Efficacy and Safety of the Addition of Fluticanse Propionate/Salmeterol (250/50mcg) Twice-daily to 2 Doses of Umeclidinium Bromide (62.5 or 125mcg) Once-daily Over 12 Weeks

NCT01772134 | Completed Phase 3 Results

• 1 other identifier: 116135
• Study Type: interventional
• Target: 617
• Locations: 4 countries
• Sites: 73

Brief Summary

The purpose of this 12 week study is to evaluate the effects of the addition of umeclidinium bromide (62.5mcg) once-daily to fluticanse propionate/salmeterol (250/50mcg) twice-daily, umeclidinium bromide (125mcg) once-daily to fluticanse propionate/salmeterol (250/50mcg) twice-daily versus placebo to fluticanse propionate/salmeterol (250/50mcg) twice-daily on lung function, COPD-related health status assessments and safety in COPD subjects.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Trough Forced Expiratory Volume in One Second (FEV1) on 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. Trough FEV1 on Treatment Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Treatment Day 84 (i.e., at Week 12). Baseline trough FEV1 is the mean of the two assessments made at -30 and -5 minutes (min) pre-dose on Treatment Day 1. Change from Baseline was calculated as the Day 85 value minus the Baseline value. Analysis was performed using a repeated measures model with covariates of treatment, Baseline (mean of the two assessments made at -30 and -5 min pre-dose on Treatment Day 1), smoking status, day, day by Baseline and day by treatment interactions.

  Baseline and Day 85

Secondary Outcomes (3)

• Change From Baseline in Weighted Mean 0-6 Hour FEV1 Obtained Post-dose at Day 84

  Baseline and Day 84

• Change From Baseline in the Mean Percentage of Rescue-free Days Over Weeks 1-12

  Baseline and Weeks 1-12

• Change From Baseline in the Mean Number of Puffs Per Day of Rescue Albuterol/Salbutamol Over Weeks 1-12

  Baseline and Weeks 1-12

Study Arms (3)

Umeclidinium bromide 62.5 + Fluticasone propionate/Salmeterol

EXPERIMENTAL

Long-acting muscarinic antagonist (LAMA), 62.5mcg plus Inhaled corticosteriod (ICS), 250mcg/ Long acting Beta agonist (LABA), 50mcg

Drug: Umeclidinium bromide 62.5mcg; Drug: Fluticasone propionate 250mcg/Salmeterol 50mcg

Umeclidinium bromide 125 + Fluticasone propionate/Salmeterol

ACTIVE COMPARATOR

Long-acting muscarinic antagonist (LAMA), 125mcg plus Inhaled corticosteriod (ICS), 250mcg/ Long acting Beta agonist (LABA), 50mcg

Drug: Umeclidinium bromide 125mcg; Drug: Fluticasone propionate 250mcg/Salmeterol 50mcg

Placebo + Fluticasone propionate/Salmeterol

PLACEBO COMPARATOR

Inhaled corticosteriod (ICS), 250mcg/ Long acting Beta agonist (LABA), 50mcg

Drug: Fluticasone propionate 250mcg/Salmeterol 50mcg; Drug: Placebo

Interventions

Umeclidinium bromide 62.5mcg DRUG

Inhalation Powder, LAMA 62.5mcg

Umeclidinium bromide 62.5 + Fluticasone propionate/Salmeterol

Umeclidinium bromide 125mcg DRUG

Inhalation Powder, LAMA 125mcg

Umeclidinium bromide 125 + Fluticasone propionate/Salmeterol

Fluticasone propionate 250mcg/Salmeterol 50mcg DRUG

Inhalation Powder, ICS/LABA

Placebo + Fluticasone propionate/Salmeterol; Umeclidinium bromide 125 + Fluticasone propionate/Salmeterol; Umeclidinium bromide 62.5 + Fluticasone propionate/Salmeterol

Placebo DRUG

Inhalation Powder, Placebo

Placebo + Fluticasone propionate/Salmeterol

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 if of non-childbearing potential, or if of child bearing potential, has a negative serum pregnancy test at screening, and agrees to one of the acceptable contraceptive methods listed in the protocol, used consistenty and correctly.
• Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society.
• Smoking History: Current or former cigarette smokers with a history of cigarette smoking of ≥10 pack-years \[number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)\]. Former 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-albuterol/salbutamol FEV1/FVC ratio of \<0.70 and a pre and post-albuterol/salbutamol FEV1 of ≤70% of predicted normal values at Visit 1 (Screening) calculated using Nutrition Health and Examination Survey (NHANES) III reference equations.
• Dyspnea: A score of ≥2 on the mMRC Dyspnea Scale at Visit 1.

You may not qualify if:

• Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
• Asthma: A current diagnosis of asthma.
• Contraindications: Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, sympathomimetic, corticosteroid (intranasal, inhaled or systemic) 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 anticholingeric.
• Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
• Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Visit 1.
• Lead 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.
• Specific ECG findings that preclude subject eligibility are listed in Appendix 4. The study investigator will determine the medical significance of any ECG abnormalities not listed in Appendix 4.
• Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
• Medications Prior to Screening: Use of the medications listed in the protocol according to protocol-specific times prio to visit 1.
• Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (e.g., albuterol/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, subinvestigator, study coordinator, or employee of the participating investigator.
• Inability to read: In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete a questionnaire.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (73)

