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

NCT ID: NCT01879410

Last Updated: 2017-11-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 700 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-13
• Study Completion Date: 2014-01-09

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)

Study Design

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

Study Groups

UMEC/ VI via NDPI + placebo ACCUHALER/DISKUS arm

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

Group Type: EXPERIMENTAL

UMEC/VI Inhalation Powder 62.5/25 mcg via NDPI

Intervention Type: 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.

Placebo DISKUS

Intervention Type: 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.

FSC via ACCUHALER/DISKUS + placebo NDPI arm

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

Group Type: ACTIVE_COMPARATOR

FSC Inhalation Powder 250/50 mcg via ACCUHALER/DISKUS

Intervention Type: 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.

Placebo NDPI

Intervention Type: 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.

Interventions

UMEC/VI Inhalation Powder 62.5/25 mcg via NDPI

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.

Intervention Type: DRUG

FSC Inhalation Powder 250/50 mcg via ACCUHALER/DISKUS

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.

Intervention Type: DRUG

Placebo DISKUS

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.

Intervention Type: DRUG

Placebo NDPI

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.

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 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.

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 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.

• 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

Tucson, Arizona, United States

GSK Investigational Site

Newport Beach, California, United States

GSK Investigational Site

Riverside, California, United States

GSK Investigational Site

DeLand, Florida, United States

GSK Investigational Site

Coeur d'Alene, Idaho, United States

GSK Investigational Site

St Louis, Missouri, United States

GSK Investigational Site

Charlotte, North Carolina, United States

GSK Investigational Site

Medford, Oregon, United States

GSK Investigational Site

Charleston, South Carolina, United States

GSK Investigational Site

Easley, South Carolina, United States

GSK Investigational Site

Greenville, South Carolina, United States

GSK Investigational Site

Seneca, South Carolina, United States

GSK Investigational Site

Union, South Carolina, United States

GSK Investigational Site

Newport News, Virginia, United States

GSK Investigational Site

Renton, Washington, United States

GSK Investigational Site

Temuco, Región de La Araucania, Chile

GSK Investigational Site

Concepción, Región Del Biobio, Chile

GSK Investigational Site

Puente Alto - 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, Región Metro de Santiago, Chile

GSK Investigational Site

Talca, Región Metro de Santiago, Chile

GSK Investigational Site

Talcahuano, , Chile

GSK Investigational Site

Guadalajara, Jalisco, Mexico

GSK Investigational Site

Monterrey, Nuevo León, Mexico

GSK Investigational Site

Monterrey, Nuevo León, Mexico

GSK Investigational Site

México DF, , Mexico

GSK Investigational Site

Oaxaca City, , Mexico

GSK Investigational Site

Bergen, , Norway

GSK Investigational Site

Bodø, , Norway

GSK Investigational Site

Hamar, , Norway

GSK Investigational Site

Kløfta, , Norway

GSK Investigational Site

Stavanger, , Norway

GSK Investigational Site

Trondheim, , Norway

GSK Investigational Site

Brăila, , Romania

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Cluj-Napoca, , Romania

GSK Investigational Site

Comuna Alexandru Cel Bun, , Romania

GSK Investigational Site

Constanța, , Romania

GSK Investigational Site

Craiova, , Romania

GSK Investigational Site

Focşani, , Romania

GSK Investigational Site

Arkhangelsk, , Russia

GSK Investigational Site

Barnaul, , Russia

GSK Investigational Site

Chelyabinsk, , Russia

GSK Investigational Site

Chita, , Russia

GSK Investigational Site

Ivanovo, , Russia

GSK Investigational Site

Izhevsk, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Omsk, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saratov, , Russia

GSK Investigational Site

Smolensk, , Russia

GSK Investigational Site

Tomsk, , Russia

GSK Investigational Site

Ulyanovsk, , Russia

GSK Investigational Site

Vladimir, , Russia

GSK Investigational Site

Vladivostok, , Russia

GSK Investigational Site

Voronezh, , Russia

GSK Investigational Site

Yaroslavl, , Russia

GSK Investigational Site

Yaroslavl, , Russia

GSK Investigational Site

Yaroslavl, , Russia

GSK Investigational Site

Yekaterinburg, , Russia

GSK Investigational Site

Yekaterinburg, , Russia

GSK Investigational Site

Meyerspark, Gauteng, South Africa

GSK Investigational Site

Bloemfontein, , South Africa

GSK Investigational Site

Die Wilgers, , South Africa

GSK Investigational Site

Durban, , South Africa

GSK Investigational Site

Gatesville, , South Africa

GSK Investigational Site

Mowbray, , South Africa

GSK Investigational Site

Reiger Park, , South Africa

GSK Investigational Site

Somerset West, , South Africa

Countries

United States; Chile; Mexico; Norway; Romania; Russia; South Africa

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: Individual Participant Data Set

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Clinical Study Report

View Document

Document Type: Study Protocol

View Document

Document Type: Dataset Specification

View Document

Document Type: Informed Consent Form

View Document

Document Type: Annotated Case Report Form

View Document

Related Links

https://www.clinicalstudydatarequest.com

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Other Identifiers

114951

Identifier Type: -

Identifier Source: org_study_id