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

NCT01328444 | Completed Phase 3 Results

• 1 other identifier: 114417
• Study Type: interventional
• Target: 349
• Locations: 6 countries
• Sites: 31

Brief Summary

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)

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (2)

• 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.

  Week 12 of each treatment period (up to Study Week 29)

• 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.

  Week 12 of each treatment period (up to Study Week 29)

Secondary Outcomes (4)

• Change From Baseline in Inspiratory Capacity (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period

  Week 12 of each treatment period (up to Study Week 29)

• Change From Baseline in Functional Residual Capacity (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period

  Week 12 of each treatment period (up to Study Week 29)

• Change From Baseline in Residual Volume (Trough and 3-hours Post-dose) at Week 12 of Each Treatment Period

  Week 12 of each treatment period (up to Study Week 29)

• Change From Baseline in 3-hours Post-dose FEV1 at Week 12 of Each Treatment Period

  Week 12 of each treatment period (up to Study Week 29)

Study Arms (6)

GSK 573719 + GW642444 125/25

EXPERIMENTAL

125mcg/25mcg nDPI

Drug: GSK573719 + GW642444 62.5/25; Drug: GSK 573719 125; Drug: GW642444 25; Drug: Plb

GSK 573719 +GW642444 62.5/25

EXPERIMENTAL

62.5mcg/25mcg nDPI

Drug: GSK 573719 +GW642444 125/25; Drug: GSK 573719 62.5; Drug: GW642444 25; Drug: Plb

GSK 573719 125

EXPERIMENTAL

125mcg nDPI

Drug: GSK 573719 +GW642444 125/25; Drug: Plb

GSK 573719 62.5

EXPERIMENTAL

62.5 mcg nDPI

Drug: GSK573719 + GW642444 62.5/25; Drug: GW642444 25; Drug: Plb

GW 642444 25

EXPERIMENTAL

25mcg nDPI

Drug: GSK 573719 +GW642444 125/25; Drug: GSK573719 + GW642444 62.5/25; Drug: Plb

Plb

PLACEBO COMPARATOR

Plb nDPI

Drug: GSK 573719 +GW642444 125/25; Drug: GSK573719 + GW642444 62.5/25; Drug: GSK 573719 125; Drug: GSK 573719 62.5

Interventions

GSK 573719 +GW642444 125/25 DRUG

125mcg/ 25mcg

Also known as: High Dose Dual

GSK 573719 +GW642444 62.5/25; GSK 573719 125; GW 642444 25; Plb

GSK573719 + GW642444 62.5/25 DRUG

62.5mcg/25mcg

Also known as: Low Dose Dual

GSK 573719 + GW642444 125/25; GSK 573719 62.5; GW 642444 25; Plb

GSK 573719 125 DRUG

125mcg

Also known as: High Dose 719

GSK 573719 + GW642444 125/25; Plb

GSK 573719 62.5 DRUG

62.5mcg

Also known as: Low Dose 719

GSK 573719 +GW642444 62.5/25; Plb

GW642444 25 DRUG

25mcg

Also known as: LABA (444)

GSK 573719 + GW642444 125/25; GSK 573719 +GW642444 62.5/25; GSK 573719 62.5

Plb DRUG

Comparator

Also known as: Placebo

GSK 573719 + GW642444 125/25; GSK 573719 +GW642444 62.5/25; GSK 573719 125; GSK 573719 62.5; GW 642444 25

Eligibility Criteria

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

You may qualify if:

• 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
• 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.

You may not qualify if:

• Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
• Asthma: A current diagnosis of asthma.
• 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.
• 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).
• 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.
• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (31)

GSK Investigational Site

Phoenix, Arizona, 85006, United States

Location

GSK Investigational Site

Lebanon, New Hampshire, 03756, United States

Location

GSK Investigational Site

Albany, New York, 12205, United States

Location

GSK Investigational Site

Columbus, Ohio, 43215, United States

Location

GSK Investigational Site

Medford, Oregon, 97504, United States

Location

GSK Investigational Site

Gaffney, South Carolina, 29340, United States

Location

GSK Investigational Site

Greenville, South Carolina, 29615, United States

Location

GSK Investigational Site

Spartanburg, South Carolina, 29303, United States

Location

GSK Investigational Site

Union, South Carolina, 29379, United States

Location

GSK Investigational Site

Kingwood, Texas, 77339, United States

Location

GSK Investigational Site

Richmond, Virginia, 23229, United States

Location

GSK Investigational Site

Plovdiv, 4000, Bulgaria

Location

GSK Investigational Site

Sofia, 1000, Bulgaria

Location

GSK Investigational Site

Tallinn, 13619, Estonia

Location

GSK Investigational Site

Tartu, 51014, Estonia

Location

GSK Investigational Site

Gelnhausen, Hesse, 63571, Germany

Location

GSK Investigational Site

Wiesbaden, Hesse, 65187, Germany

Location

GSK Investigational Site

Bochum, North Rhine-Westphalia, 44787, Germany

Location

GSK Investigational Site

Solingen, North Rhine-Westphalia, 42651, Germany

Location

GSK Investigational Site

Witten, North Rhine-Westphalia, 58452, Germany

Location

GSK Investigational Site

Großhansdorf, Schleswig-Holstein, 22927, Germany

Location

GSK Investigational Site

Berlin, 10117, Germany

Location

GSK Investigational Site

Berlin, 10787, Germany

Location

GSK Investigational Site

Hamburg, 20253, Germany

Location

GSK Investigational Site

Hamburg, 20354, Germany

Location

GSK Investigational Site

Barnaul, 656 045, Russia

Location

GSK Investigational Site

Chelyabinsk, 454106, Russia

Location

GSK Investigational Site

Moscow, 105 077, Russia

Location

GSK Investigational Site

Moscow, 127018, Russia

Location

GSK Investigational Site

Saint Petersburg, 197022, Russia

Location

GSK Investigational Site

Northwood, Middlesex, HA6 2RN, United Kingdom

Location

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

GSK573719; phospholamban

Condition Hierarchy (Ancestors)

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

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: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2011
• First Posted: April 4, 2011
• Study Start: March 1, 2011
• Primary Completion: June 1, 2012
• Study Completion: June 14, 2012
• Last Updated: October 11, 2017
• Results First Posted: February 10, 2014

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

GB (1); US (11); BU (2); ES (2); DE (10); RU (5)