Pulmonary Disease, Chronic ObstructivePhase 3COPDNCT01323660

An Exercise Endurance Study to Evaluate the Effects of Treatment of Chronic Obstructive Pulmonary Disease (COPD) Patients With a Dual Bronchodilator: GSK573719/GW642444.Study B

A Phase 3 study testing GSK573719/GW642444 125/25, GSK573719/GW642444 62.5/25 and GSK573719 125 in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 53 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 40 years and older, men only
Conditions the study is for: Pulmonary Disease, Chronic Obstructive
What is being tested?: GSK573719/GW642444 125/25, GSK573719/GW642444 62.5/25 and GSK573719 125
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 307 participants
Where: 53 sitesin 7 countries
Study dates: 16 Mar 2011to 16 Jul 2012
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 years and older
Men only
No healthy volunteers
Adult, Older adult

Who may be able to join

Type of subject: Outpatient.
Informed Consent: A signed and dated written informed consent prior to study participation.
Age: 40 years of age or older at Visit 1.
Gender: Male or female subjects.
Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [Celli, 2004]
Smoking History: Current or former cigarette smokers with a history of cigarette smoking of ≥ 10 pack-years

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Severity of Disease: A post-albuterol/salbutamol FEV1/FVC ratio of 0.70 and a post-albuterol/salbutamol FEV1 of >35% and <70% of predicted normal
Dyspnea: A score of ≥2 on the Modified Medical Research Council Dyspnea Scale (mMRC) at Visit 1
Resting Lung Volumes: A resting FRC of ≥120% of predicted normal FRC at Visit 1.

Who cannot join

Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
Asthma: A current diagnosis of asthma.
Other Respiratory Disorders: Known respiratory disorders other than COPD including but not limited to alpha-1 antitrypsin deficiency, active tuberculosis, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, and interstitial lung disease. Allergic rhinitis is not exclusionary.
Other Diseases/Abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or haematological abnormalities that are uncontrolled and/or a previous history of cancer in remission for < 5 years prior to Visit 1 (localized carcinoma of the skin that has been resected for cure is not exclusionary). 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. Any physical or mental abnormality which would affect the patient carrying out exercise tests including peripheral vascular disease should be excluded at the investigators discretion.
Chest X-Ray: A chest X-ray or computed tomography (CT) scan that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. A chest X-ray must be taken at Visit 1 if a chest X-ray or CT scan is not available within 6 months prior to Visit 1. For subjects in Germany, if a chest X-ray (or CT scan) is not available in the 6 months prior to Visit 1 the subject will not be eligible for the study.
Contraindications: A history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the study physician contraindicates study participation or use of an inhaled anticholinergic.

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Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1).
12-Lead ECG: An abnormal and significant ECG finding from the 12-lead ECG conducted at Visit 1, including the presence of a paced rhythm on a 12-lead electrocardiogram (ECG) which causes the underlying rhythm and ECG to be obscured. Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility.
Screening Labs: Significantly abnormal finding from clinical chemistry and hematology tests at Visit 1.
Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
Medications prior to Screening, including depot,oral corticosteroids, combinations of LABA/ICS, LABA, PDE4 inhibitors.
Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day. As-needed oxygen use (i.e., <12 hours per day) is not exclusionary.
Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (e.g., albuterol/salbutamol) via nebulized therapy
Pulmonary Rehabilitation Program: Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.
Affiliation with Investigator Site: Is an investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study

Trial locations and contacts

53 sites in 7 countries.

Country

City, postcode or hospital

53 sites in 7 countries

United States18 sites

GSK Investigational Site
Albuquerque, New Mexico, 87108
GSK Investigational Site
Austell, Georgia, 30106
GSK Investigational Site
Austin, Texas, 78758
GSK Investigational Site
Brandon, Florida, 33511
GSK Investigational Site
Charleston, South Carolina, 29406-7108
GSK Investigational Site
Charlotte, North Carolina, 28207
GSK Investigational Site
Easley, South Carolina, 29640
GSK Investigational Site
Fort Collins, Colorado, 80528
GSK Investigational Site
Hartford, Connecticut, 06105
GSK Investigational Site
Jasper, Alabama, 35501
GSK Investigational Site
Lawrenceville, Georgia, 30046
GSK Investigational Site
Livonia, Michigan, 48152
GSK Investigational Site
Richmond, Virginia, 23225
GSK Investigational Site
Saint Charles, Missouri, 63301
GSK Investigational Site
St Louis, Missouri, 63141
GSK Investigational Site
The Woodlands, Texas, 77380
GSK Investigational Site
Topeka, Kansas, 66606
GSK Investigational Site
Torrance, California, 90505