GSK Investigational Site

Jasper, Alabama, 35501, United States

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GSK Investigational Site

Clearwater, Florida, 33765, United States

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GSK Investigational Site

Ormond Beach, Florida, 32174, United States

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GSK Investigational Site

Lafayette, Indiana, 47904, United States

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GSK Investigational Site

New Orleans, Louisiana, 70115, United States

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GSK Investigational Site

Edina, Minnesota, 55435, United States

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GSK Investigational Site

St Louis, Missouri, 63141, United States

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GSK Investigational Site

Medford, Oregon, 97504, United States

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GSK Investigational Site

Easley, South Carolina, 29640, United States

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GSK Investigational Site

Greenville, South Carolina, 29615, United States

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GSK Investigational Site

Union, South Carolina, 29379, United States

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GSK Investigational Site

San Antonio, Texas, 78229, United States

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GSK Investigational Site

Morgantown, West Virginia, 26505, United States

Location

GSK Investigational Site

Vancouver, British Columbia, V6J 1S3, Canada

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GSK Investigational Site

Winnipeg, Manitoba, R2K 3S8, Canada

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GSK Investigational Site

Bay Roberts, Newfoundland and Labrador, A0A 1G0, Canada

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GSK Investigational Site

Truro, Nova Scotia, B2N 1L2, Canada

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GSK Investigational Site

Burlington, Ontario, L7N 3V2, Canada

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GSK Investigational Site

Greater Sudbury, Ontario, P3E 1H5, Canada

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GSK Investigational Site

Sarnia, Ontario, N7T 4X3, Canada

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GSK Investigational Site

Toronto, Ontario, M5G 1N8, Canada

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GSK Investigational Site

Toronto, Ontario, M9W 4L6, Canada

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GSK Investigational Site

Gatineau, Quebec, J8Y 6S8, Canada

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GSK Investigational Site

Mirabel, Quebec, J7J 2K8, Canada

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GSK Investigational Site

Montreal, Quebec, H2R 1V6, Canada

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GSK Investigational Site

Québec, Quebec, G1V 4G5, Canada

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GSK Investigational Site

Québec, Quebec, G3K 2P8, Canada

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GSK Investigational Site

Saint Romuald, Quebec, G6W 5M6, Canada

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GSK Investigational Site

Saint-Charles-Borromée, Quebec, J6E 2B4, Canada

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GSK Investigational Site

Trois-Rivières, Quebec, G8T 7A1, Canada

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GSK Investigational Site

Sinsheim, Baden-Wurttemberg, 74889, Germany

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GSK Investigational Site

Stuttgart, Baden-Wurttemberg, 70378, Germany

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GSK Investigational Site

Bamberg, Bavaria, 96049, Germany

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GSK Investigational Site

Schwabach, Bavaria, 91126, Germany

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GSK Investigational Site

Frankfurt am Main, Hesse, 60389, Germany

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GSK Investigational Site

Gelnhausen, Hesse, 63571, Germany

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GSK Investigational Site

Kassel, Hesse, 34121, Germany

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GSK Investigational Site

Hanover, Lower Saxony, 30159, Germany

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GSK Investigational Site

Hanover, Lower Saxony, 30173, Germany

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GSK Investigational Site

Weyhe-Leeste, Lower Saxony, 28844, Germany

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GSK Investigational Site

Schwerin, Mecklenburg-Vorpommern, 19055, Germany

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GSK Investigational Site

Cologne, North Rhine-Westphalia, 51069, Germany

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GSK Investigational Site

Düren, North Rhine-Westphalia, 52349, Germany

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GSK Investigational Site

Essen, North Rhine-Westphalia, 45355, Germany

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GSK Investigational Site

Essen, North Rhine-Westphalia, 45359, Germany

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GSK Investigational Site

Goch, North Rhine-Westphalia, 47574, Germany

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GSK Investigational Site

Witten, North Rhine-Westphalia, 58452, Germany

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GSK Investigational Site

Koblenz, Rhineland-Palatinate, 56068, Germany

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GSK Investigational Site

Dresden, Saxony, 01069, Germany

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GSK Investigational Site

Leipzg, Saxony, 04109, Germany

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GSK Investigational Site

Leipzig, Saxony, 04103, Germany

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GSK Investigational Site

Leipzig, Saxony, 04207, Germany

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GSK Investigational Site

Leipzig, Saxony, 04357, Germany

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GSK Investigational Site

Magdeburg, Saxony-Anhalt, 39112, Germany

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GSK Investigational Site

Teuchern, Saxony-Anhalt, 6682, Germany

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GSK Investigational Site

Lübeck, Schleswig-Holstein, 23552, Germany

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GSK Investigational Site

Reinfeld, Schleswig-Holstein, 23858, Germany

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GSK Investigational Site

Gera, Thuringia, 07548, Germany

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GSK Investigational Site

Schmölln, Thuringia, 04626, Germany

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GSK Investigational Site

Berlin, 13125, Germany

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GSK Investigational Site

Berlin, 13156, Germany

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GSK Investigational Site

Berlin, 14059, Germany

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GSK Investigational Site

Hamburg, 22143, Germany

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GSK Investigational Site

Hamburg, 22299, Germany

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GSK Investigational Site

Hamburg, 22767, Germany

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GSK Investigational Site

Bucheon-si, 420-767, South Korea

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GSK Investigational Site

Cheongju, Chungcheongbuk-do, 361-711, South Korea

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GSK Investigational Site

Kangwon-do, 220-701, South Korea

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GSK Investigational Site

Seoul, 130-872, South Korea

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GSK Investigational Site

Seoul, 136-705, South Korea

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GSK Investigational Site

Seoul, 137-701, South Korea

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GSK Investigational Site

Seoul, 156-707, South Korea

Location

GSK Investigational Site

Suwon, Gyeonggi-do, 442-723, South Korea

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Fluticasone; Salmeterol Xinafoate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2013
• First Posted: January 21, 2013
• Study Start: January 1, 2013
• Primary Completion: July 1, 2013
• Study Completion: July 22, 2013
• Last Updated: January 29, 2018
• Results First Posted: April 16, 2014

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will share

Locations

DE (35); US (13); CA (17); KR (8)