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

NCT ID: NCT01772134

Last Updated: 2018-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 617 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-01
• Study Completion Date: 2013-07-22

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.

Detailed Description

This is a mutlicenter, randomized, double-blind, parallell-group study. Subejcts who meet the eligibility criteria at screening and meet the randomization criteria at the end of a 4 week run-in period will enter a 12 week treatment period. There will be a 7 day follow-up period after the treatment period.

Conditions

Pulmonary Disease, Chronic Obstructive

Study Design

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

Study Groups

Umeclidinium bromide 62.5 + Fluticasone propionate/Salmeterol

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

Group Type: EXPERIMENTAL

Umeclidinium bromide 62.5mcg

Intervention Type: DRUG

Inhalation Powder, LAMA 62.5mcg

Fluticasone propionate 250mcg/Salmeterol 50mcg

Intervention Type: DRUG

Inhalation Powder, ICS/LABA

Umeclidinium bromide 125 + Fluticasone propionate/Salmeterol

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

Group Type: ACTIVE_COMPARATOR

Umeclidinium bromide 125mcg

Intervention Type: DRUG

Inhalation Powder, LAMA 125mcg

Fluticasone propionate 250mcg/Salmeterol 50mcg

Intervention Type: DRUG

Inhalation Powder, ICS/LABA

Placebo + Fluticasone propionate/Salmeterol

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

Group Type: PLACEBO_COMPARATOR

Fluticasone propionate 250mcg/Salmeterol 50mcg

Intervention Type: DRUG

Inhalation Powder, ICS/LABA

Placebo

Intervention Type: DRUG

Inhalation Powder, Placebo

Interventions

Umeclidinium bromide 62.5mcg

Inhalation Powder, LAMA 62.5mcg

Intervention Type: DRUG

Umeclidinium bromide 125mcg

Inhalation Powder, LAMA 125mcg

Intervention Type: DRUG

Fluticasone propionate 250mcg/Salmeterol 50mcg

Inhalation Powder, ICS/LABA

Intervention Type: DRUG

Placebo

Inhalation Powder, Placebo

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 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.

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 α-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 conditions in addition to COPD should be excluded. Examples may include clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or interstitial lung disease.
• 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: 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.
• 12-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.
• 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., 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.

• 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

Jasper, Alabama, United States

GSK Investigational Site

Clearwater, Florida, United States

GSK Investigational Site

Ormond Beach, Florida, United States

GSK Investigational Site

Lafayette, Indiana, United States

GSK Investigational Site

New Orleans, Louisiana, United States

GSK Investigational Site

Edina, Minnesota, United States

GSK Investigational Site

St Louis, Missouri, United States

GSK Investigational Site

Medford, Oregon, United States

GSK Investigational Site

Easley, South Carolina, United States

GSK Investigational Site

Greenville, South Carolina, United States

GSK Investigational Site

Union, South Carolina, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

Morgantown, West Virginia, United States

GSK Investigational Site

Vancouver, British Columbia, Canada

GSK Investigational Site

Winnipeg, Manitoba, Canada

GSK Investigational Site

Bay Roberts, Newfoundland and Labrador, Canada

GSK Investigational Site

Truro, Nova Scotia, Canada

GSK Investigational Site

Burlington, Ontario, Canada

GSK Investigational Site

Greater Sudbury, Ontario, Canada

GSK Investigational Site

Sarnia, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Gatineau, Quebec, Canada

GSK Investigational Site

Mirabel, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Québec, Quebec, Canada

GSK Investigational Site

Québec, Quebec, Canada

GSK Investigational Site

Saint Romuald, Quebec, Canada

GSK Investigational Site

Saint-Charles-Borromée, Quebec, Canada

GSK Investigational Site

Trois-Rivières, Quebec, Canada

GSK Investigational Site

Sinsheim, Baden-Wurttemberg, Germany

GSK Investigational Site

Stuttgart, Baden-Wurttemberg, Germany

GSK Investigational Site

Bamberg, Bavaria, Germany

GSK Investigational Site

Schwabach, Bavaria, Germany

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Gelnhausen, Hesse, Germany

GSK Investigational Site

Kassel, Hesse, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Weyhe-Leeste, Lower Saxony, Germany

GSK Investigational Site

Schwerin, Mecklenburg-Vorpommern, Germany

GSK Investigational Site

Cologne, North Rhine-Westphalia, Germany

GSK Investigational Site

Düren, North Rhine-Westphalia, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Goch, North Rhine-Westphalia, Germany

GSK Investigational Site

Witten, North Rhine-Westphalia, Germany

GSK Investigational Site

Koblenz, Rhineland-Palatinate, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Leipzg, Saxony, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Magdeburg, Saxony-Anhalt, Germany

GSK Investigational Site

Teuchern, Saxony-Anhalt, Germany

GSK Investigational Site

Lübeck, Schleswig-Holstein, Germany

GSK Investigational Site

Reinfeld, Schleswig-Holstein, Germany

GSK Investigational Site

Gera, Thuringia, Germany

GSK Investigational Site

Schmölln, Thuringia, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Bucheon-si, , South Korea

GSK Investigational Site

Cheongju, Chungcheongbuk-do, , South Korea

GSK Investigational Site

Kangwon-do, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Suwon, Gyeonggi-do, , South Korea

Countries

United States; Canada; Germany; South Korea

Study Documents

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

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

Other Identifiers

116135

Identifier Type: -

Identifier Source: org_study_id