Other trials in United States

United Kingdom9 sites

GSK Investigational Site
Birmingham, B9 5SS
GSK Investigational Site
Bradford, BD9 6RJ
GSK Investigational Site
Cottingham, East Yorkshire, HU16 5JQ
GSK Investigational Site
Doncaster, DN2 5LT
GSK Investigational Site
Glasgow, G11 6NT
GSK Investigational Site
Leicester, Leicestershire, LE3 9QP
GSK Investigational Site
Northwood, Middlesex, HA6 2RN
GSK Investigational Site
Somerset, TA1 5DA
GSK Investigational Site
Wolverhampton, WV10 00B

Other trials in United Kingdom

Czechia7 sites

GSK Investigational Site
Hradec Králové, 500 05
GSK Investigational Site
Karlovy Vary, 360 09
GSK Investigational Site
Ostrava - Poruba, 70868
GSK Investigational Site
Prague, 14059
GSK Investigational Site
Prague, 14800
GSK Investigational Site
Prague
GSK Investigational Site
Teplice, 415 10

Other trials in Czechia

South Africa6 sites

GSK Investigational Site
Bloemfontein, 9301
GSK Investigational Site
Gatesville, 7764
GSK Investigational Site
George, Eastern Cape, 6529
GSK Investigational Site
Groenkloof, 0181
GSK Investigational Site
Mowbray, 7700
GSK Investigational Site
Panorama, 7500

Other trials in South Africa

Canada5 sites

GSK Investigational Site
Hamilton, Ontario, L8N 3Z5
GSK Investigational Site
Montreal, Quebec, H2W 1T8
GSK Investigational Site
Québec, Quebec, G1V 4G5
GSK Investigational Site
Toronto, Ontario, M3H 5S4
GSK Investigational Site
Toronto, Ontario, M5T 3A9

Other trials in Canada

Denmark4 sites

GSK Investigational Site
Aarhus C, 8000
GSK Investigational Site
Hvidovre, 2650
GSK Investigational Site
København NV, 2400
GSK Investigational Site
Odense C, 5000

Other trials in Denmark

Ukraine4 sites

GSK Investigational Site
Donetsk, 83003
GSK Investigational Site
Kiev, 03680
GSK Investigational Site
Kyiv, 03038
GSK Investigational Site
Kyiv, 03115

Other trials in Ukraine

About this study

Official title: An Exercise Endurance Study to Evaluate the Effects of Treatment of Chronic Obstructive Pulmonary Disease (COPD) Patients With a Dual Bronchodilator: GSK573719/GW642444. Study B

Read the detailed description

Expiratory airflow limitation is the most obvious physiological change associated with chronic obstructive pulmonary disease (COPD). A consequence of airflow limitation is gas trapping as expiration becomes flow limited. This may occur at rest with more severe airway obstruction and is most evident during exercise as lung emptying is reduced and increased ventilation does not allow full expiration. This increased gas trapping or hyperinflation is the cause of much of the increased work of breathing, dyspnea, and exercise intolerance in subjects with COPD (O'Donnell 1997; O'Donnell, 1993). Spirometric measurement of airflow limitation, particularly as assessed by forced expiratory volume in one second (FEV1), is commonly used for the diagnosis of and assessment of response to pharmacotherapeutic intervention in COPD. However, changes in FEV1 may not fully predict symptomatic responses and alternative measures of lung hyperinflation such as exercise tolerance and exertional dyspnea may be more sensitive to therapeutic intervention and/or more clinically relevant than FEV1 [O'Donnell1999; Bauerle, 1998; O'Donnell, 1998; Officer, 1998]. GSK573719/GW642444 Inhalation Powder, a combination of the long-acting muscarinic antagonist (LAMA) bronchodilator GSK573719 and the long-acting beta2-agonist (LABA) bronchodilator GW642444, is in development for the maintenance treatment of airflow obstruction associated with COPD. Development of this product is supported by studies showing improvement in lung function with similar safety when use of combinations of long-acting bronchodilators with different mechanisms of action are compared with single bronchodilator therapy [van Noord 2005; van Noord van Noord 2006; Tashkin 2008]. Previous studies have demonstrated that treatment with short- and long-acting bronchodilators including ipratropium, tiotropium, and salmeterol reduces resting lung hyperinflation as measured by functional residual capacity (FRC), residual volume (RV), and inspiratory capacity (IC), with associated improvements in exercise endurance time and exertional dyspnoea in subjects with COPD [Ayers, 2001; O'Donnell 1998; O'Donnell 2004; Pepin 2005; Pepin 2007; Ramirez-Venegas 1997]. However, the effect of combined LAMA/LABA therapy on these measures is not well characterized.

