A 24-week Arterial Stiffness Study With Fluticasone Furoate/Vilanterol in COPD

A 24-week Study to Evaluate the Effect of Fluticasone Furoate/Vilanterol 100/25 mcg Inhalation Powder Delivered Once-daily Via a Novel Dry Powder Inhaler on Arterial Stiffness Compared With Placebo and Vilanterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD).

The purpose of the study is to investigate the effect of fluticasone furoate/vilanterol Inhalation Powder on arterial stiffness compared with placebo and vilanterol over a 24-week treatment period in subjects with COPD and aortic pulse wave velocity of 11.0 m/s or above.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Placebo; Drug: Fluticasone Furoate/Vilanterol; Drug: Vilanterol

• Study Type: Interventional
• Enrollment (Actual): 446
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10717
    • GSK Investigational Site
  • Berlin, Germany, 10787
    • GSK Investigational Site
  • Berlin, Germany, 10789
    • GSK Investigational Site
  • Hamburg, Germany, 20253
    • GSK Investigational Site
  • Brandenburg
    • Elsterwerda, Brandenburg, Germany, 04910
      • GSK Investigational Site
  • Hessen
    • Frankfurt, Hessen, Germany, 60596
      • GSK Investigational Site
  • Sachsen
    • Dresden, Sachsen, Germany, 01069
      • GSK Investigational Site
    • Leipzg, Sachsen, Germany, 04109
      • GSK Investigational Site
  • Sachsen-Anhalt
    • Magdeburg, Sachsen-Anhalt, Germany, 39112
      • GSK Investigational Site
  • Schleswig-Holstein
    • Geesthacht, Schleswig-Holstein, Germany, 21502
      • GSK Investigational Site
    • Luebeck, Schleswig-Holstein, Germany, 23552
      • GSK Investigational Site
• Korea, Republic of
  • Ansan, Korea, Republic of, 425-707
    • GSK Investigational Site
  • Gwangju, Korea, Republic of, 501-757
    • GSK Investigational Site
  • Ilsanseo-gu, Goyang-si, Gyeonggi-do, Korea, Republic of, 411706
    • GSK Investigational Site
  • Pusan, Korea, Republic of, 614-735
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 137-701
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 152-703
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 134-090
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 134060
    • GSK Investigational Site
• Norway
  • Elverum, Norway, 2408
    • GSK Investigational Site
  • Kløfta, Norway, 2040
    • GSK Investigational Site
  • Moss, Norway, 1501
    • GSK Investigational Site
  • Stavanger, Norway, 4005
    • GSK Investigational Site
• Philippines
  • Dagupan City, Philippines, 2400
    • GSK Investigational Site
  • Jaro, Iloilo City, Philippines, 5000
    • GSK Investigational Site
  • Manila, Philippines, 1000
    • GSK Investigational Site
  • Marilao, Bulacan, Philippines, 3019
    • GSK Investigational Site
  • Pasig City, Philippines, 1600
    • GSK Investigational Site
  • Quezon City, Philippines, 1100
    • GSK Investigational Site
• Thailand
  • Bangkok, Thailand, 10400
    • GSK Investigational Site
  • Bangkok, Thailand, 10700
    • GSK Investigational Site
  • Chiangmai, Thailand, 50200
    • GSK Investigational Site
  • Khon Kaen, Thailand, 40002
    • GSK Investigational Site
  • Muang, Thailand, 11000
    • GSK Investigational Site
  • Muang, Thailand, 65000
    • GSK Investigational Site
  • Nan, Thailand, 55000
    • GSK Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • GSK Investigational Site
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • GSK Investigational Site
  • California
    • Newport Beach, California, United States, 92663
      • GSK Investigational Site
    • Torrance, California, United States, 90505
      • GSK Investigational Site
  • Florida
    • DeLand, Florida, United States, 32720
      • GSK Investigational Site
    • Gainesville, Florida, United States, 32608
      • GSK Investigational Site
    • Orlando, Florida, United States, 32825
      • GSK Investigational Site
    • Ormond Beach, Florida, United States, 32174
      • GSK Investigational Site
    • Winter Park, Florida, United States, 32789
      • GSK Investigational Site
  • Georgia
    • Duluth, Georgia, United States, 30096
      • GSK Investigational Site
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • GSK Investigational Site
  • Indiana
    • Avon, Indiana, United States, 46123
      • GSK Investigational Site
    • Lafayette, Indiana, United States, 47904
      • GSK Investigational Site
    • Muncie, Indiana, United States, 47304-5547
      • GSK Investigational Site
  • Kansas
    • Topeka, Kansas, United States, 66606
      • GSK Investigational Site
  • Michigan
    • Traverse City, Michigan, United States, 49684
      • GSK Investigational Site
  • Missouri
    • Saint Charles, Missouri, United States, 63301
      • GSK Investigational Site
    • Saint Louis, Missouri, United States, 63141
      • GSK Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • GSK Investigational Site
    • Shelby, North Carolina, United States, 28152
      • GSK Investigational Site
    • Winston-Salem, North Carolina, United States, 27103
      • GSK Investigational Site
  • Ohio
    • Columbus, Ohio, United States, 43215
      • GSK Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • GSK Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • GSK Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • GSK Investigational Site
  • South Carolina
    • Easley, South Carolina, United States, 29640
      • GSK Investigational Site
    • Fort Mill, South Carolina, United States, 29707
      • GSK Investigational Site
    • Gaffney, South Carolina, United States, 29340
      • GSK Investigational Site
    • Greenville, South Carolina, United States, 29615
      • GSK Investigational Site
    • 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
    • Union, South Carolina, United States, 29379
      • GSK Investigational Site
  • Tennessee
    • Johnson City, Tennessee, United States, 37601
      • GSK Investigational Site
  • Texas
    • Edinburg, Texas, United States, 78539
      • GSK Investigational Site
  • Virginia
    • Abingdon, Virginia, United States, 24210
      • 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:

