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

A Multicenter, Randomized, Double-blind, Parallelgroup Study to Evaluate the Efficacy and Safety of the Addition of Umeclidinium Bromide Inhalation Powder (62.5mcg) Once-daily to Fluticasone Propionate/Salmeterol (250/50mcg) Twice-daily, Umeclidinium Bromide Inhalation Powder (125mcg) Once-daily to Fluticasone Propionate/Salmeterol (250/50mcg) Twice-daily Versus Placebo to Fluticasone Propionate/Salmeterol (250/50mcg) Twice-daily Over 12 Weeks in Subjects With COPD.

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

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Umeclidinium bromide 62.5mcg; Drug: Umeclidinium bromide 125mcg; Drug: Fluticasone propionate 250mcg/Salmeterol 50mcg

Detailed Description

This is a multicenter, randomized, double-blind, parallel-group study. Subjects 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.

• Study Type: Interventional
• Enrollment (Actual): 608
• Phase: Phase 3

Contacts and Locations

Study Locations

• Chile
  • Región Del Biobio
    • Concepción, Región Del Biobio, Chile, 4070038
      • GSK Investigational Site
  • Región Metro De Santiago
    • Puente Alto - Santiago, Región Metro De Santiago, Chile, 8207257
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile, 7500710
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile, 7500800
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile, 8880465
      • GSK Investigational Site
    • Talca, Región Metro De Santiago, Chile, 3460001
      • GSK Investigational Site
  • Valparaíso
    • Viña del Mar, Valparaíso, Chile
      • GSK Investigational Site
    • Viña del Mar, Valparaíso, Chile, 2520024
      • GSK Investigational Site
• Czech Republic
  • Karlovy Vary, Czech Republic, 360 09
    • GSK Investigational Site
  • Kralupy nad Vltavou, Czech Republic, 278 01
    • GSK Investigational Site
  • Lovosice, Czech Republic, 410 02
    • GSK Investigational Site
  • Olomouc, Czech Republic, 772 00
    • GSK Investigational Site
  • Ostrava - Poruba, Czech Republic, 70868
    • GSK Investigational Site
  • Plzen, Czech Republic, 301 00
    • GSK Investigational Site
  • Plzen, Czech Republic, 323 00
    • GSK Investigational Site
  • Praha 4, Czech Republic, 140 46
    • GSK Investigational Site
  • Praha 5, Czech Republic, 150 00
    • GSK Investigational Site
  • Praha 7, Czech Republic, 170 00
    • GSK Investigational Site
  • Tabor, Czech Republic, 390 19
    • GSK Investigational Site
  • Teplice, Czech Republic, 415 10
    • GSK Investigational Site
• Korea, Republic of
  • Daegu, Korea, Republic of, 705-717
    • GSK Investigational Site
  • Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 110-744
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 143-729
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 152-703
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 130-848
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 134-701
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 158-710
    • GSK Investigational Site
• Poland
  • Elblag, Poland, 82-300
    • GSK Investigational Site
  • Gdynia, Poland, 81-384
    • GSK Investigational Site
  • Grudziadz, Poland, 86-300
    • GSK Investigational Site
  • Inowroclaw, Poland, 88-100
    • GSK Investigational Site
  • Krakow, Poland, 31-024
    • GSK Investigational Site
  • Ostrow Wielkopolski, Poland, 63-400
    • GSK Investigational Site
  • Pila, Poland, 64-920
    • GSK Investigational Site
  • Warszawa, Poland, 01-192
    • GSK Investigational Site
  • Wroclaw, Poland, 50-088
    • GSK Investigational Site
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • GSK Investigational Site
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • GSK Investigational Site
  • California
    • Huntington Beach, California, United States, 92647
      • GSK Investigational Site
  • Florida
    • DeLand, Florida, United States, 32720
      • GSK Investigational Site
    • Orlando, Florida, United States, 32822
      • GSK Investigational Site
    • Tampa, Florida, United States, 33603
      • GSK Investigational Site
  • Idaho
    • Coeur D'Alene, Idaho, United States, 83814
      • GSK Investigational Site
  • Louisiana
    • Sunset, Louisiana, United States, 70584
      • GSK Investigational Site
  • Missouri
    • St. Charles, Missouri, United States, 63301
      • GSK Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45245
      • GSK Investigational Site
  • South Carolina
    • Rock Hill, South Carolina, United States, 29732
      • GSK Investigational Site