This is a phase III multicenter, randomized, double-blind, placebo-controlled, combination and component, two-period, incomplete block design cross-over study using GSK573719/GW642444. The primary objective is to evaluate lung function and exercise endurance time after 12 weeks of once-daily administration of GSK573719/GW642444 Inhalation Powder (125/25mcg and 62.5/25mcg), GSK573719 Inhalation Powder (125mcg and 62.5mcg), GW642444 Inhalation Powder 25 mcg and placebo delivered by a Novel dry powder inhaler (Novel DPI) Approximately 312 subjects with moderate/severe chronic obstructive pulmonary disease (COPD) will be randomised in order to achieve 208 subjects completing both treatment periods of 3 months.. There will be a total of 12 study clinic visits conducted on an outpatient basis. Subjects who meet the eligibility criteria at Screening (Visit 1) will complete a 12 to 21 day run-in period followed by two 12-week treatment periods that are separated by a 14 day wash-out. Clinic visits will be conducted at Screening (Visit 1), twice during the run-in period (Visits 2 and 3), at randomization (Visit 4) and three times during the first treatment period, on Treatment Day 2 (Visit 5) and at 6 and 12 weeks (Visits 6 and 7 respectively). During the washout period of 14 days there will be 2 clinic visits (Visits 8 and 9). During the second treatment period there will be 3 clinic visits, on Treatment Day 2 (Visit 10) and at 6 and 12 weeks (Visits 11 and 12 respectively). A Safety Follow-Up assessment (Visit 13) to record adverse events will be conducted by telephone 7 days after the end of the second treatment period or early withdrawal. Efficacy measurements will include pre and post dose FEV1, lung volume measurements and exercise endurance time measured using the endurance shuttle walking test (ESWT). Safety and tolerability will be assessed by collection of adverse events (AEs), vital signs, 12-lead electrocardiograms (ECGs), clinical laboratory tests and incidence of COPD exacerbations. Dyspnea will be assessed using the Exercise Dyspnea Scale (EDS), a patient-reported outcome. Blood samples will also be collected for potential pharmacogenetics analysis

Conditions: Pulmonary Disease, Chronic Obstructive
Being tested: GSK573719/GW642444 125/25, GSK573719/GW642444 62.5/25, GSK573719 125, GSK573719 62.5, GW642444 25
Medical subject headings: Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK573719/GW642444 125/25Drug
125mcg/ 25mcg QID (Once daily , inhaled)
GSK573719/GW642444 62.5/25Drug
62.5mcg/25mcg QID
GSK573719 125Drug
125mcg QID
GSK573719 62.5Drug
62.5mcg QID
GW642444 25Drug
25mcg QID
placeboDevice
Comparator QID

Study groups in NCT01323660
Study group	Role	What they receive
GSK573719/GW642444 125/25	Experimental	125mcg/25mcg nDPI Receives: Drug: GSK573719 125; Drug: GW642444 25; Device: placebo
GSK573719/GW642444 62.5/25	Experimental	62.5mcg/25mcg nDPI Receives: Drug: GSK573719 62.5; Drug: GW642444 25; Device: placebo
GSK573719/ 125	Experimental	125mcg nDPI Receives: Drug: GSK573719/GW642444 125/25; Device: placebo
GSK573719 62.5	Experimental	62.5mcg nDPI Receives: Drug: GSK573719/GW642444 62.5/25; Device: placebo
GW642444 25	Experimental	25mcg nDPI Receives: Drug: GSK573719/GW642444 125/25; Drug: GSK573719/GW642444 62.5/25; Device: placebo
Placebo	Placebo comparator	Plb nDPI Receives: Drug: GSK573719/GW642444 125/25; Drug: GSK573719/GW642444 62.5/25; Drug: GSK573719 125; Drug: GSK573719 62.5; Drug: GW642444 25

