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

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01336608
• Other study ID #: 113108
• Status: Completed
• Phase: Phase 3
• First received: March 31, 2011
• Last updated: October 9, 2017
• Start date: March 4, 2011
• Est. completion date: November 4, 2014

Study information

• Verified date: October 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 446
• Est. completion date: November 4, 2014
• Est. primary completion date: November 4, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Fluticasone Furoate/Vilanterol
Inhaled corticosteroid/long acting beta-agonist
• Vilanterol
Inhaled long acting beta-agonist
• Placebo
Placebo

Locations

Country	Name	City	State
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Elsterwerda	Brandenburg
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Geesthacht	Schleswig-Holstein
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Leipzg	Sachsen
Germany	GSK Investigational Site	Luebeck	Schleswig-Holstein
Germany	GSK Investigational Site	Magdeburg	Sachsen-Anhalt
Korea, Republic of	GSK Investigational Site	Ansan
Korea, Republic of	GSK Investigational Site	Gwangju
Korea, Republic of	GSK Investigational Site	Ilsanseo-gu, Goyang-si, Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Pusan
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Norway	GSK Investigational Site	Elverum
Norway	GSK Investigational Site	Kløfta
Norway	GSK Investigational Site	Moss
Norway	GSK Investigational Site	Stavanger
Philippines	GSK Investigational Site	Dagupan City
Philippines	GSK Investigational Site	Jaro, Iloilo City
Philippines	GSK Investigational Site	Manila
Philippines	GSK Investigational Site	Marilao, Bulacan
Philippines	GSK Investigational Site	Pasig City
Philippines	GSK Investigational Site	Quezon City
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Chiangmai
Thailand	GSK Investigational Site	Khon Kaen
Thailand	GSK Investigational Site	Muang
Thailand	GSK Investigational Site	Muang
Thailand	GSK Investigational Site	Nan
United States	GSK Investigational Site	Abingdon	Virginia
United States	GSK Investigational Site	Avon	Indiana
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Coeur d'Alene	Idaho
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	DeLand	Florida
United States	GSK Investigational Site	Duluth	Georgia
United States	GSK Investigational Site	Easley	South Carolina
United States	GSK Investigational Site	Edinburg	Texas
United States	GSK Investigational Site	Fort Mill	South Carolina
United States	GSK Investigational Site	Gaffney	South Carolina
United States	GSK Investigational Site	Gainesville	Florida
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Johnson City	Tennessee
United States	GSK Investigational Site	Lafayette	Indiana
United States	GSK Investigational Site	Medford	Oregon
United States	GSK Investigational Site	Muncie	Indiana
United States	GSK Investigational Site	Newport Beach	California
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Ormond Beach	Florida
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Rock Hill	South Carolina
United States	GSK Investigational Site	Saint Charles	Missouri
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	Seneca	South Carolina
United States	GSK Investigational Site	Shelby	North Carolina
United States	GSK Investigational Site	Spartanburg	South Carolina
United States	GSK Investigational Site	Topeka	Kansas
United States	GSK Investigational Site	Torrance	California
United States	GSK Investigational Site	Traverse City	Michigan
United States	GSK Investigational Site	Union	South Carolina
United States	GSK Investigational Site	Winston-Salem	North Carolina
United States	GSK Investigational Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Germany,  Korea, Republic of,  Norway,  Philippines,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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/2?R), 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 ? 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	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
Secondary	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

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