A 52-Week, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Safety and Tolerability of GSK573719/GW642444 and GSK573719 in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (COPD nDPI)
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Purpose
The purpose of this 52-week study is to evaluate the long-term safety (in terms of adverse events, COPD exacerbations, laboratory, ECG, and Holter findings, vital signs, use of rescue medication and lung function) of GSK573719/GW642444 Inhalation Powder 125/25mcg in subjects with COPD. The long-term safety of GSK573719 Inhalation Powder 125mcg will also be evaluated. A placebo arm is included to evaluate these products compared to an inactive control.
| Condition | Intervention | Phase |
|---|---|---|
|
Pulmonary Disease, Chronic Obstructive |
Drug: 125/25 mcg once-daily Drug: 125mcg once-daily Drug: Placebo once-daily |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) |
| Official Title: | A 52 Week Study to Evaluate the Safety and Tolerability of GSK573719/GW642444 125mcg Once-daily Alone and in Combination With GW642444 25mcg Once-daily Via Novel Dry Powder Inhaler (nDPI) in Subjects With Chronic Obstructive Pulmonary Disease |
- incidence of adverse events [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]the occurrence of any adverse event during the 52 week treatment period
- incidence of COPD exacerbations [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]the incidence of any worsening symptoms of COPD treated with systemic corticosteroids, antibiotics, and/or resulted in hospitalization
- time to first COPD exacerbation [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]the time to the first occurrence of worsening symptoms of COPD treated with systemic corticosteroids, antibiotics, or hospitalization
- clinical laboratory tests [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]any effects on hematology or clinical chemistry tests
- vital signs [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]pulse rate and systolic and diastolic blood pressure
- 12 lead ECG assessments [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]heart rate, QTc(f), overall interpretation
- Holter reading assessments [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]24 hour cardiac monitoring-will measure important arrhythmias, overall interpretation
- Supplemental use of albuterol/salbutamol and/or ipratropium bromide [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]will measure via subject entries on daily paper diary cards the number of puffs and/or nebules taken from albuterol/salbutamol and/or ipratropium bromide
- Percentage of rescue-free days [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]Rescue free days refers to how many days albuterol/salbutamol and/or ipratropium bromide not used
- Trough forced expiratory volume in one second (FEV1) and forced vital capacity [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]measures of lung function-FEV1-how much air is expelled from the lungs in one second after a full inspiration and FVC-the total amount of air expelled from the lungs after a full inspiration
| Enrollment: | 563 |
| Study Start Date: | January 2011 |
| Study Completion Date: | July 2012 |
| Primary Completion Date: | July 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: GSK573719/GW642444
125/25 mcg once-daily
|
Drug: 125/25 mcg once-daily
GSK573719/GW642444
|
|
Experimental: GSK573719
125 mcg once-daily
|
Drug: 125mcg once-daily
GSK573719
|
|
Placebo Comparator: Placebo
inactive
|
Drug: Placebo once-daily
inactive
|
Detailed Description:
Several studies have demonstrated the efficacy and safety of combining an individual LABA compound plus an individual LAMA compound in COPD. These studies have shown the combination of these two products to be superior to either agent alone on a variety of outcomes in COPD. The beneficial effects of this combination regimen are likely due to the different mechanisms of action of the two bronchodilators (smooth bronchial muscle relaxation from activation of beta2 receptors from the LABA product and inhibition of acetylcholine-mediated smooth bronchial muscle contraction via blockade of muscarinic receptors from the LAMA product). The availability of a LABA/LAMA combination in one product instead of two individual products is a technical and therapeutic advancement in the pharmacological armamentarium for COPD and may lead to increased patient compliance due to once-daily administration. The purpose of this 52-week study is to evaluate the long-term safety (in terms of adverse events, COPD exacerbations, laboratory, ECG, and Holter findings, vital signs, use of rescue medication, and lung function) of GSK573719/GW642444 Inhalation Powder 125/25mcg in subjects with COPD. The long-term safety of GSK573719 Inhalation Powder 125mcg will also be evaluated. A placebo arm is included to evaluate these products compared to an inactive control. All treatments will be delivered once-daily via the nDPI. This study will establish the long-term safety profile of GSK573719/GW642444 Inhalation Powder 125/25mcg once-daily in subjects with COPD. The safety profile of GSK573719 Inhalation Powder125mcg once-daily will also be evaluated.