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Exercise Endurance Time Post-dose at Week 12 of Each Treatment Period
Exercise endurance time (EET) post-dose at Week 12 is defined as the EET obtained 3 hours after dosing at Week 12. EET was measured using the externally paced field walking test called the endurance shuttle walk test (ESWT). Analysis performed using a repeated measures model with covariates of period walking speed, mean walking speed, period, treatment, visit, smoking status, center group, visit by period walking speed, visit by mean walking speed and visit by treatment interactions. The model used all available 3-hour post-dose change from baseline EET values recorded on Day 2, Week 6 and Week 12. Baseline was the EET assessment obtained prior to dosing on Day 1 of each period. The mean walking speed for each participant is the mean of the levels used for the ESWT in each of the two treatment periods. The period walking speed for each participant and treatment period is the difference between the level for that participant and period and the mean walking speed for that participant.
Measured: Week 12 of each treatment period (up to Study Week 30)
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 12 of Each Treatment Period
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 measurements were taken electronically by spirometry on Day 2, Week 6 and Week 12. Baseline is the FEV1 value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Clinic visit trough (pre-bronchodilator and pre-dose) FEV1 at Week 12 (Treatment Day 85) is defined as the FEV1 value obtained 24 hours after dosing on Treatment Day 84. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit, smoking status, center group, visit by period Baseline, visit by mean Baseline and visit by treatment interactions.
Measured: Week 12 of each treatment period (up to Study Week 30)

Secondary outcomes (4)

Change From Baseline in Inspiratory Capacity (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period
Inspiratory capacity (IC) is defined as the maximum amount of air that can be inhaled into the lungs from the normal resting position after breathing out normally. Baseline is the IC value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Trough IC is measured pre-dose on Treatment Week 12 of each treatment period. IC 3-hours post-dose is measured from the value obtained 3 hours after dosing on Treatment Week 12 of each treatment period. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit, smoking status, center group, visit by period Baseline, visit by mean Baseline and visit by treatment interactions. IC measurements were taken electronically by plethysmography on Day 2, Week 6 and Week 12.
Measured: Week 12 of each treatment period (up to Study Week 30)
Change From Baseline in Functional Residual Capacity (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period
Functional Residual Capacity (FRC) is defined as the amount of air still left in the lungs after breathing out normally. Baseline is the FRC value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Trough FRC is measured pre-dose on Treatment Week 12. FRC 3-hours post-dose is measured from the value obtained 3 hours after dosing on Treatment Week 12. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit, smoking status, center group, visit by period Baseline, visit by mean Baseline and visit by treatment interactions. FRC measurements were taken electronically by plethysmography on Day 2, Week 6 and Week 12.
Measured: Week 12 of each treatment period (up to Study Week 30)
Change From Baseline in Residual Volume (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period
Residual Volume (RV) is defined as the air that remains in the lungs after breathing out as fully as possible. Baseline is the RV value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Trough RV is measured pre-dose on Treatment Week 12. RV 3-hours post-dose is measured from the value obtained 3 hours after dosing on Treatment Week 12. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit, smoking status, center group, visit by period Baseline, visit by mean Baseline and visit by treatment interactions. RV measurements were taken electronically by plethysmography on Day 2, Week 6 and Week 1.
Measured: Week 12 of each treatment period (up to Study Week 30)
Change From Baseline in 3-hours Post-dose FEV1 at Week 12 of Each Treatment Period
FEVI is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Baseline is the FEV1 value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Clinic visit post-dose FEV1 at Week 12 (Treatment Day 85) is defined as the FEV1 value obtained 3 hours after dosing on Treatment Day 85. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit, smoking status, center group, visit by period Baseline, visit by mean Baseline and visit by treatment interactions 3 hour post-dose FEV1 measurements were taken electronically by spirometry on Day 2, Week 6 and Week 12.
Measured: Week 12 of each treatment period (up to Study Week 30)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Mar 201116 Jul 2012

First posted25 Mar 2011 (estimated)
Study start16 Mar 2011
Primary completion1 Jul 2012
Study completion16 Jul 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 307 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01323660
Sponsor's protocol ID: 114418
Acronym: COPD
Status last verified: Jan 2018
First submitted: 24 Mar 2011
Last updated: 15 Feb 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Pulmonary Disease, Chronic Obstructive trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Exercise Endurance Study to Evaluate the Effects of Treatment of Chronic Obstructive Pulmonary Disease (COPD) Patients With a Dual Bronchodilator: GSK573719/GW642444. Study B
ClinicalTrials.gov ID: NCT01323660
Acronym / sponsor ID: COPD / 114418
Conditions: Pulmonary Disease, Chronic Obstructive
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 307 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 16 Mar 2011
Primary completion: 1 Jul 2012 (actual)
Study completion: 16 Jul 2012 (actual)
First posted: 25 Mar 2011 (estimated)
Results: Posted 11 Apr 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 6

