Clinical trial NCT01879410: A Study to Compare the Efficacy and Safety of Umeclidinium/Vilanterol With Fluticasone Propionate/Salmeterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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)
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-06-17
Enrollment: 700
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change From Baseline (BL) in 0 to 24 Hour Weighted Mean Forced Expiratory Volume Over 1 Second (FEV1) at Day 84
timeFrame: Baseline and Day 84
Secondary outcomes:
measure: Change From Baseline(BL) in Trough Forced Expiratory Volume in One Second (FEV1) at Day 85
timeFrame: Baseline and Day 85
Other outcomes:
Locations:
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Newport Beach
country: United States
facility: GSK Investigational Site
state: California
city: Riverside
country: United States
facility: GSK Investigational Site
state: California
city: DeLand
country: United States
facility: GSK Investigational Site
state: Florida
city: Coeur d'Alene
country: United States
facility: GSK Investigational Site
state: Idaho
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Easley
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Seneca
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Union
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Newport News
country: United States
facility: GSK Investigational Site
state: Virginia
city: Renton
country: United States
facility: GSK Investigational Site
state: Washington
city: Temuco
country: Chile
facility: GSK Investigational Site
state: Región De La Araucania
city: Concepción
country: Chile
facility: GSK Investigational Site
state: Región Del Biobio
city: Puente Alto - Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Talca
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Talcahuano
country: Chile
facility: GSK Investigational Site
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
state: Jalisco
city: Monterrey
country: Mexico
facility: GSK Investigational Site
state: Nuevo León
city: Monterrey
country: Mexico
facility: GSK Investigational Site
state: Nuevo León
city: México DF
country: Mexico
facility: GSK Investigational Site
city: Oaxaca
country: Mexico
facility: GSK Investigational Site
city: Bergen
country: Norway
facility: GSK Investigational Site
city: Bodø
country: Norway
facility: GSK Investigational Site
city: Hamar
country: Norway
facility: GSK Investigational Site
city: Kløfta
country: Norway
facility: GSK Investigational Site
city: Stavanger
country: Norway
facility: GSK Investigational Site
city: Trondheim
country: Norway
facility: GSK Investigational Site
city: Braila
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Cluj Napoca
country: Romania
facility: GSK Investigational Site
city: Comuna Alexandru cel Bun
country: Romania
facility: GSK Investigational Site
city: Constanta
country: Romania
facility: GSK Investigational Site
city: Craiova
country: Romania
facility: GSK Investigational Site
city: Focsani
country: Romania
facility: GSK Investigational Site
city: Arkhangelsk
country: Russian Federation
facility: GSK Investigational Site
city: Barnaul
country: Russian Federation
facility: GSK Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: GSK Investigational Site
city: Chita
country: Russian Federation
facility: GSK Investigational Site
city: Ekaterinburg
country: Russian Federation
facility: GSK Investigational Site
city: Ekaterinburg
country: Russian Federation
facility: GSK Investigational Site
city: Ivanovo
country: Russian Federation
facility: GSK Investigational Site
city: Izhevsk
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Omsk
country: Russian Federation
facility: GSK Investigational Site
city: Saratov
country: Russian Federation
facility: GSK Investigational Site
city: Smolensk
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Tomsk
country: Russian Federation
facility: GSK Investigational Site
city: Ulyanovsk
country: Russian Federation
facility: GSK Investigational Site
city: Vladimir
country: Russian Federation
facility: GSK Investigational Site
city: Vladivostok
country: Russian Federation
facility: GSK Investigational Site
city: Voronezh
country: Russian Federation
facility: GSK Investigational Site
city: Yaroslavl
country: Russian Federation
facility: GSK Investigational Site
city: Yaroslavl
country: Russian Federation
facility: GSK Investigational Site
city: Yaroslavl
country: Russian Federation
facility: GSK Investigational Site
city: Meyerspark
country: South Africa
facility: GSK Investigational Site
state: Gauteng
city: Bloemfontein
country: South Africa
facility: GSK Investigational Site
city: Die Wilgers
country: South Africa
facility: GSK Investigational Site
city: Durban
country: South Africa
facility: GSK Investigational Site
city: Gatesville
country: South Africa
facility: GSK Investigational Site
city: Mowbray
country: South Africa
facility: GSK Investigational Site
city: Reiger Park
country: South Africa
facility: GSK Investigational Site
city: Somerset West
country: South Africa
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.