A Study to Evaluate the Efficacy and Safety of Umeclidinium Bromide/Vilanterol Compared With Fluticasone Propionate/Salmeterol Over 12 Weeks in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

NCT01822899 | Completed Phase 3 Results

• 1 other identifier: 116134
• Study Type: interventional
• Target: 717
• Locations: 8 countries
• Sites: 78

Brief Summary

This is a multicenter, randomized, double-blind, double-dummy, parallel group study. The purpose of this study is to compare the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) and fluticasone propionate/salmeterol (FSC) in subjects with Chronic Obstructive Pulmonary Disease (COPD). Subjects who meet the eligibility criteria at Screening will complete a 7 to 14 day Run-in period. At the end of the run-in period, approximately 710 eligible subjects will be equally randomized (to complete at least 568 evaluable subjects) to one of the 2 treatment groups for 12 weeks: 1. UMEC/VI 62.5/25 micrograms (mcg) administered as one inhalation once-daily in the morning via the Novel dry powder inhaler (NDPI) + placebo administered as one inhalation each morning and evening via single multidose powdered inhaler (ACCUHALER/DISKUS) or 2. FSC 500/50 mcg administered as one inhalation each morning and evening via ACCUHALER/DISKUS + placebo administered once-daily in the morning via NDPI. A safety Follow-up assessment will be conducted approximately 7 days after the end of the study treatment (Early Withdrawal, if applicable). The total duration of subject participation will be approximately 15 weeks.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Novel Dry Powder Inhaler (NDPI); umeclidinium bromide (UMEC); GSK573719; lung function; GW642444; salmeterol (SAL); fluticasone propionate (FP); vilanterol (VI); Chronic obstructive pulmonary disease

Outcome Measures

Primary Outcomes (1)

• Change From Baseline (BL) in 0 to 24 Hour Weighted Mean Serial Forced Expiratory Volume in One Second (FEV1) at Day 84

  FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The weighted mean was calculated from the pre-dose FEV1 and post-dose FEV1 measurements at 5 and 15 minutes and 1, 3, 6, 9, 12 (pre-evening dose), 13, 15, 18, 23, and 24 hours after the morning dose. Analysis was performed using an analysis of covariance (ANCOVA) model with covariates of treatment, Baseline FEV1 (mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1), and smoking status.

  Baseline and Day 84

Secondary Outcomes (1)

• Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) at Day 85

  Baseline and Day 85

Study Arms (2)

Umeclidinium bromide/Vilanterol + placebo ACCUHALER/DISKUS

EXPERIMENTAL

Subjects will receive UMEC/ VI 62.5/25 mcg, one inhalation administered once-daily in the morning via the NDPI and one placebo ACCUHALER/DISKUS administered as one inhalation each morning and evening.

Drug: Umeclidinium bromide/Vilanterol; Drug: Placebo ACCUHALER/DISKUS

Fluticasone propionate/Salmeterol + placebo NDPI

ACTIVE COMPARATOR

Subjects will receive FSC 500/50 mcg, administered as one inhalation each morning and evening via ACCUHALER/DISKUS + placebo administered once daily in the morning via NDPI.

Drug: Fluticasone propionate/Salmeterol; Drug: Placebo NDPI

Interventions

Umeclidinium bromide/Vilanterol DRUG

Dry white powder of UMEC 62.5 mcg per blister and VI 25 mcg per blister as NDPI with 30 doses (2 strips with 30 blisters per strip).

Umeclidinium bromide/Vilanterol + placebo ACCUHALER/DISKUS

Placebo ACCUHALER/DISKUS DRUG

Dry white powder of matching placebo as multidose dry powder inhaler containing a foil strip with 60 blisters (1 strip with 60 blisters per strip).

Umeclidinium bromide/Vilanterol + placebo ACCUHALER/DISKUS

Fluticasone propionate/Salmeterol DRUG

Dry white powder of fluticasone propionate 500 mcg per blister 50 mcg salmeterol per blister as multidose dry powder inhaler containing a foil strip with 60 blisters (1 strip with 60 blisters per strip).

Fluticasone propionate/Salmeterol + placebo NDPI

Placebo NDPI DRUG

Dry white powder of matching placebo as NDPI with 30 doses (2 strips with 30 blisters per strip).

Fluticasone propionate/Salmeterol + placebo NDPI

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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 or female subjects. 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); or Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the acceptable contraceptive methods listed in the protocol used consistently and correctly
• Diagnosis: established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society as follows: Chronic obstructive pulmonary disease is a preventable and treatable disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences.
• Smoking history: Current or former cigarette smokers with a history of cigarette smoking of \>=10 pack-years \[number of pack years = (number of cigarettes per day/20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)\]. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Pipe and/or cigar smoking cannot be used to calculate pack year history.
• Severity of disease: A pre and post-salbutamol FEV1/FVC ratio of \<0.70 and a post-salbutamol FEV1 of \>=30% and \<=70% of predicted normal values calculated using NHANES III reference equations at Visit 1.
• 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
• Contraindications: A history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, corticosteroid, lactose/milk protein or magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the study physician contraindicates study participation or use of an inhaled anticholinergic.
• Hospitalization: Hospitalization for pneumonia within 12 weeks prior to Visit 1
• History of COPD Exacerbation: A documented history of at least one COPD exacerbation in the 12 months prior to Visit 1 that required either oral corticosteroids, antibiotics, and/or hospitalization. Prior use of antibiotics alone does not qualify as an exacerbation history unless the use was associated with treatment of worsening symptoms of COPD, such as increased dyspnea, sputum volume, or sputum purulence.
• Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1)
• Lead ECG: An abnormal and significant electrocardiogram (ECG) finding from the 12-lead ECG conducted at Visit 1. Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility.
• Medication Prior to Spirometry: Unable to withhold 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, Cytochrome P450 3A4 strong inhibitors - 6 weeks, Herbal medications potentially containing oral or systemic steroids - 6 weeks, Inhaled corticosteroids (ICS) - 30 days, Long-acting beta2-agonist (LABA)/ICS combination products - 30 days, Phosphodiesterase 4 (PDE4) inhibitors (e.g., roflumilast) - 14 days, Inhaled long-acting anticholinergics - 7 days, Theophyllines - 48 hours, Oral leukotriene inhibitors (zafirlukast, montelukast, zileuton) - 48 hours, Oral beta2-agonists Long-acting-48 hours/Short-acting - 12 hours, Inhaled long acting beta2-agonists (LABA, e.g., salmeterol, formoterol, indacaterol) - 48 hours, Inhaled sodium cromoglycate or nedocromil sodium - 24 hours, Inhaled short acting beta2-agonists - 4 hours, 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., 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.
• Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.
• Affiliation with Investigator Site: A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator
• Inability to read: A subject will not be eligible for the study if in the opinion of the investigator the subject cannot read.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (78)

GSK Investigational Site

Benešov, 256 30, Czechia

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GSK Investigational Site

Cvikov, 471 54, Czechia

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GSK Investigational Site

Kralupy nad Vltavou, 278 01, Czechia

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GSK Investigational Site

Kroměříž, 767 55, Czechia

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GSK Investigational Site

Prague, 150 00, Czechia

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GSK Investigational Site

Rokycany, 337 01, Czechia

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GSK Investigational Site

Teplice, 415 10, Czechia

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GSK Investigational Site

Třebíč, 674 01, Czechia

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GSK Investigational Site

Copenhagen, 2400, Denmark

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GSK Investigational Site

Hvidovre, 2650, Denmark

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GSK Investigational Site

Odense C, 5000, Denmark

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GSK Investigational Site

Roskilde, 4000, Denmark

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GSK Investigational Site

Dillingen an der Donau, Bavaria, 89407, Germany

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GSK Investigational Site

Rüdersdorf, Brandenburg, 15562, Germany

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GSK Investigational Site

Frankfurt am Main, Hesse, 60389, Germany

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GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

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GSK Investigational Site

Neu-Isenburg, Hesse, 63263, Germany

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GSK Investigational Site

Schwerin, Mecklenburg-Vorpommern, 19055, Germany

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GSK Investigational Site

Delitzsch, Saxony, 04509, Germany

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GSK Investigational Site

Dresden, Saxony, 01069, Germany

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GSK Investigational Site

Magdeburg, Saxony-Anhalt, 39112, Germany

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GSK Investigational Site

Berlin, 10117, Germany

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GSK Investigational Site

Berlin, 10629, Germany

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GSK Investigational Site

Berlin, 10717, Germany

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GSK Investigational Site

Berlin, 10787, Germany

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GSK Investigational Site

Berlin, 10789, Germany

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GSK Investigational Site

Berlin, 13125, Germany

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GSK Investigational Site

Balassagyarmat, 2660, Hungary

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GSK Investigational Site

Budaörs, 2040, Hungary

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GSK Investigational Site

Debrecen, 4032, Hungary

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GSK Investigational Site

Debrecen, 4043, Hungary

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GSK Investigational Site

Farkasgyepű, 8552, Hungary

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GSK Investigational Site

Gödöllő, 2100, Hungary

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GSK Investigational Site

Miskolc, 3529, Hungary

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GSK Investigational Site

Mosonmagyaróvár, 9200, Hungary

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GSK Investigational Site

Nyíregyháza, 4400, Hungary

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GSK Investigational Site

Pécs, H-7621, Hungary

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GSK Investigational Site

Szeged, 6722, Hungary

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GSK Investigational Site

Székesfehérvár, 8000, Hungary

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GSK Investigational Site

Szikszó, 3800, Hungary

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GSK Investigational Site

Dordrecht, 3318 AT, Netherlands

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GSK Investigational Site

Eindhoven, 5623 EJ, Netherlands

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GSK Investigational Site

Heerlen, 6419 PC, Netherlands

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GSK Investigational Site

Hoorn, 1624 NP, Netherlands

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GSK Investigational Site

Kloosterhaar, 7694 AC, Netherlands

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GSK Investigational Site

Sneek, 8601 ZR, Netherlands

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GSK Investigational Site

Gdansk, 80-169, Poland

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GSK Investigational Site

Inowrocław, 88-100, Poland

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GSK Investigational Site

Krakow, 31-024, Poland

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GSK Investigational Site

Poznan, 60-773, Poland

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GSK Investigational Site

Skierniewice, 96-100, Poland

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GSK Investigational Site

Słupsk, 76-200, Poland

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GSK Investigational Site

Barnaul, 656038, Russia

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GSK Investigational Site

Blagoveshchensk, 675000, Russia

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GSK Investigational Site

Kaluga, 248007, Russia

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GSK Investigational Site

Kazan', 420015, Russia

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GSK Investigational Site

Khantymansiysk, 628012, Russia

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GSK Investigational Site

Moscow, 105 077, Russia

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GSK Investigational Site

Moscow, 115446, Russia

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GSK Investigational Site

Moscow, 121 309, Russia

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GSK Investigational Site

Moscow, 123182, Russia

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GSK Investigational Site

Moscow, 123367, Russia

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GSK Investigational Site

Nizhny Novgorod, 603126, Russia

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GSK Investigational Site

Orenburg, 460018, Russia

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GSK Investigational Site

Petrozavodsk, 185019, Russia

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GSK Investigational Site

Ryazan, 390039, Russia

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GSK Investigational Site

Saint Pertersburg, 196247, Russia

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GSK Investigational Site

Saint Petersburg, 194356, Russia

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GSK Investigational Site

Saratov, 410028, Russia

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GSK Investigational Site

Tomsk, 634 050, Russia

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GSK Investigational Site

Ufa, 450000, Russia

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GSK Investigational Site

Barcelona, Catalonia, 08017, Spain

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GSK Investigational Site

Alicante, 03004, Spain

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GSK Investigational Site

L'Hospitalet de Llobregat, 08907, Spain

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GSK Investigational Site

Madrid, 28041, Spain

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GSK Investigational Site

Pama de Mallorca, 07010, Spain

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GSK Investigational Site

Ponferrada (León), 24411, Spain

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GSK Investigational Site

Valladolid, 47012, Spain

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Related Publications (1)

• Singh D, Worsley S, Zhu CQ, Hardaker L, Church A. Umeclidinium/vilanterol versus fluticasone propionate/salmeterol in COPD: a randomised trial. BMC Pulm Med. 2015 Aug 19;15:91. doi: 10.1186/s12890-015-0092-1.

  PMID: 26286141 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

vilanterol; Fluticasone-Salmeterol Drug Combination

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Salmeterol Xinafoate; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Fluticasone; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2013
• First Posted: April 2, 2013
• Study Start: April 4, 2013
• Primary Completion: October 1, 2013
• Study Completion: October 7, 2013
• Last Updated: September 6, 2017
• Results First Posted: May 29, 2014

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

DE (15); NL (6); HU (13); DK (4); RU (19); PL (6); ES (7); CZ (8)