A Study to Assess the Efficacy of Fluticasone Furoate/Vilanterol (FF/VI) Inhalation Powder 100/25 mcg Once Daily Compared With Fluticasone Propionate/Salmeterol Inhalation Powder 250/50 mcg Twice Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

NCT01706328 | Completed Phase 3 Results

• 1 other identifier: 116974
• Study Type: interventional
• Target: 828
• Locations: 5 countries
• Sites: 63

Brief Summary

This will be a Phase IIIb multicentre, randomized, double-blind, double-dummy, 12-week parallel group study evaluating the effects of once daily in the morning treatment of FF/VI Inhalation Powder versus Fluticasone Propionate/Salmeterol Inhalation Powder twice daily on lung function in COPD subjects. Subjects will be screened and will enter a 2-week, single-blind (placebo), Run-In Period to evaluate the subject's adherence with study treatment, study procedures and assessment of disease stability. At the end of the Run-In Period, subjects will return to the Clinic and who meet all of the Randomization Criteria will be randomized to double-blind study medication (12-week treatment period). Subjects will be randomized to receive either FF/VI 100/25 via NDPI or Fluticasone Propionate/Salmeterol 250/50mcg via ACCUHALER/DISKUS. Matching placebos will be available in NDPI and ACCUHALER/DISKUS. Each morning (approximately 6-10 AM) subjects will take 1 inhalation from the NDPI followed by 1 inhalation from the ACCUHALER/DISKUS. Each evening (approximately 6-10 PM), approximately 12 hours after the morning dose with blinded study medication, subjects will take 1 inhalation from the ACCUHALER/DISKUS. Subjects will return to the clinic at the end of the treatment period. A follow-up phone contact will be performed approximately 7 days after the last clinic visit. The overall study duration (Screening to Follow-up) for each subject is approximately 15 weeks.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Vilanterol (VI); Novel Dry Powder Inhaler (NDPI); FEV1; Fluticasone Furoate (FF); COPD

Outcome Measures

Primary Outcomes (1)

• Change From Baseline Trough in Weighted-mean 24-hour Serial Forced Expiratory Volume in One Second (FEV1) on Treatment Day 84

  FEV1 is a measure of lung function and is defined as the volume of air that can be forcefully exhaled in one second. The weighted mean was calculated from the pre-dose FEV1 and the post-dose FEV1 measurements taken at 5, 15, 30, and 60 minutes and 2, 4, 6, 8, 12, 13, 14, 16, 20, and 24 hours on Treatment Day 84. Baseline trough FEV1 was calculated as the mean of the two assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. The weighted mean was derived by calculating the area under curve, and then dividing by the relevant time interval. The weighted mean change from Baseline was calculated as the weighted mean of the 24-hour serial FEV1 measurements on Day 84 minus the Baseline trough FEV1 value. The analysis used an analysis of covariance (ANCOVA) model with covariates of Baseline FEV1, reversibility stratum, smoking status (at Screening), country, and treatment.

  Baseline and Day 84

Secondary Outcomes (2)

• Time to Onset on Treatment Day 1

  Baseline and Day 1

• Change From Baseline in Trough FEV1 on Treatment Day 85

  Baseline and Day 85

Study Arms (2)

FF/VI Inhalation Powder NDPI

EXPERIMENTAL

Subjects randomized to the FF/VI 100/25 arm will take an active inhalation of study medication during their morning dosing from their NDPI and will have an inhalation of dummy medication (placebo) as their morning ACCUHALER/DISKUS dose and as their evening dose.

Drug: FF/VI 100/25 Inhalation Powder NDPI; Drug: Placebo Inhalation Powder ACCUHALER/DISKUS; Drug: Salbutamol as needed

Fluticasone Propionate/Salmeterol Inhalation Powder

ACTIVE COMPARATOR

Subjects randomized to the Fluticasone Propionate/Salmeterol Inhalation Powder 250/50mcg arm will have an active dose of medication during both their morning and evening treatments from the ACCUHALER/DISKUS and a dummy placebo dose in the morning from their NDPI.

Drug: Fluticasone Propionate/Salmeterol 250/50 Inhalation Powder ACCUHALER/DISKUS; Drug: Placebo Inhalation Powder NDPI; Drug: Salbutamol as needed

Interventions

FF/VI 100/25 Inhalation Powder NDPI DRUG

Subjects randomized to the FF/VI Inhalation Powder Novel Dry Powder Inhaler (NDPI) arm will receive a single inhalation of 100 mcg FF and 25 mcg VI via NDPI every morning for 12 weeks.

