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

NCT ID: NCT01395888

Last Updated: 2018-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2012-08-06

Brief 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.

Detailed 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).

Conditions

Pulmonary Disease, Chronic Obstructive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Relovair

Inhaled long-acting bronchodilator and corticosteroid combination

Group Type: EXPERIMENTAL

fluticasone furoate (FF, GW685698)/vilanterol (VI, GW642444) 100/25 mcg Novel Dry Powder Inhaler (NDPI)

Intervention Type: DRUG

fluticasone furoate (FF, GW685698)/vilanterol (VI, GW642444) 100/25 mcg Inhalation Powder delivered once daily via a Novel Dry Powder Inhaler (NDPI)

Tiotropium

Inhaled long-acting anticholinergic

Group Type: ACTIVE_COMPARATOR

Tiotropium

Intervention Type: DRUG

• Tiotropium (18 mcg) administered QD via a HandiHaler

Interventions

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)

Intervention Type: DRUG

Tiotropium

• Tiotropium (18 mcg) administered QD via a HandiHaler

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Rosario, Santa Fe Province, Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Mendoza, , Argentina

GSK Investigational Site

Mendoza, , Argentina

GSK Investigational Site

San Juan, , Argentina

GSK Investigational Site

San Miguel de Tucumán, , Argentina

GSK Investigational Site

San Miguel de Tucumán, , Argentina

GSK Investigational Site

Béthune, , France

GSK Investigational Site

Grenoble, , France

GSK Investigational Site

Lille, , France

GSK Investigational Site

Montpellier, , France

GSK Investigational Site

Reims, , France

GSK Investigational Site

Saint-Michel, , France

GSK Investigational Site

Immenhausen, Hesse, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Schwerin, Mecklenburg-Vorpommern, Germany

GSK Investigational Site

Goch, North Rhine-Westphalia, Germany

GSK Investigational Site

Magdeburg, Saxony-Anhalt, Germany

GSK Investigational Site

Geesthacht, Schleswig-Holstein, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Cassano Murge (BA), Apulia, Italy

GSK Investigational Site

Eboli (SA), Campania, Italy

GSK Investigational Site

Bologna, Emilia-Romagna, Italy

GSK Investigational Site

Crema, Lombardy, Italy

GSK Investigational Site

Pavia, Lombardy, Italy

GSK Investigational Site

Bergen, , Norway

GSK Investigational Site

Bergen, , Norway

GSK Investigational Site

Drammen, , Norway

GSK Investigational Site

Fredrikstad, , Norway

GSK Investigational Site

Skedsmokorset, , Norway

GSK Investigational Site

Chita, , Russia

GSK Investigational Site

Kemerovo, , Russia

GSK Investigational Site

Kokhma, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Penza, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saratov, , Russia

GSK Investigational Site

Vladivostok, Primorskiy Kray, , Russia

GSK Investigational Site

Voronezh, , Russia

GSK Investigational Site

Yaroslavl, , Russia

GSK Investigational Site

Yaroslavl, , Russia

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, , Ukraine

Countries

Argentina; France; Germany; Italy; Norway; Russia; Ukraine

References

Pepin JL, Cockcroft JR, Midwinter D, Sharma S, Rubin DB, Andreas S. Long-acting bronchodilators and arterial stiffness in patients with COPD: a comparison of fluticasone furoate/vilanterol with tiotropium. Chest. 2014 Dec;146(6):1521-1530. doi: 10.1378/chest.13-2859.

Reference Type: DERIVED

PMID: 25058845 (View on PubMed)

Study Documents

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

115247

Identifier Type: -

Identifier Source: org_study_id