    • Seneca, South Carolina, United States, 29678
      • GSK Investigational Site
    • Spartanburg, South Carolina, United States, 29303
      • GSK Investigational Site
  • Virginia
    • Newport News, Virginia, United States, 23606
      • GSK Investigational Site
    • Richmond, Virginia, United States, 23249
      • GSK Investigational Site
    • Richmond, Virginia, United States, 23229
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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-child-bearing potential, or if of child bearing potential, has a megative serum pregnancy test at screening, and agrees to one of the acceptable contraceptive methods listed 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.
• 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 certain medications for the protocol-specific times prior 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Umeclidinium bromide; Long-acting muscarinic antagonist (LAMA)	Drug: Umeclidinium bromide 62.5mcg; Inhalation powder; Drug: Umeclidinium bromide 125mcg; Inhalation powder
Active Comparator: Fluticasone propionate/Salmeterol; Inhaled corticosteroid (ICS)/Long-acting beta agonist (LABA)	Drug: Fluticasone propionate 250mcg/Salmeterol 50mcg; Inhalation powder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weighted Mean 0-6 Hour FEV1 Obtained Post-dose 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 FEV1 was derived by calculating the area under the curve, and then dividing the value by the relevant time interval. The weighted mean was calculated using the 6-hour serial FEV1 measurements at Day 84, which included pre-dose, and post-dose at 15 min, 30 min, 1 hour, 3 hours, and 6 hours. Baseline trough FEV1 is the mean of the two assessments made at -30 and -5 min pre-dose on Treatment Day 1. Change from Baseline was calculated as the Day 84 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 -30and -5 min pre-dose on Treatment Day 1), smoking status, day, day by Baseline, and day by treatment interactions.	Baseline and Day 84
Change From Baseline in the Mean Percentage of Rescue-free Days Over Weeks 1-12	A rescue-free day is defined as a day on which no rescue medication was taken. Baseline calculations include a period of the later of 27 days before Visit 2 and the day after Visit 1, up to and including Day 1. The Weeks 1-12 calculations include a period from Study Day 2 up to the earlier of Study Day 85 and the day before Visit 7. Change from Baseline was calculated as the Weeks 1-12 value minus the Baseline value.	Baseline and Weeks 1- 12
Change From Baseline in the Mean Number of Puffs Per Day of Rescue Albuterol/Salbutamol Over Weeks 1-12	The mean number of puffs per day of rescue albuterol/salbutamol at Baseline and on-treatment was recorded. The total puffs of rescue albuterol/salbutamol for each day was calculated as: (number of puffs + [2 * number of nebules]). Baseline calculations include a period of the later of 27 days before Visit 2 and the day after Visit 1, up to and including Day 1. The Weeks 1-12 calculations include a period from Study Day 2 up to the earlier of Study Day 85 and the day before Visit 7. Change from Baseline was calculated as the Weeks 1-12 value minus the Baseline value. Analysis was performed using an analysis of covariance (ANCOVA) model with covariates of treatment, Baseline (mean during the 4 weeks prior to Day 1), and smoking status.	Baseline and Weeks1- 12

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: January 17, 2013
• First Submitted That Met QC Criteria: January 17, 2013
• First Posted (Estimate): January 21, 2013

Study Record Updates

• Last Update Posted (Actual): March 23, 2017
• Last Update Submitted That Met QC Criteria: March 21, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Adrenergic Agonists; Dermatologic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Fluticasone; Xhance; Salmeterol Xinafoate; Bromides
• Other Study ID Numbers: 116136

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Informed Consent Form
   Information identifier: 116136
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: 116136
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 116136
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: 116136
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Annotated Case Report Form
   Information identifier: 116136
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 116136
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Statistical Analysis Plan
   Information identifier: 116136
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register