FF/VI Inhalation Powder NDPI

Fluticasone Propionate/Salmeterol 250/50 Inhalation Powder ACCUHALER/DISKUS DRUG

Subjects randomized to the Fluticasone Propionate/Salmeterol Inhalation Powder ACCUHALER/DISKUS arm will receive a single inhalation of 250 mcg Fluticasone Propionate and 50 mcg Salmeterol via ACCUHALER/DISKUS once in the morning and once in the evening for 12 weeks.

Also known as: ACCUHALER and DISKUS are registered trade marks of the GlaxoSmithKline Group of companies

Fluticasone Propionate/Salmeterol Inhalation Powder

Placebo Inhalation Powder NDPI DRUG

Subjects randomized to the Fluticasone Propionate/Salmeterol Inhalation Powder ACCUHALER/DISKUS arm will receive a single inhalation of placebo inhalation powder via NDPI every morning for 12 weeks.

Also known as: ACCUHALER and DISKUS are registered trade marks of the GlaxoSmithKline Group of companies

Fluticasone Propionate/Salmeterol Inhalation Powder

Placebo Inhalation Powder ACCUHALER/DISKUS DRUG

Subjects randomized to the FF/VI Inhalation Powder NDPI arm will receive a single inhalation of placebo inhalation powder via ACCUHALER/DISKUS once in the morning and once in the evening for 12 weeks.

FF/VI Inhalation Powder NDPI

Salbutamol as needed DRUG

Salbutamol inhalation powder

FF/VI Inhalation Powder NDPI; Fluticasone Propionate/Salmeterol Inhalation Powder

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A male or female \>=40 years of age at Screening (Visit 1).
• Capable of giving written informed consent.
• Female subjects must be post-menopausal or using a highly effective method for avoidance of pregnancy.
• Subjects with a clinical history of COPD in accordance with the following definition by the American Thoracic Society/European Respiratory Society.
• Subject with a measured post-albuterol (salbutamol) FEV1/forced vital capacity(FVC) ratio of \<=0.70 at Screening.
• Subjects with a measured post-albuterol (salbutamol) FEV1 \<=70% of predicted normal values.
• Subjects with a current or prior history of ≥10 pack-years of cigarette smoking at Screening.

You may not qualify if:

• Current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD).
• Other respiratory disorders (alpha1-antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, pulmonary fibrosis, pulmonary hypertension, interstitial lung diseases, or other active pulmonary diseases).
• Lung volume reduction surgery within the 12 months prior to Screening.
• Hospitalized due to poorly controlled COPD within 12 weeks of Screening.
• Poorly controlled COPD (occurrence of the following in the 6 weeks prior to Screening -Acute worsening of COPD that is managed by the subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician).
• Lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Screening.
• Moderate/severe COPD exacerbation/lower respiratory tract infection during Run-In Period.
• Abnormal and clinically significant 12-lead ECG at Screening
• Historical or current evidence of uncontrolled or clinically significant disease like cardiovascular, hypertension, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease), peptic ulcer disease, or haematological abnormalities. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
• History of hypersensitivity to any of the study medications or components of the inhalation powder; or history of severe milk protein allergy.
• Known or suspected history of alcohol or drug abuse within the last 2 years.
• Subjects who are medically unable to withhold their albuterol (salbutamol) and/or their ipratropium for the 4-hour period required prior to spirometry testing at each study visit.
• The subject has taken any other investigational drug within 30 days or 5 half-lives of the investigational product (IP) prior to the first dosing day in the current study.
• Use of additional medications prior to Screening (list of medications and time intervals are different for different class of medications and are indicated in the protocol)
• Subjects who have participated in the acute phase of a Pulmonary Rehabilitation Program within 4 weeks prior to Screening

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (63)

GSK Investigational Site

Clearwater, Florida, 33765, United States

Location

GSK Investigational Site

DeLand, Florida, 32720, United States

Location

GSK Investigational Site

Coeur d'Alene, Idaho, 83814, United States

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GSK Investigational Site

Normal, Illinois, 61761, United States

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GSK Investigational Site

Woodbury, Minnesota, 55125, United States

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GSK Investigational Site

Charlotte, North Carolina, 28207, United States

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GSK Investigational Site

Columbus, Ohio, 43215, United States

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GSK Investigational Site

Easley, South Carolina, 29640, United States

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GSK Investigational Site

Gaffney, South Carolina, 29340, United States

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GSK Investigational Site

Greenville, South Carolina, 29615, United States

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GSK Investigational Site

Orangeburg, South Carolina, 29118, United States

Location

GSK Investigational Site

Rock Hill, South Carolina, 29732, United States

Location

GSK Investigational Site

Seneca, South Carolina, 29678, United States

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GSK Investigational Site

Spartanburg, South Carolina, 29303, United States

Location

GSK Investigational Site

Union, South Carolina, 29379, United States

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GSK Investigational Site

Renton, Washington, 98055, United States

Location

GSK Investigational Site

Cottbus, Brandenburg, 03050, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60389, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

