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

NCT ID: NCT01817764

Last Updated: 2017-11-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 707 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-01
• Study Completion Date: 2013-10-25

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Umeclidinium/vilanterol Arm

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

Group Type: EXPERIMENTAL

Umeclidinium/vilanterol

Intervention Type: 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

Placebo

Intervention Type: 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

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

Group Type: ACTIVE_COMPARATOR

Fluticasone propionate/salmeterol

Intervention Type: 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

Placebo

Intervention Type: 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)

Interventions

Umeclidinium/vilanterol

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

Intervention Type: DRUG

Fluticasone propionate/salmeterol

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

Intervention Type: DRUG

Placebo

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)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• Women who are pregnant or lactating or are planning on becoming pregnant during the study
• A current diagnosis of asthma
• Other Respiratory Disorders: Known α-1 antitrypsin deficiency, active lung infections (such as tuberculosis), and lung cancer are absolute exclusionary conditions. A subject, who, in the opinion of the investigator, has any other significant respiratory condition in addition to COPD should be excluded. Examples may include clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or interstitial lung disease. Inactive tuberculosis in more than one lobe is exclusionary. Allergic rhinitis is not exclusionary
• Other Diseases/Abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled and/or a previous history of cancer in remission for <5 years prior to Visit 1 (localized carcinoma of the skin that has been resected for cure is not exclusionary). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study
• 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)
• 12-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)
• 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 exclusionary
• 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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Jasper, Alabama, United States

GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

San Diego, California, United States

GSK Investigational Site

Clearwater, Florida, United States

GSK Investigational Site

Columbus, Ohio, United States

GSK Investigational Site

Gaffney, South Carolina, United States

GSK Investigational Site

Greenville, South Carolina, United States

GSK Investigational Site

Rock Hill, South Carolina, United States

GSK Investigational Site

Spartanburg, South Carolina, United States

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Mar del Plata, Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Mendoza, , Argentina

GSK Investigational Site

Mendoza, , Argentina

GSK Investigational Site

San Miguel de Tucumán, , Argentina

GSK Investigational Site

Quillota, Región de Valparaíso, Chile

GSK Investigational Site

Valparaíso, Región de Valparaíso, Chile

GSK Investigational Site

Santiago, Región Metro de Santiago, Chile

GSK Investigational Site

Santiago, Región Metro de Santiago, Chile

GSK Investigational Site

Santiago, Región Metro de Santiago, Chile

GSK Investigational Site

Santiago, , Chile

GSK Investigational Site

Santiago, , Chile

GSK Investigational Site

Santiago, , Chile

GSK Investigational Site

Viña del Mar, , Chile

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Haidari / Athens, , Greece

GSK Investigational Site

Heraklion, Crete, , Greece

GSK Investigational Site

Rethymnon, Crete, , Greece

GSK Investigational Site

Thessaloniki, , Greece

GSK Investigational Site

Thessaloniki, , Greece

GSK Investigational Site

Lima, Lima Province, Peru

GSK Investigational Site

Bacau, , Romania

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Cluj-Napoca, , Romania

GSK Investigational Site

Iași, , Romania

GSK Investigational Site

Ploieşti, , Romania

GSK Investigational Site

Ploieşti, , Romania

GSK Investigational Site

Râmnicu Vâlcea, , Romania

GSK Investigational Site

Suceava, , Romania

GSK Investigational Site

Timișoara, , Romania

GSK Investigational Site

Dnipropetrovsk, , Ukraine

GSK Investigational Site

Donetsk, , Ukraine

GSK Investigational Site

Donetsk, , Ukraine

GSK Investigational Site

Kharkiv, , Ukraine

GSK Investigational Site

Kiev, , Ukraine

GSK Investigational Site

Kyiv, , Ukraine

GSK Investigational Site

Kyiv, , Ukraine

GSK Investigational Site

Kyiv, , Ukraine

GSK Investigational Site

Kyiv, , Ukraine

GSK Investigational Site

Kyiv, , Ukraine

GSK Investigational Site

Poltava, , Ukraine

GSK Investigational Site

Vinnytsia, , Ukraine

GSK Investigational Site

Yalta, , Ukraine

Countries

United States; Argentina; Chile; Greece; Peru; Romania; Ukraine

References

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.

Reference Type: DERIVED

PMID: 26006754 (View on PubMed)

Study Documents

Document Type: Study Protocol

View Document

Document Type: Clinical Study Report

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Annotated Case Report Form

View Document

Document Type: Informed Consent Form

View Document

Document Type: Individual Participant Data Set

View Document

Document Type: Dataset Specification

View Document

Related Links

https://www.clinicalstudydatarequest.com

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

Other Identifiers

114930

Identifier Type: -

Identifier Source: org_study_id