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

NCT01879410 | Completed Phase 3 Results

• 1 other identifier: 114951
• Study Type: interventional
• Target: 700
• Locations: 7 countries
• Sites: 72

Brief Summary

Umeclidinium/vilanterol (UMEC/VI) is a combination product under development that is used for the treatment of airflow obstruction in patients with COPD. Fluticasone propionate/salmeterol (FSC) is an approved drug that is already in use for the treatment of COPD. This is a multicenter, randomized, double-blind, double-dummy, parallel group study to evaluate the efficacy and safety of UMEC/VI 62.5/25 microgram \[mcg\] once daily administered via Novel Dry Powder Inhaler (NDPI) compared with fluticasone propionate /salmeterol (FSC) 250/50 mcg twice-daily when administered via ACCUHALER/DISKUS inhaler over a treatment period of 12 weeks in subjects with COPD. Eligible subjects will be equally randomized to UMEC/VI 62.5/25 mcg or FSC 250/50 mcg for 12 weeks. A safety follow-up assessment will be conducted approximately 7 days after the end of the study treatment.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline (BL) in 0 to 24 Hour Weighted Mean Forced Expiratory Volume Over 1 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 hours (pre-evening dose), 13, 15, 18, 23, and 24 hours after the morning dose. Baseline is defined as the mean of the assessments made 30 and 5 minutes (min) pre-dose on treatment Day 1. Analysis was performed using an analysis of covariance model with covariates of baseline FEV1 (mean of the two assessments made 30 mins and 5 mins pre-dose on Day 1), smoking status, and treatment. Change from baseline was calculated as the value at Day 84 minus the value at Baseline.

  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)

UMEC/ VI via NDPI + placebo ACCUHALER/DISKUS arm

EXPERIMENTAL

Subjects will receive one inhalation of UMEC/VI 62.5/25 mcg once-daily in the morning via the NDPI and one inhalation of placebo in the morning and evening via ACCUHALER/DISKUS inhaler

Drug: UMEC/VI Inhalation Powder 62.5/25 mcg via NDPI; Drug: Placebo DISKUS

FSC via ACCUHALER/DISKUS + placebo NDPI arm

ACTIVE COMPARATOR

Subjects will receive one inhalation of FSC 250/50 mcg in the morning and evening via ACCUHALER/DISKUS inhaler and one inhalation of placebo administered once-daily in the morning via NDPI

Drug: FSC Inhalation Powder 250/50 mcg via ACCUHALER/DISKUS; Drug: Placebo NDPI

Interventions

UMEC/VI Inhalation Powder 62.5/25 mcg via NDPI DRUG

The drug is administered via NDPI as one inhalation once daily in the morning. NDPI has two strips, each containing 30 blisters of medication. The first strip has UMEC blended with lactose and magnesium stearate in the form of dry white powder with a dosage of 62.5 mcg per blister and the second strip has VI blended with lactose and magnesium stearate in the form of dry white powder with a dosage of 25 mcg per blister.

UMEC/ VI via NDPI + placebo ACCUHALER/DISKUS arm

FSC Inhalation Powder 250/50 mcg via ACCUHALER/DISKUS DRUG

The drug is administered via ACCUHALER/DISKUS inhaler as one inhalation each morning and evening. The inhaler contains a single strip with 60 blisters of medication. The strip has 250 mcg of fluticasone propionate and 50 mcg of salmeterol per blister in the form of dry white powder.

FSC via ACCUHALER/DISKUS + placebo NDPI arm

Placebo DISKUS DRUG

Placebo is administered via ACCUHALER/DISKUS inhaler as one inhalation each morning and evening. The inhaler contains 1 strip with 60 blisters of placebo in the form of dry white powder.

UMEC/ VI via NDPI + placebo ACCUHALER/DISKUS arm

Placebo NDPI DRUG

Placebo is administered via NDPI as one inhalation once daily in the morning. The inhaler contains 2 strips with 30 blisters of placebo per strip in the form of dry white powder.

FSC via ACCUHALER/DISKUS + placebo NDPI 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
• 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 if of child bearing potential, has a negative pregnancy test at screening, and agrees to one of the acceptable contraceptive methods mentioned in the protocol used consistently and correctly:
• Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society as follows: COPD 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/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:

• 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 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, Olodaterol and Indacaterol - 10days, 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).
• Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day. As-needed oxygen use (i.e., \<=12 hours per day) is not ex-clusionary.
• 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 (72)