Location

GSK Investigational Site

Neu-Isenburg, Hesse, 63263, Germany

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GSK Investigational Site

Hanover, Lower Saxony, 30159, Germany

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GSK Investigational Site

Hanover, Lower Saxony, 30173, Germany

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GSK Investigational Site

Delitzsch, Saxony, 04509, Germany

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GSK Investigational Site

Dresden, Saxony, 01069, Germany

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GSK Investigational Site

Leipzg, Saxony, 04109, Germany

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GSK Investigational Site

Leipzig, Saxony, 04207, Germany

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GSK Investigational Site

Berlin, 10717, Germany

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GSK Investigational Site

Berlin, 10787, Germany

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GSK Investigational Site

Berlin, 12157, Germany

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GSK Investigational Site

Berlin, 12203, Germany

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GSK Investigational Site

Berlin, 13125, Germany

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GSK Investigational Site

Hamburg, 20253, Germany

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GSK Investigational Site

Bacau, 600114, Romania

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GSK Investigational Site

Brasov, 500118, Romania

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GSK Investigational Site

Brasov, 500283, Romania

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GSK Investigational Site

Brăila, 810003, Romania

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GSK Investigational Site

Bucharest, 030317, Romania

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GSK Investigational Site

Bucharest, 70000, Romania

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GSK Investigational Site

Cluj-Napoca, 400371, Romania

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GSK Investigational Site

Iași, 700115, Romania

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GSK Investigational Site

Piteşti, 110084, Romania

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GSK Investigational Site

Ploieşti, 100379, Romania

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GSK Investigational Site

Râmnicu Vâlcea, 240564, Romania

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GSK Investigational Site

Suceava, 720284, Romania

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GSK Investigational Site

Timișoara, 300310, Romania

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GSK Investigational Site

Chelyabinsk, 454106, Russia

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GSK Investigational Site

Kemerovo, 650000, Russia

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GSK Investigational Site

Kemerovo, 650002, Russia

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GSK Investigational Site

Kursk, 305035, Russia

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GSK Investigational Site

Novosibirsk, 630051, Russia

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GSK Investigational Site

Novosibirsk, 630102, Russia

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GSK Investigational Site

Perm, 614077, Russia

Location

GSK Investigational Site

Saint Petersburg, 194291, Russia

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GSK Investigational Site

Saint Petersburg, 194356, Russia

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GSK Investigational Site

Saint Petersburg, 195271, Russia

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GSK Investigational Site

Ulyanovsk, 432063, Russia

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GSK Investigational Site

Vladivostok, 690002, Russia

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GSK Investigational Site

Yaroslavl, 150003, Russia

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GSK Investigational Site

Kharkiv, 61035, Ukraine

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GSK Investigational Site

Kiev, 03680, Ukraine

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GSK Investigational Site

Kyiv, 03038, Ukraine

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GSK Investigational Site

Kyiv, 03680, Ukraine

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GSK Investigational Site

Kyiv, 04201, Ukraine

Location

Related Publications (1)

• Dransfield MT, Feldman G, Korenblat P, LaForce CF, Locantore N, Pistolesi M, Watkins ML, Crim C, Martinez FJ. Efficacy and safety of once-daily fluticasone furoate/vilanterol (100/25 mcg) versus twice-daily fluticasone propionate/salmeterol (250/50 mcg) in COPD patients. Respir Med. 2014 Aug;108(8):1171-9. doi: 10.1016/j.rmed.2014.05.008. Epub 2014 Jun 19.

  PMID: 24998880 DERIVED

Related Links

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

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Fluticasone; Albuterol; Health Services Needs and Demand

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Health Services Research; Health Planning; Health Care Economics and Organizations; Delivery of Health Care; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2012
• First Posted: October 15, 2012
• Study Start: October 15, 2012
• Primary Completion: June 17, 2013
• Study Completion: June 17, 2013
• Last Updated: May 2, 2018
• Results First Posted: March 5, 2014

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will share

Locations

US (16); RU (13); RO (13); UA (5); DE (16)