A Study to Compare the Impact of Fulticasone Furoate/Vilanterol vs. Tiotropium on Arterial Stiffness in COPD

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

A 12 Week Study to Evaluate the Effect of Fluticasone Furoate (FF, GW685698)/Vilanterol (VI, GW642444) 100/25 mcg Inhalation Powder Delivered Once Daily Via a Novel Dry Powder Inhaler (NDPI) on Arterial Stiffness Compared With Tiotropium Bromide 18 mcg Delivered Once Daily Via a HandiHaler in Subjects With Chronic Obstructive Pulmonary Disease (COPD).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01395888
• Other study ID #: 115247
• Status: Completed
• Phase: Phase 3
• First received: July 14, 2011
• Last updated: January 18, 2018
• Start date: June 30, 2011
• Est. completion date: August 6, 2012

Study information

• Verified date: January 2018
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to evaluate the effect of fluticasone furoate (FF, GW685698)/vilanterol (VI, GW642444) Inhalation Powder once daily (QD) on arterial stiffness compared with Tiotropium QD over 12 week treatment period in subjects with COPD and aortic pulse wave velocity (aPWV) > 12.0 m/s at Visit 1. Arterial stiffness will be measured as aPWV. This is a comparator, randomised, double-blind, double-dummy, parallel group, multi-centre 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 an approximate 7-day Follow-up period after the treatment period.

Description:

This is a Phase IIIb comparator, double-blind, double-dummy, randomised (1:1), parallel group, multi-centre study. At Visit 1 (Screening Visit), subjects who meet the pre-defined Inclusion Criteria and none of the Exclusion Criteria will enter a 2-week, single-blind placebo Run-in Period. The purpose of the Run-In Period is to monitor albuterol/salbutamol use at baseline, and to ensure that subjects' COPD is at a stable stage at randomization. Subject's adherence with study procedures, diary completion will also be evaluated during the Run-In Period. At the end of the Run-in period, subjects will be assessed and those who meet the randomisation criteria will receive one of the following two double-blind treatments for 12 weeks:

• FF (100 mcg)/VI (25 mcg) administered QD via a NDPI in the morning

• Tiotropium (18 mcg) administered QD via a HandiHaler in the morning

To ensure blinding of the treatments and to ensure a double-dummy design matching NDPI and HandiHaler will be utilised. Each subject will be instructed to self administer blinded study drug during the double blind treatment period as follows:

• Each morning take 1 inhalation from NDPI containing FF (100 mcg)/VI (25 mcg) followed by 1 inhalation from placebo capsule delivered via HandiHaler.

• Each morning take 1 inhalation from matching placebo NDPI followed by 1 inhalation from a capsule containing tiotropium 18 mcg delivered via HandiHaler.

An inhaled short acting beta2-receptor agonist, salbutamol/albuterol will be provided to subjects to use as needed throughout the Run-in and Treatment periods for relief of COPD symptoms. Ipratropium bromide is permitted if the subject is on a stable dose from Screening (Visit 1) and remains on the stable dose throughout the study. Subjects who experience an exacerbation of their COPD (which requires medication in addition to an increase in rescue medication) or a lower respiratory tract infection (LRTI) during the run-in period are not eligible to enter the treatment period. Any subject who experiences a similar COPD exacerbation (sec 4.4) or LRTI at any time on therapy will be withdrawn from the study. The aPWV will be measured at Screening and clinic Visits 3-5. Disease specific health status will be evaluated using the St. George's Respiratory Questionnaire (SGRQ-C), Euro Qol Questionnaire (EQ-5D) for COPD patients and the COPD Assessment Test (CAT) at Visit 2 (Day 1) and at Visit 5 (Weeks 12). The 12-lead ECG will be evaluated at Visit 1 (Screening) only. Vital signs (blood pressure and pulse rate), spirometry measurements, and clinical laboratory tests (hematology and chemistry) and other study-specific safety assessments will be obtained at selected clinic visits. A follow-up phone call will occur approximately 7 days after the last clinic visit. The overall study duration from Screening to Follow-up for each subject is approximately 15 weeks. Subjects will be considered to have completed the study upon completion of assessments and procedures up to and including completion of Follow-up Phone Contact (7 ± 2 days post Visit 5).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 260
• Est. completion date: August 6, 2012
• Est. primary completion date: August 1, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• Type of subject: Outpatient

• Informed consent: Subjects must give their signed and dated written informed consent to participate.

