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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01336608
First received: March 31, 2011
Last updated: June 15, 2015
Last verified: April 2015
  Purpose
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.

Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: Fluticasone Furoate/Vilanterol
Drug: Vilanterol
Drug: Placebo
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 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).

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 24-week Treatment Period (Day 168) [ Time Frame: BL to Day 168 ] [ 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/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.


Secondary Outcome Measures:
  • Change From BL in Clinic Visit Trough (Pre-bronchodilator and Pre-dose) FEV1 at Day 168 [ Time Frame: BL to Day 168 ] [ Designated as safety issue: No ]
    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.

  • Mean Number of Occasions Rescue Medication [Albuterol (Salbutamol)] Used During a 24-hour Period Averaged Over the Entire 24-week Treatment Period [ Time Frame: BL (Week -1), Week 1 to Week 24 ] [ Designated as safety issue: No ]
    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.


Enrollment: 446
Study Start Date: March 2011
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01336608

  Show 72 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01336608     History of Changes
Other Study ID Numbers: 113108 
Study First Received: March 31, 2011
Results First Received: June 15, 2015
Last Updated: June 15, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Chronic Disease
Respiratory Tract Diseases
Lung Diseases, Obstructive
Disease Attributes
Pathologic Processes
Fluticasone
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents

ClinicalTrials.gov processed this record on September 26, 2016