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)

This study has been completed.
Information provided by (Responsible Party):
ClinicalTrials.gov Identifier:
First received: March 28, 2013
Last updated: March 31, 2014
Last verified: March 2014

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.

Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: Umeclidinium bromide/Vilanterol
Drug: Fluticasone propionate/Salmeterol
Drug: Placebo NDPI
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: DB2116134: A Randomized, Multi-center, Double-blind, Double-dummy, Parallel Group Study to Evaluate the Efficacy and Safety of Umeclidinium Bromide/Vilanterol Compared With Fluticasone Propionate/Salmeterol Over 12 Weeks in Subjects With COPD

Resource links provided by NLM:

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 24-hour weighted-mean FEV1 at Day 84 [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
    Serial spirometry will be performed. Weighted mean will be calculated from the pre-dose FEV1 (23 and 24 hours after the previous day's dose) and post-dose FEV1 measurements at 5 and 15 minutes and 1, 3, 6, 9, 12 (pre-evening dose), 13, 15, 18, 23, and 24 hours after the morning dose.

Secondary Outcome Measures:
  • Trough FEV1 [ Time Frame: Day 85 ] [ Designated as safety issue: No ]
    Trough FEV1 defined as the mean of the FEV1 values obtained 23 and 24 hours after morning dosing on Day 84.

Enrollment: 717
Study Start Date: April 2013
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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).
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).
Active Comparator: 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.
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).
Drug: Placebo NDPI
Dry white powder of matching placebo as NDPI with 30 doses (2 strips with 30 blisters per strip).


Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01822899

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Sponsors and Collaborators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01822899     History of Changes
Other Study ID Numbers: 116134
Study First Received: March 28, 2013
Last Updated: March 31, 2014
Health Authority: Russian Federation: Ministry of Health of Russia of Federation.
Spain: Agencia Espanola de Medicamentos y Productos Sanitarios
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines, National Institute of Pharmacy
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Denmark: The Danish Health and Medicines Authority, Kliniske forsøg Axel Heides Gade 1 2300 København S
Czech Republic: State Institute for Drug Control
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
Netherlands: CCMO (Centrale Commissie Mensgebonden Onderzoek) (=central committee for human related research)

Keywords provided by GlaxoSmithKline:
Novel Dry Powder Inhaler (NDPI)
umeclidinium bromide (UMEC)
lung function
salmeterol (SAL)
fluticasone propionate (FP)
vilanterol (VI)
Chronic obstructive pulmonary disease

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Disease Attributes
Respiratory Tract Diseases
Pathologic Processes
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 15, 2014