Eligibility| Ages Eligible for Study: | 40 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- outpatient
- signed and dated written informed consent
- 40 years of age or older
- male and female subjects
- COPD diagnosis
- at least 10 pack-year smoking history
- post-albuterol/salbutamol FEV1/FVC ratio of <0.70 and post-albuterol/salbutamol FEV1 greater than or equal to 35% and less than or equal to 80% of predicted normal
Exclusion Criteria:
- Pregant or lactating women or women planning to become pregnant during the study
- current diagnosis of asthma
- other respiratory disorders other than COPD
- other diseases/abnormalities that are uncontrolled including cancer not in remission for at least 5 years
- chest x-ray or CT scan with clinically significant abnormalities not believed to be due to COPD
- hypersensitivity to anticholinergics, beta-agonists, lactose/milk protein or magnesium stearate or medical conditions associated with inhaled anticholinergics
- hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1
- lung volume reduction surgery within 12 months prior to Visit 1
- abnormal and clinically significant ECG at Visit 1
- abnormal and clinically significant Holter monitor finding at Visit 1
- significantly abnormal finding from laboratory tests at Visit 1
- unable to withhold albuterol/salbutamol and/or ipratropium bromide at least 4 hours prior to spirometry at each visit
- use of depot corticosteroids within 12 weeks of Visit 1
- use of oral or parenteral corticosteroids within 6 weeks of Visit 1
- use of anitbiotics for lower respiratory tract infection within 6 weeks of Visit 1
- use of cytochrome P450 3A4 inhibitors within 6 weeks of Visit 1
- us of long-acting beta-agonist (LABA)/inhaled corticosteroid (ICS) products if LABA/ICS therapy is discontinued completely within 30 days of Visit 1
- use of ICS at a dose of >10000mcg/day of fluticasone propionate or equivalent within 30 days of Visit 1
- initiation or discontinuation of ICS within 30 days of Visit 1
- use of tiotropium within 14 days of Visit 1
- use of roflumilast within 14 days of Visit 1
- use of theophyllines within 48 hours of Visit 1
- use of oral leukotriene inhibitors within 48 hours prior to Visit 1
- use of long-acting oral beta-agonists within 48 hours of Visit 1
- use of short-acting oral beta-agonists within 12 hours of Visit 1
- use of inhaled long-acting beta-agonists within 48 hours prior to Visit 1
- use of LABA/ICS combination products only if discontinuing LABA therapy and switching to ICS monotherapy within 48 hours of Visit 1 for the LABA component
- use of sodium cromoglycate or nedocromil sodium within 24 hours of Visit 1
- use of inhaled short acting beta-agonists within 4 hours of Visit 1
- use of inhaled short-acting anticholinergics within 4 hours of Visit 1
- use of inhaled short-acting anticholinergic/short-acting beta2-agonist combination products within 4 hours of Visit 1
- use of any other investigational medication within 30 days or 5 drug half-lives (whichever is longer) of Visit 1
- long-term oxygen therapy prescribed for >12 hours per day
- regular use of short-acting bronchodilators
- use of CPAP or NIPPV
- participation in the maintenance phase of a pulmonary rehabilitation program
- known or suspected history of alcohol or drug abluse with 2 years prior to Visit 1
- anyone affiliated with the investigator site (e.g., investigator, study coordinator, etc.)
- previous use of GSK573719, GW642444 , GSK573719/GW642444 combination, GSK233705/GW642444 combination, or Fluticasone Furoate/GW642444 combination
Contacts and Locations
Show 53 Study Locations| Study Director: | GSK Clinical Trials | GlaxoSmithKline |
More Information
No publications provided
| Responsible Party: | GlaxoSmithKline |
| ClinicalTrials.gov Identifier: | NCT01316887 History of Changes |
| Other Study ID Numbers: | 113359 |
| Study First Received: | March 15, 2011 |
| Last Updated: | January 10, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by GlaxoSmithKline:
|
Chronic Obstructive Pulmonary Disease COPD nDPI long-acting beta agonist |
long-acting muscarinic antagonist tolerability safety |
Additional relevant MeSH terms:
|
Chronic Disease Lung Diseases Respiration Disorders Pulmonary Disease, Chronic Obstructive Lung Diseases, Obstructive Disease Attributes Pathologic Processes Respiratory Tract Diseases |
Muscarinic Antagonists Cholinergic Antagonists Cholinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on June 18, 2013