• COPD diagnosis defined by ATS/ERS
• Former or current smoker
• A measured aortic pulse wave velocity = or > 11.0 m/s at Screening

Exclusion Criteria:

• Pregnancy
• A current diagnosis of asthma
• alpha1-antitrypsin deficiency as the underlying cause of COPD
• subjects with other and active respiratory disorders
• A cardiovascular event occurred in the 6 months prior to Visit 1
• Current severe heart failure (New York Heart Association Class IV) and have a known ejection fraction of < 30 %
• Clinical significant and uncontrolled hypertension
• Abnormal and clinical significant 12-lead ECG findings at Visit 1
• Have lung volume reduction or lung transplantation within 12 months prior to Visit 1
• Poorly controlled COPD: Acute worsening of COPD that is managed by subject with antibiotics or corticosteroids, or requires treatment prescribed by a physician in the 6 weeks prior to Visit 1; or subject needs to be hospitalised due to poorly controlled COPD within 12 weeks prior to Visit 1
• Lower respiratory tract infection that required use of antibiotics within 6 weeks prior to Visit 1
• Participate in the acute phase of a pulmonary rehabilitation within 4 weeks prior to Visit 1 or who will enter the acute phase of pulmonary rehabilitation during the study.
• Other diseases or abnormalities in the opinion of the investigator would put safety of the subject at risk through participation; or would affect the safety or efficacy analysis if the disease/condition exacerbated during the study.
• subjects with carcinoma has not been in complete remission for at least 5 years. Carcinoma in site of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded if the subject has been considered cured within 5 years since diagnosis.
• subjects with a history of hypersensitivity to any of the study medications or components of the inhalation powder.
• subjects with a known or suspected history of alcohol or drug abuse within the last 2 years prior to Screening
• subjects are medically unable to withhold albuterol or ipratropium for 4 hours prior to spirometry testing at each study visit
• subjects are medically unable to stop the 'excluded medications' listed in the protocol
• subjects started, discontinued certain medications listed in the protocol or have not been on a stable dose in the past three months prior to Screening, or are not anticipated to remain on a stable dose during the study treatment period.
• Long term oxygen therapy requiring >12 hour per day or a flow rate > 2 L/min
• A body mass index = or >35 kg/m2
• Fasting lipid level LDL>3.3 mmol/L, total cholesterol >5.2 mmol/L, and triglycerides > 2.24mmol/L
• Non-compliance
• Questionable validity of consent
• Prior use of study medication or other investigational drugs.
• 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluticasone Furoate/Vilanterol; Inhaled corticosteroid/long acting beta-agonist	Drug: Fluticasone Furoate/Vilanterol; Inhaled corticosteroid/long acting beta-agonist
Experimental: vilanterol; Inhaled long acting beta-agonist	Drug: Vilanterol; Inhaled long acting beta-agonist
Placebo Comparator: placebo; Placebo	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline (BL) in Aortic Pulse Wave Velocity (aPWV) at the End of the 24-week Treatment Period (Day 168)	PWV is defined as the speed of travel of the pressure pulse along an arterial segment and can be obtained for any arterial segment accessible to palpation. aPWV is measured with tonometers positioned transcutaneously at the base of the common carotid artery and over the femoral artery. PWV increases with arterial stiffness and is defined by the Moens-Korteweg equation: PWV=square root of (Eh/2ρR), where E is Young's modulus of the arterial wall, h is the wall thickness, R is the arterial radius at the end of diastole, and ρ is the blood density. Change from BL was calculated as the Day 168 value minus the BL value. The analysis was performed using a repeated measures model with covariates of treatment, visit, age, gender, smoking history, history of exacerbation strata, geographical region, BL aPWV and interaction terms of BL by visit and treatment by visit.	BL to Day 168

