Pisa, Tuscany, 56124, Italy
GSK Investigational Site
Negrar, Veneto, 37024, Italy
GSK Investigational Site
Bacau, 600252, Romania
GSK Investigational Site
Brăila, 810003, Romania
GSK Investigational Site
Bucharest, 030303, Romania
GSK Investigational Site
Codlea, 505100, Romania
GSK Investigational Site
Comuna Alexandru Cel Bun, 617507, Romania
GSK Investigational Site
Deva, 330084, Romania
GSK Investigational Site
Focşani, 620043, Romania
GSK Investigational Site
Galati, 800189, Romania
GSK Investigational Site
Ploieşti, 100379, Romania
GSK Investigational Site
Timișoara, 300310, Romania
GSK Investigational Site
Arkhangelsk, 153000, Russia
GSK Investigational Site
Arkhangelsk, 163001, Russia
GSK Investigational Site
Barnaul, 656 045, Russia
GSK Investigational Site
Irkutsk, 664003, Russia
GSK Investigational Site
Izhevsk, 426063, Russia
GSK Investigational Site
Kemerovo, 650002, Russia
GSK Investigational Site
Moscow, 115 280, Russia
GSK Investigational Site
Moscow, 117997, Russia
GSK Investigational Site
Novosibirsk, 630102, Russia
GSK Investigational Site
Saint Petersburg, 194354, Russia
GSK Investigational Site
Saint Petersburg, 194356, Russia
GSK Investigational Site
Saint Petersburg, 196084, Russia
GSK Investigational Site
Saint Petersburg, 198216, Russia
GSK Investigational Site
Saint Petersburg, 198260, Russia
GSK Investigational Site
Saint Petersburg, Russia
GSK Investigational Site
Sestroretsk, 197706, Russia
GSK Investigational Site
Sochi, 354057, Russia
GSK Investigational Site
Stavropol, 355017, Russia
GSK Investigational Site
Tomsk, 634050, Russia
GSK Investigational Site
Ufa, 450071, Russia
GSK Investigational Site
Vladimir, 600023, Russia
GSK Investigational Site
Port Elizabeth, Eastern Cape, 6001, South Africa
GSK Investigational Site
Boksburg, Gauteng, 1459, South Africa
GSK Investigational Site
Bellville, 7530, South Africa
GSK Investigational Site
Durban, 4001, South Africa
GSK Investigational Site
Korsten, 6014, South Africa
GSK Investigational Site
Lynnwood Ridge, Pretoria, 0040, South Africa
GSK Investigational Site
Mowbray, 7700, South Africa
GSK Investigational Site
Somerset West, 7130, South Africa
GSK Investigational Site
Vrededorp, 2129, South Africa
GSK Investigational Site
Welkom, 9460, South Africa
GSK Investigational Site
Bucheon-Si, Gyeonggi-Do, 420-767, South Korea
GSK Investigational Site
Seoul, 130-709, South Korea
GSK Investigational Site
Seoul, 134-814, South Korea
GSK Investigational Site
Seoul, 136-705, South Korea
GSK Investigational Site
Seoul, 156-707, South Korea
GSK Investigational Site
Wonju-si, Gangwon-do, 220-701, South Korea
GSK Investigational Site
Dnipropetrovsk, 49074, Ukraine
GSK Investigational Site
Kharkiv, 61002, Ukraine
GSK Investigational Site
Kharkiv, 61039, Ukraine
GSK Investigational Site
Kiev, 03680, Ukraine
GSK Investigational Site
Kryvyi Rig, 50096, Ukraine
GSK Investigational Site
Kyiv, 03038, Ukraine
GSK Investigational Site
Poltava, 36038, Ukraine
GSK Investigational Site
Zaporizhzhia, 69050, Ukraine
Related Publications (2)
Shah D, Driessen M, Risebrough N, Baker T, Naya I, Briggs A, Ismaila AS. Cost-effectiveness of umeclidinium compared with tiotropium and glycopyrronium as monotherapy for chronic obstructive pulmonary disease: a UK perspective. Cost Eff Resour Alloc. 2018 May 10;16:17. doi: 10.1186/s12962-018-0101-3. eCollection 2018.
PMID: 29773969DERIVEDFeldman G, Maltais F, Khindri S, Vahdati-Bolouri M, Church A, Fahy WA, Trivedi R. A randomized, blinded study to evaluate the efficacy and safety of umeclidinium 62.5 mug compared with tiotropium 18 mug in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2016 Apr 7;11:719-30. doi: 10.2147/COPD.S102494. eCollection 2016.
PMID: 27103795DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- GSK Response Center
- Organization
- GlaxoSmithKline
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 31, 2014
First Posted
August 4, 2014
Study Start
September 1, 2014
Primary Completion
May 25, 2015
Study Completion
June 15, 2015
Last Updated
January 24, 2018
Results First Posted
February 9, 2016
Record last verified: 2018-01
Data Sharing
- IPD Sharing
- Will share
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.