Arm	Type	Receives
GSK573719/GW642444 125/25	Experimental	Drug: GSK573719 125, Drug: GW642444 25, Device: placebo125mcg/25mcg nDPI
GSK573719/GW642444 62.5/25	Experimental	Drug: GSK573719 62.5, Drug: GW642444 25, Device: placebo62.5mcg/25mcg nDPI
GSK573719/ 125	Experimental	Drug: GSK573719/GW642444 125/25, Device: placebo125mcg nDPI
GSK573719 62.5	Experimental	Drug: GSK573719/GW642444 62.5/25, Device: placebo62.5mcg nDPI
GW642444 25	Experimental	Drug: GSK573719/GW642444 125/25, Drug: GSK573719/GW642444 62.5/25, Device: placebo25mcg nDPI
Placebo	Placebo comparator	Drug: GSK573719/GW642444 125/25, Drug: GSK573719/GW642444 62.5/25, Drug: GSK573719 125, Drug: GSK573719 62.5, Drug: GW642444 25Plb nDPI

Who may qualify

Ages: 40 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Type of subject: Outpatient.
Informed Consent: A signed and dated written informed consent prior to study participation.
Age: 40 years of age or older at Visit 1.
Gender: Male or female subjects.
Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [Celli, 2004]

Key exclusion criteria (17 listed)

Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
Asthma: A current diagnosis of asthma.
Other Respiratory Disorders: Known respiratory disorders other than COPD including but not limited to alpha-1 antitrypsin deficiency, active tuberculosis, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, and interstitial lung disease. Allergic rhinitis is not exclusionary.
Other Diseases/Abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or haematological abnormalities that are uncontrolled and/or a previous history of cancer in remission for < 5 years prior to Visit 1 (localized carcinoma of the skin that has been resected for cure is not exclusionary). 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. Any physical or mental abnormality which would affect the patient carrying out exercise tests including peripheral vascular disease should be excluded at the investigators discretion.
Chest X-Ray: A chest X-ray or computed tomography (CT) scan that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. A chest X-ray must be taken at Visit 1 if a chest X-ray or CT scan is not available within 6 months prior to Visit 1. For subjects in Germany, if a chest X-ray (or CT scan) is not available in the 6 months prior to Visit 1 the subject will not be eligible for the study.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK573719/GW642444 125/25125mcg/ 25mcg QID (Once daily , inhaled)	Drug	GSK573719/ 125, GW642444 25, Placebo
GSK573719/GW642444 62.5/2562.5mcg/25mcg QID	Drug	GSK573719 62.5, GW642444 25, Placebo
GSK573719 125125mcg QID	Drug	GSK573719/GW642444 125/25, Placebo
GSK573719 62.562.5mcg QID	Drug	GSK573719/GW642444 62.5/25, Placebo
GW642444 2525mcg QID	Drug	GSK573719/GW642444 125/25, GSK573719/GW642444 62.5/25, Placebo
placeboComparator QID	Device	GSK573719 62.5, GSK573719/ 125, GSK573719/GW642444 125/25, GSK573719/GW642444 62.5/25, GW642444 25

Primary outcome

Change From Baseline in Exercise Endurance Time Post-dose at Week 12 of Each Treatment Period
Time frame: Week 12 of each treatment period (up to Study Week 30)
Exercise endurance time (EET) post-dose at Week 12 is defined as the EET obtained 3 hours after dosing at Week 12. EET was measured using the externally paced field walking test called the endurance shuttle walk test (ESWT). Analysis performed using a repeated measures model with covariates of period walking speed, mean walking speed, period, treatment, visit, smoking status, center group, visit by period walking speed, visit by mean walking speed and visit by treatment interactions. The model used all available 3-hour post-dose change from baseline EET values recorded on Day 2, Week 6 and Week 12. Baseline was the EET assessment obtained prior to dosing on Day 1 of each period. The mean walking speed for each participant is the mean of the levels used for the ESWT in each of the two treatment periods. The period walking speed for each participant and treatment period is the difference between the level for that participant and period and the mean walking speed for that participant.
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 12 of Each Treatment Period
Time frame: Week 12 of each treatment period (up to Study Week 30)
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 measurements were taken electronically by spirometry on Day 2, Week 6 and Week 12. Baseline is the FEV1 value recorded pre-dose on Day 1 of each treatment period, mean Baseline is the mean of the Baselines for each participant, and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Clinic visit trough (pre-bronchodilator and pre-dose) FEV1 at Week 12 (Treatment Day 85) is defined as the FEV1 value obtained 24 hours after dosing on Treatment Day 84. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit, smoking status, center group, visit by period Baseline, visit by mean Baseline and visit by treatment interactions.