GSK Investigational Site

Tucson, Arizona, 85723, United States

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GSK Investigational Site

Newport Beach, California, 92663, United States

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GSK Investigational Site

Riverside, California, 92506, United States

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GSK Investigational Site

DeLand, Florida, 32720, United States

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GSK Investigational Site

Coeur d'Alene, Idaho, 83814, United States

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GSK Investigational Site

St Louis, Missouri, 63141, United States

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GSK Investigational Site

Charlotte, North Carolina, 28207, United States

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GSK Investigational Site

Medford, Oregon, 97504, United States

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GSK Investigational Site

Charleston, South Carolina, 29406-7108, United States

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GSK Investigational Site

Easley, South Carolina, 29640, United States

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GSK Investigational Site

Greenville, South Carolina, 29615, United States

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GSK Investigational Site

Seneca, South Carolina, 29678, United States

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GSK Investigational Site

Union, South Carolina, 29379, United States

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GSK Investigational Site

Newport News, Virginia, 23606, United States

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GSK Investigational Site

Renton, Washington, 98055, United States

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GSK Investigational Site

Temuco, Región de La Araucania, Chile

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GSK Investigational Site

Concepción, Región Del Biobio, 4070038, Chile

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GSK Investigational Site

Puente Alto - Santiago, Región Metro de Santiago, 8207257, Chile

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GSK Investigational Site

Santiago, Región Metro de Santiago, 7500551, Chile

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GSK Investigational Site

Santiago, Región Metro de Santiago, 7500710, Chile

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GSK Investigational Site

Santiago, Región Metro de Santiago, 8880465, Chile

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GSK Investigational Site

Talca, Región Metro de Santiago, 3460001, Chile

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GSK Investigational Site

Talcahuano, 4270918, Chile

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GSK Investigational Site

Guadalajara, Jalisco, 44100, Mexico

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GSK Investigational Site

Monterrey, Nuevo León, 64000, Mexico

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GSK Investigational Site

Monterrey, Nuevo León, 64020, Mexico

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GSK Investigational Site

México DF, 14050, Mexico

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GSK Investigational Site

Oaxaca City, 68000, Mexico

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GSK Investigational Site

Bergen, N-5021, Norway

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GSK Investigational Site

Bodø, 8005, Norway

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GSK Investigational Site

Hamar, 2317, Norway

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GSK Investigational Site

Kløfta, 2040, Norway

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GSK Investigational Site

Stavanger, 4005, Norway

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GSK Investigational Site

Trondheim, 7030, Norway

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GSK Investigational Site

Brăila, 810003, Romania

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GSK Investigational Site

Bucharest, 010457, Romania

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GSK Investigational Site

Bucharest, 030317, Romania

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GSK Investigational Site

Cluj-Napoca, 400371, Romania

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GSK Investigational Site

Comuna Alexandru Cel Bun, 617507, Romania

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GSK Investigational Site

Constanța, 900002, Romania

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GSK Investigational Site

Craiova, 200515, Romania

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GSK Investigational Site

Focşani, 620043, Romania

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GSK Investigational Site

Arkhangelsk, 153000, Russia

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GSK Investigational Site

Barnaul, 656 045, Russia

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GSK Investigational Site

Chelyabinsk, 454091, Russia

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GSK Investigational Site

Chita, 672000, Russia

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GSK Investigational Site

Ivanovo, 153005, Russia

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GSK Investigational Site

Izhevsk, 426063, Russia

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GSK Investigational Site

Moscow, 105229, Russia

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GSK Investigational Site

Omsk, 644112, Russia

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GSK Investigational Site

Saint Petersburg, 194356, Russia

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GSK Investigational Site

Saint Petersburg, 198216, Russia

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GSK Investigational Site

Saratov, 410053, Russia

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GSK Investigational Site

Smolensk, 214 019, Russia

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GSK Investigational Site

Tomsk, 634 050, Russia

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GSK Investigational Site

Ulyanovsk, 432063, Russia

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GSK Investigational Site

Vladimir, 600023, Russia

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GSK Investigational Site

Vladivostok, 690950, Russia

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GSK Investigational Site

Voronezh, 394066, Russia

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GSK Investigational Site

Yaroslavl, 150002, Russia

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GSK Investigational Site

Yaroslavl, 150003, Russia

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GSK Investigational Site

Yaroslavl, 150010, Russia

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GSK Investigational Site

Yekaterinburg, 620039, Russia

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GSK Investigational Site

Yekaterinburg, 620109, Russia

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GSK Investigational Site

Meyerspark, Gauteng, 0184, South Africa

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GSK Investigational Site

Bloemfontein, 9301, South Africa

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GSK Investigational Site

Die Wilgers, 0041, South Africa

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GSK Investigational Site

Durban, 4001, South Africa

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GSK Investigational Site

Gatesville, 7764, South Africa

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GSK Investigational Site

Mowbray, 7700, South Africa

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GSK Investigational Site

Reiger Park, 1459, South Africa

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GSK Investigational Site

Somerset West, 7130, South Africa

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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

Condition Hierarchy (Ancestors)

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

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: June 13, 2013
• First Posted: June 17, 2013
• Study Start: June 13, 2013
• Primary Completion: January 1, 2014
• Study Completion: January 9, 2014
• Last Updated: November 8, 2017
• Results First Posted: August 15, 2014

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

RU (22); RO (8); ZA (8); ME (5); NO (6); US (15); CL (8)