Clinical trial NCT01316887: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: Chronic Obstructive Pulmonary Disease
COPD
nDPI
long-acting beta agonist
long-acting muscarinic antagonist
tolerability
safety
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-03-16
Enrollment: 563
Sex: ALL
Minimum age (years): 40
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

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 criteria: 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

Primary outcomes:
measure: Number of Participants With Any On-treatment Adverse Event (AE) or Any Serious Adverse Event (SAE)
timeFrame: From the start of study drug up to 52 weeks
Secondary outcomes:
measure: Number of Participants With at Least One Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Over the Course of the 52-week Treatment Period
timeFrame: From the start of study drug up to 52 weeks
measure: Time to the First On-treatment COPD Exacerbation
timeFrame: From the start of study drug up to 52 weeks
measure: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyl Transferase (GGT) at Months 3, 6, 9, and 12
timeFrame: Baseline; Months 3, 6, 9, and 12
measure: Change From Baseline in Albumin, Total Protein, and Hemoglobin at Months 3, 6, 9, and 12
timeFrame: Baseline; Months 3, 6, 9, and 12
measure: Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Months 3, 6, 9, and 12
timeFrame: Baseline; Months 3, 6, 9, and 12
measure: Change From Baseline in Creatinine, Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Uric Acid at Months 3, 6, 9, and 12
timeFrame: Baseline; Months 3, 6, 9, and 12
measure: Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood at Months 3, 6, 9, and 12
timeFrame: Baseline; Months 3, 6, 9, and 12
measure: Change From Baseline in Eosinophil Count, Platelet Count, and White Blood Cell (WBC) Count at Months 3, 6, 9, and 12
timeFrame: Baseline; Months 3, 6, 9, and 12
measure: Change From Baseline in Hematocrit at Months 3, 6, 9, and 12
timeFrame: Baseline; Months 3, 6, 9, and 12
measure: Change From Baseline to Maximum Systolic Blood Pressure (SBP) and Change From Baseline to Minimum Diastolic Blood Pressure (DBP) Over the Course of the 52-week Treatment Period
timeFrame: Baseline; from the start of study drug up to 52 weeks
measure: Maximum Change From Baseline in Pulse Rate Over the Course of the 52-week Treatment Period
timeFrame: Baseline; from the start of study drug up to 52 weeks
measure: Maximum Change From Baseline in the Electrocardiogram (ECG) Parameters of QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB), QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF), and PR Interval Over the Course of the 52-week
timeFrame: Baseline; from the start of study drug up to 52 weeks
measure: Maximum Change From Baseline in the ECG Parameter of Heart Rate Over the Course of the 52-week Treatment Period
timeFrame: Baseline; from the start of study drug up to 52 weeks
measure: Number of Participants With the Indicated ECG Result Interpretations at Any Time Post-Baseline
timeFrame: From the start of study drug up to 52 weeks
measure: Number of Participants With the Indicated Change From Screening to Any Time Post-Baseline in Holter ECG Interpretation
timeFrame: Screening; from the start of study drug up to 52 weeks
measure: Change From Baseline in the Mean Number of Puffs of Rescue Medication (Salbutamol and/or Ipratropium Bromide) Per Day Over the Course of the 52-week Treatment Period
timeFrame: Baseline; from the start of study drug up to 52 weeks
measure: Change From Baseline in the Percentage of Rescue-free Days Over the Course of the 52-week Treatment Period
timeFrame: From the start of study drug up to 52 weeks
measure: Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Months 1, 3, 6, 9, and 12
timeFrame: Baseline; Months 1, 3, 6, 9, and 12
Other outcomes:
Locations:
city: Mobile
country: United States
facility: GSK Investigational Site
state: Alabama
city: Sunset
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Plymouth
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Erie
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Union
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Corsicana
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Morgantown
country: United States
facility: GSK Investigational Site
state: West Virginia
city: Puente Alto - Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Talca
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
city: Bacau
country: Romania
facility: GSK Investigational Site
city: Brasov
country: Romania
facility: GSK Investigational Site
city: Brasov
country: Romania
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Pitesti
country: Romania
facility: GSK Investigational Site
city: Ploiesti
country: Romania
facility: GSK Investigational Site
city: Ploiesti
country: Romania
facility: GSK Investigational Site
city: Timisoara
country: Romania
facility: GSK Investigational Site
city: Ekaterinburg
country: Russian Federation
facility: GSK Investigational Site
city: Ivanovo
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Novgorod
country: Russian Federation
facility: GSK Investigational Site
city: Penza
country: Russian Federation
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Shakhty, Rostov Region
country: Russian Federation
facility: GSK Investigational Site
city: Sochi
country: Russian Federation
facility: GSK Investigational Site
city: St'Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Tomsk
country: Russian Federation
facility: GSK Investigational Site
city: Tumen
country: Russian Federation
facility: GSK Investigational Site
city: Vladivostok
country: Russian Federation
facility: GSK Investigational Site
city: Bratislava
country: Slovakia
facility: GSK Investigational Site
city: Bratislava
country: Slovakia
facility: GSK Investigational Site
city: Poprad
country: Slovakia
facility: GSK Investigational Site
city: Povazska Bystrica
country: Slovakia
facility: GSK Investigational Site
city: Sala
country: Slovakia
facility: GSK Investigational Site
city: Zilina
country: Slovakia
facility: GSK Investigational Site
city: Benoni
country: South Africa
facility: GSK Investigational Site
state: Gauteng
city: Bellville
country: South Africa
facility: GSK Investigational Site
city: Bloemfontein
country: South Africa
facility: GSK Investigational Site
city: Durban
country: South Africa
facility: GSK Investigational Site
city: Gatesville
country: South Africa
facility: GSK Investigational Site
city: Mowbray
country: South Africa
facility: GSK Investigational Site
city: Somerset West
country: South Africa
facility: GSK Investigational Site
city: Tygerberg
country: South Africa
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: