A Study to Compare the Efficacy and Safety of Umeclidinium/Vilanterol and Fluticasone Propionate/Salmeterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

NCT01817764 | Completed Phase 3 Results

• 1 other identifier: 114930
• Study Type: interventional
• Target: 707
• Locations: 7 countries
• Sites: 59

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 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 250/50 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

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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in 24-hour Weighted-mean Serial FEV1 on Treatment 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. Weighted mean is 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. Change from Baseline was calculated as the value at Day 84 minus the value at Baseline. Analysis was performed using an analysis of covariance of treatment, Baseline (mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1), and smoking status. par.=participants.

  Baseline and Day 84

Secondary Outcomes (1)

• Change From Baseline in Trough FEV1 on Day 85

  Baseline and Day 85

Study Arms (2)

Umeclidinium/vilanterol Arm

EXPERIMENTAL

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

Drug: Umeclidinium/vilanterol; Drug: Placebo

Fluticasone propionate/salmeterol Arm

ACTIVE COMPARATOR

The subjects will receive FSC 250/50 mcg, administered as one inhalation each morning and evening via ACCUHALER/DISKUS and placebo administered once-daily in the morning via NDPI

Drug: Fluticasone propionate/salmeterol; Drug: Placebo

Interventions

Umeclidinium/vilanterol DRUG

Dry white powder delivered via NDPI (2 strips with 30 blisters each, first containing UMEC 62.5 mcg per blister and second containing VI 25 mcg per blister), administered as one inhalation of UMEC/VI 62.5/25 mcg once-daily in the morning

Umeclidinium/vilanterol Arm

Fluticasone propionate/salmeterol DRUG

Dry white powder delivered via ACCUHALER/DISKUS (1 strip with 60 blisters, containing 250 mcg fluticasone propionate and 50 mcg salmeterol per blister), administered as one inhalation of FSC 250/50 mcg each morning and evening

Fluticasone propionate/salmeterol Arm

Placebo DRUG

Placebo will be administered via ACCUHALER/DISKUS or NDPI. Dry white powder administered as one inhalation each morning and evening via ACCUHALER/DISKUS (1 strip with 60 blisters containing placebo) OR once-daily in the morning via NDPI (2 strips with 30 blisters each, containing placebo)

Fluticasone propionate/salmeterol Arm; Umeclidinium/vilanterol Arm

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
• A signed and dated written informed consent prior to study participation
• Male or female subjects, 40 years of age or older at Visit 1
• 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). - A female is eligible to enter and participate in the study if she is of: Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the following acceptable contraceptive methods as listed in the protocol used consistently and correctly.
• An 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 use cannot be used to calculate pack year history
• Severity of disease: A pre and post-salbutamol FEV1/Forced Vital Capacity (FVC) ratio of \<0.70 and a post-salbutamol FEV1 of \>=30% and \<=70% of predicted normal values calculated using National Health and Nutrition Examination Survey (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:

• Women who are pregnant or lactating or are planning on becoming pregnant during the study
• 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 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 Electrocardiogram (ECG): An abnormal and significant 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 (59)

