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

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

DB2114951: A Randomized, Multi-center, Double-blind, Double-dummy, Parallel Group Study to Evaluate the Efficacy Umeclidinium/Vilanterol Compared With Fluticasone Propionate/Salmeterol Over 12 Weeks in Subjects With COPD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01879410
• Other study ID #: 114951
• Status: Completed
• Phase: Phase 3
• First received: June 13, 2013
• Last updated: October 9, 2017
• Start date: June 13, 2013
• Est. completion date: January 9, 2014

Study information

• Verified date: October 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 700
• Est. completion date: January 9, 2014
• Est. primary completion date: January 1, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
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	Temuco	Región De La Araucania
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	México DF
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Oaxaca
Norway	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
Romania	GSK Investigational Site	Braila
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Cluj Napoca
Romania	GSK Investigational Site	Comuna Alexandru cel Bun
Romania	GSK Investigational Site	Constanta
Romania	GSK Investigational Site	Craiova
Romania	GSK Investigational Site	Focsani
Russian Federation	GSK Investigational Site	Arkhangelsk
Russian Federation	GSK Investigational Site	Barnaul
Russian Federation	GSK Investigational Site	Chelyabinsk
Russian Federation	GSK Investigational Site	Chita
Russian Federation	GSK Investigational Site	Ekaterinburg
Russian Federation	GSK Investigational Site	Ekaterinburg
Russian Federation	GSK Investigational Site	Ivanovo
Russian Federation	GSK Investigational Site	Izhevsk
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Omsk
Russian Federation	GSK Investigational Site	Saratov
Russian Federation	GSK Investigational Site	Smolensk
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Ulyanovsk
Russian Federation	GSK Investigational Site	Vladimir
Russian Federation	GSK Investigational Site	Vladivostok
Russian Federation	GSK Investigational Site	Voronezh
Russian Federation	GSK Investigational Site	Yaroslavl
Russian Federation	GSK Investigational Site	Yaroslavl
Russian Federation	GSK Investigational Site	Yaroslavl
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	Meyerspark	Gauteng
South Africa	GSK Investigational Site	Mowbray
South Africa	GSK Investigational Site	Reiger Park
South Africa	GSK Investigational Site	Somerset West
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Coeur d'Alene	Idaho
United States	GSK Investigational Site	DeLand	Florida
United States	GSK Investigational Site	Easley	South Carolina
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Medford	Oregon
United States	GSK Investigational Site	Newport Beach	California
United States	GSK Investigational Site	Newport News	Virginia
United States	GSK Investigational Site	Renton	Washington
United States	GSK Investigational Site	Riverside	California
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	Seneca	South Carolina
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Union	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Chile,  Mexico,  Norway,  Romania,  Russian Federation,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change From Baseline(BL) in Trough Forced Expiratory Volume in One Second (FEV1) at Day 85	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Baseline is defined as the mean of the assessments made 30 and 5 minutes (min) pre-dose on treatment Day 1. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after morning dosing on Day 84. Analysis was performed using a repeated measures model with covariates of treatment, Baseline (mean of the 2 assessments made 30 min and 5 min pre-dose on Day 1), smoking status, day, day by baseline and day by treatment interactions. The model used all available trough FEV1 values recorded on Days 28, 56, 84, and 85. Missing data were not directly imputed in this analysis; however, all non-missing data for a participant were used within the analysis to estimate the treatment effect for trough FEV1 at Day 85. Change from baseline was calculated as the value at Day 84 minus the value at Baseline.	Baseline and Day 85

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