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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01395888
First received: July 14, 2011
Last updated: August 22, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: fluticasone furoate (FF, GW685698)/vilanterol (VI, GW642444) 100/25 mcg Novel Dry Powder Inhaler (NDPI)
Drug: Tiotropium
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A 12week 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).

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Mean Change From Baseline (BL) in Aortic Pulse Wave Velocity (aPWV) at the End of the 12-week Treatment Period (Day 84) [ Time Frame: Baseline to Day 84 (Early Withdrawal) ] [ Designated as safety issue: No ]
    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.


Enrollment: 260
Study Start Date: June 2011
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Relovair
Inhaled long-acting bronchodilator and corticosteroid combination
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)
Active Comparator: Tiotropium
Inhaled long-acting anticholinergic
Drug: Tiotropium
• Tiotropium (18 mcg) administered QD via a HandiHaler

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).

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01395888

  Hide Study Locations
Locations
Argentina
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1056ABJ
GSK Investigational Site
Rosario, Santa Fe, Argentina, S2000JKR
GSK Investigational Site
Buenos Aires, Argentina, C1425BEN
GSK Investigational Site
Buenos Aires, Argentina, C1424BSF
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, C1426ABO
GSK Investigational Site
Mendoza, Argentina, 5500
GSK Investigational Site
Mendoza, Argentina, M5500CCG
GSK Investigational Site
San Juan, Argentina, 5400
GSK Investigational Site
Tucuman, Argentina, 4000
GSK Investigational Site
Tucumán, Argentina, T4000DGF
France
GSK Investigational Site
Bethune Cedex, France, 62408
GSK Investigational Site
Grenoble Cedex 09, France, 38043
GSK Investigational Site
Lille, France, 59000
GSK Investigational Site
Montpellier cedex 5, France, 34295
GSK Investigational Site
Reims Cedex, France, 51092
GSK Investigational Site
Saint-Michel, France, 16470
Germany
GSK Investigational Site
Immenhausen, Hessen, Germany, 34376
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, Germany, 19055
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30159
GSK Investigational Site
Goch, Nordrhein-Westfalen, Germany, 47574
GSK Investigational Site
Magdeburg, Sachsen-Anhalt, Germany, 39112
GSK Investigational Site
Geesthacht, Schleswig-Holstein, Germany, 21502
GSK Investigational Site
Berlin, Germany, 13125
GSK Investigational Site
Berlin, Germany, 10787
GSK Investigational Site
Berlin, Germany, 10789
GSK Investigational Site
Hamburg, Germany, 20354
Italy
GSK Investigational Site
Eboli (SA), Campania, Italy, 84025
GSK Investigational Site
Bologna, Emilia-Romagna, Italy, 40138
GSK Investigational Site
Crema, Lombardia, Italy, 26013
GSK Investigational Site
Pavia, Lombardia, Italy, 27100
GSK Investigational Site
Cassano Murge (BA), Puglia, Italy, 70020
Norway
GSK Investigational Site
Bergen, Norway, N-5021
GSK Investigational Site
Bergen, Norway, 5017
GSK Investigational Site
Drammen, Norway, 3004
GSK Investigational Site
Fredrikstad, Norway, 1606
GSK Investigational Site
Skedsmokorset, Norway, N-2020
Russian Federation
GSK Investigational Site
Chita, Russian Federation, 672000
GSK Investigational Site
Kemerovo, Russian Federation, 650002
GSK Investigational Site
Kokhma, Russian Federation, 153511
GSK Investigational Site
Moscow, Russian Federation, 115093
GSK Investigational Site
Moscow, Russian Federation, 105077
GSK Investigational Site
Penza, Russian Federation, 440067
GSK Investigational Site
Saratov, Russian Federation, 410053
GSK Investigational Site
St. Petersburg, Russian Federation, 197022
GSK Investigational Site
Vladivostok, Primorskiy Kray, Russian Federation, 690022
GSK Investigational Site
Voronezh, Russian Federation, 394018
GSK Investigational Site
Yaroslavl, Russian Federation, 150003
GSK Investigational Site
Yaroslavl, Russian Federation, 150062
Ukraine
GSK Investigational Site
Cherkassy, Ukraine, 18009
GSK Investigational Site
Donetsk, Ukraine, 83099
GSK Investigational Site
Kharkiv, Ukraine, 61035
GSK Investigational Site
Kiev, Ukraine, 03680
GSK Investigational Site
Kyiv, Ukraine, 03680
GSK Investigational Site
Kyiv, Ukraine, 03049
GSK Investigational Site
Yalta, Ukraine, 98603
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01395888     History of Changes
Other Study ID Numbers: 115247
Study First Received: July 14, 2011
Results First Received: June 6, 2013
Last Updated: August 22, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Fluticasone
Tiotropium
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014