Study Evaluating the 24-Hour Pulmonary Function Profile of Fluticasone Furoate (FF) /GW642444 (Vilanterol) (VI) Inhalation Powder 100/25mcg Once Daily Compared With Fluticasone Propionate/Salmeterol Inhalation Powder 250/50mcg Twice Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

A 12-week Study to Evaluate the 24-hour Pulmonary Function Profile of Fluticasone Furoate/Vilanterol (FF/VI) Inhalation Powder 100/25 mcg Once Daily Compared With Fluticasone Propionate/Salmeterol Inhalation Powder 250/50 mcg Twice Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

The purpose of this study is to evaluate the 24-hour spirometry effect (FEV1) of FF/VI 100/25mcg once daily compared with Fluticasone Propionate/Salmeterol 250/50mcg twice daily over a 12-week treatment period in subjects with COPD.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Fluticasone Furoate 100mcg/ GW642444 (vilanterol) 25mcg; Drug: Double-dummy placebo; Drug: Salbutamol as needed; Drug: Fluticasone Propionate 250mcg / salmeterol 50mcg

Detailed Description

This is a randomized, double-blind, double-dummy, multi-centre parallel group study. Subjects who meet the eligibility criteria at Screening and meet the randomization criteria at the end of a 2-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): 512
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Schleswig-Holstein
    • Luebeck, Schleswig-Holstein, Germany, 23552
      • GSK Investigational Site
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • GSK Investigational Site
    • San Felice A Cancello Caserta, Campania, Italy, 81027
      • GSK Investigational Site
    • Telese Terme (BN), Campania, Italy, 82037
      • GSK Investigational Site
  • Emilia-Romagna
    • Parma, Emilia-Romagna, Italy, 43100
      • GSK Investigational Site
  • Lazio
    • Roma, Lazio, Italy, 00185
      • GSK Investigational Site
  • Lombardia
    • Rozzano (MI), Lombardia, Italy, 20089
      • GSK Investigational Site
  • Marche
    • Torrette (AN), Marche, Italy, 60126
      • GSK Investigational Site
  • Sardegna
    • Cagliari, Sardegna, Italy, 09126
      • GSK Investigational Site
  • Sicilia
    • Palermo, Sicilia, Italy, 90146
      • GSK Investigational Site
  • Toscana
    • Firenze, Toscana, Italy, 50134
      • GSK Investigational Site
  • Veneto
    • Padova, Veneto, Italy, 35128
      • GSK Investigational Site
• South Africa
  • Bellville, South Africa, 7531
    • GSK Investigational Site
  • Bloemfontein, South Africa, 9301
    • GSK Investigational Site
  • Cape Town, South Africa, 7572
    • GSK Investigational Site
  • George, South Africa, 6529
    • GSK Investigational Site
  • Port Elizabeth, South Africa, 6045
    • GSK Investigational Site
  • Reiger Park, South Africa, 1459
    • GSK Investigational Site
  • Somerset West, South Africa, 7130
    • GSK Investigational Site
  • Thabazimbi, South Africa, 0380
    • GSK Investigational Site
  • Witbank, South Africa, 1034
    • GSK Investigational Site
  • Gauteng
    • Benoni, Gauteng, South Africa, 1501
      • GSK Investigational Site
• Spain
  • Alicante, Spain, 03114
    • GSK Investigational Site
  • Córdoba, Spain, 14004
    • GSK Investigational Site
  • Lugo, Spain, 27003
    • GSK Investigational Site
  • Mérida (Badajoz), Spain, 06800
    • GSK Investigational Site
  • Ponferrada (León), Spain, 24411
    • GSK Investigational Site
  • Valladolid, Spain, 47005
    • GSK Investigational Site
• Ukraine
  • Cherkassy, Ukraine, 18009
    • GSK Investigational Site
  • Donetsk, Ukraine, 83099
    • GSK Investigational Site
  • Kharkiv, Ukraine, 61002
    • GSK Investigational Site
  • Kharkiv, Ukraine, 61035
    • GSK Investigational Site
  • Kiev, Ukraine, 03680
    • GSK Investigational Site
  • Kyiv, Ukraine, 03038
    • GSK Investigational Site
  • Kyiv, Ukraine, 03049
    • GSK Investigational Site
  • Kyiv, Ukraine, 04107
    • GSK Investigational Site
  • Mykolayiv, Ukraine, 54003
    • GSK Investigational Site
  • Vinnytsia, Ukraine, 21018
    • GSK Investigational Site
• United States
  • Alabama
    • Jasper, Alabama, United States, 35501
      • GSK Investigational Site
  • California
    • Riverside, California, United States, 92506
      • GSK Investigational Site
  • Florida
    • DeLand, Florida, United States, 32720
      • GSK Investigational Site
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • GSK Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • GSK Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • GSK Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • GSK Investigational Site
  • South Carolina
    • Gaffney, South Carolina, United States, 29340
      • GSK Investigational Site
    • Orangeburg, South Carolina, United States, 29118
      • GSK Investigational Site
    • Seneca, South Carolina, United States, 29678
      • GSK Investigational Site
    • Spartanburg, South Carolina, United States, 29303
      • GSK Investigational Site
  • Texas
    • Boerne, Texas, United States, 78006
      • 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:

