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)

NCT ID: NCT01822899

Last Updated: 2017-09-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 717 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-04
• Study Completion Date: 2013-10-07

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

Study Design

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

Study Groups

Umeclidinium bromide/Vilanterol + placebo ACCUHALER/DISKUS

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.

Group Type: EXPERIMENTAL

Umeclidinium bromide/Vilanterol

Intervention Type: 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).

Placebo ACCUHALER/DISKUS

Intervention Type: 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).

Fluticasone propionate/Salmeterol + placebo NDPI

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.

Group Type: ACTIVE_COMPARATOR

Fluticasone propionate/Salmeterol

Intervention Type: 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).

Placebo NDPI

Intervention Type: DRUG

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

Interventions

Umeclidinium bromide/Vilanterol

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).

Intervention Type: DRUG

Placebo ACCUHALER/DISKUS

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).

Intervention Type: DRUG

Fluticasone propionate/Salmeterol

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).

Intervention Type: DRUG

Placebo NDPI

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study
• Asthma: A current diagnosis of asthma
• Other Respiratory Disorders: Known alpha-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: 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 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)
• 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

Benešov, , Czechia

GSK Investigational Site

Cvikov, , Czechia

GSK Investigational Site

Kralupy nad Vltavou, , Czechia

GSK Investigational Site

Kroměříž, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Rokycany, , Czechia

GSK Investigational Site

Teplice, , Czechia

GSK Investigational Site

Třebíč, , Czechia

GSK Investigational Site

Copenhagen, , Denmark

GSK Investigational Site

Hvidovre, , Denmark

GSK Investigational Site

Odense C, , Denmark

GSK Investigational Site

Roskilde, , Denmark

GSK Investigational Site

Dillingen an der Donau, Bavaria, Germany

GSK Investigational Site

Rüdersdorf, Brandenburg, Germany

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Neu-Isenburg, Hesse, Germany

GSK Investigational Site

Schwerin, Mecklenburg-Vorpommern, Germany

GSK Investigational Site

Delitzsch, Saxony, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Magdeburg, Saxony-Anhalt, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Balassagyarmat, , Hungary

GSK Investigational Site

Budaörs, , Hungary

GSK Investigational Site

Debrecen, , Hungary

GSK Investigational Site

Debrecen, , Hungary

GSK Investigational Site

Farkasgyepű, , Hungary

GSK Investigational Site

Gödöllő, , Hungary

GSK Investigational Site

Miskolc, , Hungary

GSK Investigational Site

Mosonmagyaróvár, , Hungary

GSK Investigational Site

Nyíregyháza, , Hungary

GSK Investigational Site

Pécs, , Hungary

GSK Investigational Site

Szeged, , Hungary

GSK Investigational Site

Székesfehérvár, , Hungary

GSK Investigational Site

Szikszó, , Hungary

GSK Investigational Site

Dordrecht, , Netherlands

GSK Investigational Site

Eindhoven, , Netherlands

GSK Investigational Site

Heerlen, , Netherlands

GSK Investigational Site

Hoorn, , Netherlands

GSK Investigational Site

Kloosterhaar, , Netherlands

GSK Investigational Site

Sneek, , Netherlands

GSK Investigational Site

Gdansk, , Poland

GSK Investigational Site

Inowrocław, , Poland

GSK Investigational Site

Krakow, , Poland

GSK Investigational Site

Poznan, , Poland

GSK Investigational Site

Skierniewice, , Poland

GSK Investigational Site

Słupsk, , Poland

GSK Investigational Site

Barnaul, , Russia

GSK Investigational Site

Blagoveshchensk, , Russia

GSK Investigational Site

Kaluga, , Russia

GSK Investigational Site

Kazan', , Russia

GSK Investigational Site

Khantymansiysk, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Nizhny Novgorod, , Russia

GSK Investigational Site

Orenburg, , Russia

GSK Investigational Site

Petrozavodsk, , Russia

GSK Investigational Site

Ryazan, , Russia

GSK Investigational Site

Saint Pertersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saratov, , Russia

GSK Investigational Site

Tomsk, , Russia

GSK Investigational Site

Ufa, , Russia

GSK Investigational Site

Barcelona, Catalonia, Spain

GSK Investigational Site

Alicante, , Spain

GSK Investigational Site

L'Hospitalet de Llobregat, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Pama de Mallorca, , Spain

GSK Investigational Site

Ponferrada (León), , Spain

GSK Investigational Site

Valladolid, , Spain

Countries

Czechia; Denmark; Germany; Hungary; Netherlands; Poland; Russia; Spain

References

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.

Reference Type: DERIVED

PMID: 26286141 (View on PubMed)

Study Documents

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

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Other Identifiers

116134

Identifier Type: -

Identifier Source: org_study_id