4 secondary outcomes

Change From Baseline in Inspiratory Capacity (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period
Time frame: Week 12 of each treatment period (up to Study Week 30)
Change From Baseline in Functional Residual Capacity (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period
Time frame: Week 12 of each treatment period (up to Study Week 30)
Change From Baseline in Residual Volume (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period
Time frame: Week 12 of each treatment period (up to Study Week 30)
Change From Baseline in 3-hours Post-dose FEV1 at Week 12 of Each Treatment Period
Time frame: Week 12 of each treatment period (up to Study Week 30)

Results and safety

Results posted to the registry on 11 Apr 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	84	65
UMEC 62.5 µg QD	22	21
UMEC 125 µg QD	24	19
VI 25 µg QD	36	31
UMEC/VI 62.5/25 µg QD	71	61
UMEC 125/25 µg QD	70	61

Primary outcome: Change From Baseline in Exercise Endurance Time Post-dose at Week 12 of Each Treatment Period

Time frame: Week 12 of each treatment period (up to Study Week 30). Least squares mean (Standard Error). Unit: Seconds

Measure	Placebo n = 117	UMEC 62.5 µg QD n = 37	UMEC 125 µg QD n = 32	VI 25 µg QD n = 54	UMEC/VI 62.5/25 µg QD n = 115	UMEC/VI 125/25 µg QD n = 109
Value	0.1 (16.66)	25.1 (30.18)	74.8 (31.58)	30.7 (24.79)	69.5 (17.09)	65.9 (17.48)

Placebo vs UMEC 62.5 µg QD: Least squares mean difference: 25.0 (95% CI -41.0 to 91.0), p = 0.456, Mixed Models Analysis
Placebo vs UMEC 125 µg QD: Least squares mean difference: 74.7 (95% CI 6.0 to 143.4), p = 0.033, Mixed Models Analysis
Placebo vs VI 25 µg QD: Least squares mean difference: 30.6 (95% CI -26.8 to 88.0), p = 0.295, Mixed Models Analysis

Population analysed: Intent-to-Treat (ITT) Population: all par. randomized to treatment who received at least one dose of study drug in either treatment period. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.

Primary outcome: Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 12 of Each Treatment Period

Time frame: Week 12 of each treatment period (up to Study Week 30). Least squares mean (Standard Error). Unit: Liters

Measure	Placebo n = 119	UMEC 62.5 µg QD n = 38	UMEC 125 µg QD n = 33	VI 25 µg QD n = 56	UMEC/VI 62.5/25 µg QD n = 117	UMEC/VI 125/25 µg QD n = 112
Value	-0.043 (0.0156)	0.101 (0.0267)	0.212 (0.0287)	0.069 (0.0222)	0.200 (0.0156)	0.218 (0.0159)

Placebo vs UMEC 62.5 µg QD: Least squares mean difference: 0.144 (95% CI 0.086 to 0.203), p <0.001, Mixed Models Analysis
Placebo vs UMEC 125 µg QD: Least squares mean difference: 0.255 (95% CI 0.193 to 0.318), p <0.001, Mixed Models Analysis
Placebo vs VI 25 µg QD: Least squares mean difference: 0.112 (95% CI 0.061 to 0.163), p <0.001, Mixed Models Analysis

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring while participants were on treatment up until one day after the last dose (up to Week 33), are reported.. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	4 of 151 (2.6%)	31 of 151 (20.5%)	Not reported
UMEC 62.5 µg QD	1 of 40 (2.5%)	5 of 40 (12.5%)	Not reported
UMEC 125 µg QD	1 of 41 (2.4%)	14 of 41 (34.1%)	Not reported
VI 25 µg QD	2 of 64 (3.1%)	12 of 64 (18.8%)	Not reported
UMEC/VI 62.5/25 µg QD	3 of 130 (2.3%)	20 of 130 (15.4%)	Not reported
UMEC/VI 125/25 µg QD	5 of 128 (3.9%)	18 of 128 (14.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

53 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in United States, United Kingdom, Czechia, South Africa, Canada and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Exercise Endurance Time Post-dose at Week 12 of Each Treatment Period (time frame: Week 12 of each treatment period (up to Study Week 30)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01323660.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2018.