GSK Investigational Site

Jasper, Alabama, 35501, United States

Location

GSK Investigational Site

Phoenix, Arizona, 85006, United States

Location

GSK Investigational Site

San Diego, California, 92103, United States

Location

GSK Investigational Site

Clearwater, Florida, 33765-2616, United States

Location

GSK Investigational Site

Columbus, Ohio, 43215, United States

Location

GSK Investigational Site

Gaffney, South Carolina, 29340, United States

Location

GSK Investigational Site

Greenville, South Carolina, 29615, United States

Location

GSK Investigational Site

Rock Hill, South Carolina, 29732, United States

Location

GSK Investigational Site

Spartanburg, South Carolina, 29303, United States

Location

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1425AGC, Argentina

Location

GSK Investigational Site

Mar del Plata, Buenos Aires, 7600, Argentina

Location

GSK Investigational Site

Buenos Aires, C1424BSF, Argentina

Location

GSK Investigational Site

Buenos Aires, C1425BEN, Argentina

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GSK Investigational Site

Buenos Aires, C1425FVH, Argentina

Location

GSK Investigational Site

Buenos Aires, C1426ABP, Argentina

Location

GSK Investigational Site

Mendoza, 5500, Argentina

Location

GSK Investigational Site

Mendoza, M5500CCG, Argentina

Location

GSK Investigational Site

San Miguel de Tucumán, 4000, Argentina

Location

GSK Investigational Site

Quillota, Región de Valparaíso, 2260000, Chile

Location

GSK Investigational Site

Valparaíso, Región de Valparaíso, 2341131, Chile

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, 7500800, Chile

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, 8910131, Chile

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, Chile

Location

GSK Investigational Site

Santiago, 8380453, Chile

Location

GSK Investigational Site

Santiago, 8910131, Chile

Location

GSK Investigational Site

Santiago, Chile

Location

GSK Investigational Site

Viña del Mar, 2570017, Chile

Location

GSK Investigational Site

Athens, 106 76, Greece

Location

GSK Investigational Site

Athens, 115 27, Greece

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GSK Investigational Site

Athens, 151 26, Greece

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GSK Investigational Site

Haidari / Athens, 124 62, Greece

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GSK Investigational Site

Heraklion, Crete, 71110, Greece

Location

GSK Investigational Site

Rethymnon, Crete, 74100, Greece

Location

GSK Investigational Site

Thessaloniki, 56429, Greece

Location

GSK Investigational Site

Thessaloniki, 57010, Greece

Location

GSK Investigational Site

Lima, Lima Province, Lima 27, Peru

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GSK Investigational Site

Bacau, 600252, Romania

Location

GSK Investigational Site

Bucharest, 020125, Romania

Location

GSK Investigational Site

Bucharest, 050159, Romania

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GSK Investigational Site

Cluj-Napoca, 400371, Romania

Location

GSK Investigational Site

Iași, 700115, Romania

Location

GSK Investigational Site

Ploieşti, 100184, Romania

Location

GSK Investigational Site

Ploieşti, 100379, Romania

Location

GSK Investigational Site

Râmnicu Vâlcea, 240564, Romania

Location

GSK Investigational Site

Suceava, 720284, Romania

Location

GSK Investigational Site

Timișoara, 300310, Romania

Location

GSK Investigational Site

Dnipropetrovsk, 49051, Ukraine

Location

GSK Investigational Site

Donetsk, 83003, Ukraine

Location

GSK Investigational Site

Donetsk, 83114, Ukraine

Location

GSK Investigational Site

Kharkiv, 61124, Ukraine

Location

GSK Investigational Site

Kiev, 03680, Ukraine

Location

GSK Investigational Site

Kyiv, 01114, Ukraine

Location

GSK Investigational Site

Kyiv, 02091, Ukraine

Location

GSK Investigational Site

Kyiv, 03049, Ukraine

Location

GSK Investigational Site

Kyiv, 03680, Ukraine

Location

GSK Investigational Site

Kyiv, 04201, Ukraine

Location

GSK Investigational Site

Poltava, 36024, Ukraine

Location

GSK Investigational Site

Vinnytsia, 21018, Ukraine

Location

GSK Investigational Site

Yalta, 98603, Ukraine

Location

Related Publications (1)

• Donohue JF, Worsley S, Zhu CQ, Hardaker L, Church A. Improvements in lung function with umeclidinium/vilanterol versus fluticasone propionate/salmeterol in patients with moderate-to-severe COPD and infrequent exacerbations. Respir Med. 2015 Jul;109(7):870-81. doi: 10.1016/j.rmed.2015.04.018. Epub 2015 May 8.

  PMID: 26006754 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

GSK573719; 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 21, 2013
• First Posted: March 25, 2013
• Study Start: March 1, 2013
• Primary Completion: October 1, 2013
• Study Completion: October 25, 2013
• Last Updated: November 8, 2017
• Results First Posted: May 29, 2014

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

AR (9); US (9); GR (8); CL (9); PE (1); RO (10); UA (13)