• Gender: Male or female subjects.

• Age: greater then or equal to 40 years of age at Screening (Visit 1)

• COPD diagnosis: Subjects with a clinical history of COPD in accordance with the following definition by the American Thoracic Society (ATS) /European Respiratory Society(ERS).

• Subjects with a current or prior history ofgreater then or equal to 10 pack-years of cigarette smoking at Screening (Visit 1).

• Subjects with a measured post-albuterol/salbutamol FEV1 less then 70% of predicted at Screening (Visit 1).

• Subjects with a measured post-albuterol/salbutamol FEV1/FVC ratio of less then or equal to 0.70 at Screening (Visit 1).

• Exacerbation History: Subjects who have been hospitalised or have been treated with oral corticosteroids or antibiotics for their COPD within the last 3 years prior to Screening (V1).

• Baseline aPWV: subjects with a measured aPWV greater then 12.0 m/s at Screening (Visit 1).

Exclusion Criteria:

• Body Mass Index of less then or equal to 35

Related Conditions & MeSH terms

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

Intervention

Drug:
• fluticasone furoate (FF, GW685698)/vilanterol (VI, GW642444) 100/25 mcg Novel Dry Powder Inhaler (NDPI)
fluticasone furoate (FF, GW685698)/vilanterol (VI, GW642444) 100/25 mcg Inhalation Powder delivered once daily via a Novel Dry Powder Inhaler (NDPI)
• Tiotropium
• Tiotropium (18 mcg) administered QD via a HandiHaler

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	San Juan
Argentina	GSK Investigational Site	Tucuman
Argentina	GSK Investigational Site	Tucumán
France	GSK Investigational Site	Bethune Cedex
France	GSK Investigational Site	Grenoble Cedex 09
France	GSK Investigational Site	Lille
France	GSK Investigational Site	Montpellier cedex 5
France	GSK Investigational Site	Reims Cedex
France	GSK Investigational Site	Saint-Michel
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Geesthacht	Schleswig-Holstein
Germany	GSK Investigational Site	Goch	Nordrhein-Westfalen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Immenhausen	Hessen
Germany	GSK Investigational Site	Magdeburg	Sachsen-Anhalt
Germany	GSK Investigational Site	Schwerin	Mecklenburg-Vorpommern
Italy	GSK Investigational Site	Bologna	Emilia-Romagna
Italy	GSK Investigational Site	Cassano Murge (BA)	Puglia
Italy	GSK Investigational Site	Crema	Lombardia
Italy	GSK Investigational Site	Eboli (SA)	Campania
Italy	GSK Investigational Site	Pavia	Lombardia
Norway	GSK Investigational Site	Bergen
Norway	GSK Investigational Site	Bergen
Norway	GSK Investigational Site	Drammen
Norway	GSK Investigational Site	Fredrikstad
Norway	GSK Investigational Site	Skedsmokorset
Russian Federation	GSK Investigational Site	Chita
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Kokhma
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Penza
Russian Federation	GSK Investigational Site	Saratov
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	Vladivostok, Primorskiy Kray
Russian Federation	GSK Investigational Site	Voronezh
Russian Federation	GSK Investigational Site	Yaroslavl
Russian Federation	GSK Investigational Site	Yaroslavl
Ukraine	GSK Investigational Site	Cherkassy
Ukraine	GSK Investigational Site	Donetsk
Ukraine	GSK Investigational Site	Kharkiv
Ukraine	GSK Investigational Site	Kiev
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Yalta

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Argentina,  France,  Germany,  Italy,  Norway,  Russian Federation,  Ukraine, 

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 12-week Treatment Period (Day 84)	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/2pR, 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 p is the blood density. Change from Baseline was calculated as the Day 84 value minus the Baseline value. The analysis was performed using a repeated measures model with covariates of treatment, visit, age, gender, smoking status at screening, geographical region, Baseline aPWV, and interaction terms of Baseline by visit and treatment by visit.	Baseline to Day 84 (Early Withdrawal)

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