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From BL in Clinic Visit Trough (Pre-bronchodilator and Pre-dose) FEV1 at Day 168	Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Trough FEV1 measurements were taken electronically by spirometry at Screening, Days 1, 28, 84, 126, and 168. BL FEV1 was defined as the mean of the assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. Trough FEV1 was defined as the mean of the FEV1 values obtained 24 hours after previous morning's dosing. Change from BL was calculated as the average at each visit minus the BL value. Analysis was preformed using a repeated measures model with covariates of visit, treatment, history of exacerbation strata, geographical region, BL FEV1 and interaction terms of BL by visit and treatment by visit.	BL to Day 168
Mean Number of Occasions Rescue Medication [Albuterol (Salbutamol)] Used During a 24-hour Period Averaged Over the Entire 24-week Treatment Period	Participants were given daily record cards for daily completion from BL (Week -1) through Week 24 (Visit 6) each morning and prior to taking study medication (i.e., single-blind and double-blind study medication) supplemental medication (albuterol [salbutamol] if received) and ipratropium bromide (if received). Participants recorded number of occasions supplemental albuterol/salbutamol (MDI and/or nebules) used over the previous 24 hours and any medical problems that they had experienced and any medication used to treat these medical problems over the previous 24 hours. Analysis was performed using an analysis of covarience (ANCOVA) model with covariates of treatment, BL mean of occasions of rescue medication use (Week -1), history of exacerbation, and geographical region.	BL (Week -1), Week 1 to Week 24

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 (Actual): March 4, 2011
• Primary Completion (Actual): November 4, 2014
• Study Completion (Actual): November 4, 2014

Study Registration Dates

• First Submitted: March 31, 2011
• First Submitted That Met QC Criteria: April 14, 2011
• First Posted (Estimate): April 18, 2011

Study Record Updates

• Last Update Posted (Actual): November 8, 2017
• Last Update Submitted That Met QC Criteria: October 9, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Fluticasone; Xhance
• Other Study ID Numbers: 113108

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. Individual Participant Data Set
   Information identifier: 113108
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: 113108
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: 113108
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 113108
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: 113108
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 113108
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Clinical Study Report
   Information identifier: 113108
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register