• Signed and dated written informed consent
• Male or females ≥ 40 years of age
• Established clinical history of COPD by ATS/ERS definition
• Females are 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 protocol, used consistently and correctly
• Former or current smoker > 10 pack years
• Post-albuterol spirometry criteria: FEV1/FVC ratio ≤ 0.70 and FEV1 ≤ 70% of predicted normal (NHANES III)

Exclusion Criteria:

• Current diagnosis of asthma
• Subjects with other respiratory disorders including active tuberculosis, α1-antitrypsin deficiency, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases
• Lung volume reduction surgery within previous 12 months
• Clinically significant abnormalities not due to COPD by chest x-ray
• Hospitalized for poorly controlled COPD within 12 weeks of Screening
• Poorly controlled COPD 6 weeks prior to Screening, defined as acute worsening of COPD that is managed by the subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician
• Lower respiratory infection requiring antibiotics 6 weeks prior to Screening
• Uncontrolled or clinically significant (in opinion of PI) cardiovascular, hypertension, neurological, psychiatric, renal, hepatic, immunological, endocrine, peptic ulcer disease, or hematological abnormalities
• Carcinoma not in complete remission for at least 5 years
• Subjects with history of hypersensitivity to study medications (e.g., beta-agonists, corticosteroid) or components of inhalation powder (e.g., lactose, magnesium stearate)
• Subjects with history of severe milk protein allergy that, in opinion of study physician, contraindicates subject's participation
• Known/suspected history of alcohol or drug abuse in the last 2 years
• Women who are pregnant or lactating or plan to become pregnant
• Subjects medically unable to withhold albuterol and/or ipratropium 4 hours prior to spirometry testing at each study visit
• Use of certain medications such as bronchodilators and corticosteroids for the protocol-specific times prior to Visit 1 (the Investigator will discuss the specific medications)
• Long Term Oxygen Therapy (LTOT) or nocturnal oxygen therapy >12 hours a day
• Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening or during the study
• Non-compliance or inability to comply with study procedures or scheduled visits
• Affiliation with investigator site

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: Fluticasone Furoate / GW642444 (vilanterol); Inhaled Corticosteroid (ICS)/ Long acting Beta Agonist (LABA)	Drug: Fluticasone Furoate 100mcg/ GW642444 (vilanterol) 25mcg; inhalation powder; Drug: Double-dummy placebo; inhalation powder; Drug: Salbutamol as needed; inhalation powder
Active Comparator: Fluticasone Propionate / salmeterol; Inhaled Corticosteroid (ICS)/ Long acting Beta Agonist (LABA)	Drug: Double-dummy placebo; inhalation powder; Drug: Salbutamol as needed; inhalation powder; 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 Trough in 24-Hour Weighted Mean FEV1 on Treatment Day 84	Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled in one second. The weighted mean was calculated from the pre-dose FEV1 and the post-dose FEV1 measurements at 5, 15, 30, and 60 minutes (min) and 2, 4, 6, 8, 12, 13, 14, 16, 20, and 24 hours post-dose on Treatment Day 84. Baseline trough FEV1 was calculated as the mean of the two assessments made 30 and 5 minutes pre-dose on Treatment Day 1. Change from Baseline was calculated as the average of the Day 84 values minus the Baseline value. Analysis of covariance (ANCOVA) was conducted with covariates for country, smoking status, reversibility, and Baseline FEV1.	Baseline (Day 1) and Day 84

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Onset on Treatment Day 1	Time to onset on Treatment Day 1 is defined as the time to an increase of 100 milliliters (mL) from Baseline in FEV1. Time to onset was calculated over 0 to 4 hours (5 min, 15 min, 30 min, 60 min, 120 min, and 240 min) post-dose.	Baseline and Day 1

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Dransfield MT, Feldman G, Korenblat P, LaForce CF, Locantore N, Pistolesi M, Watkins ML, Crim C, Martinez FJ. Efficacy and safety of once-daily fluticasone furoate/vilanterol (100/25 mcg) versus twice-daily fluticasone propionate/salmeterol (250/50 mcg) in COPD patients. Respir Med. 2014 Aug;108(8):1171-9. doi: 10.1016/j.rmed.2014.05.008. Epub 2014 Jun 19.

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: March 18, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 24, 2012

Study Registration Dates

• First Submitted: March 17, 2011
• First Submitted That Met QC Criteria: March 24, 2011
• First Posted (Estimate): March 25, 2011

Study Record Updates

• Last Update Posted (Actual): February 15, 2018
• Last Update Submitted That Met QC Criteria: January 18, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Aspiration; 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; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Fluticasone; Xhance; Albuterol; Salmeterol Xinafoate
• Other Study ID Numbers: 112352

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. Statistical Analysis Plan
   Information identifier: 112352
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 112352
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 112352
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: 112352
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 112352
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 112352
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: 112352
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register