Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Spirometry, COPD
Brief summary
The purpose of the study is to determine the efficacy and safety of the combination of ADVAIR DISKUS® 250/50mcg (FLUTICASONE PROPIONATE/SALMETEROL COMBINATION PRODUCT) plus SPIRIVA® HANDIHALER® inhaler 18mcg (TIOTROPIUM) compared to SPIRIVA® HANDIHALER® inhaler 18mcg (TIOTROPIUM) in patients with COPD. SPIRIVA® and HANDIHALER® are trade marks of Boehringer Ingelheim Pharma GmbH & Co. KG. ADVAIR DISKUS® are registered trademarks of the GSK group of companies.
Interventions
DRUGTiotropium Bromide
Long-acting muscarinic antagonist
Inhaled corticosteroid plus long-acting bronchodilator
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* COPD diagnosis * At least 10 pack year smoking history * Post-albuterol FEV1 greater than or equal to 40% to less than or equal to 80% of predicted normal * An FEV1/FVC ratio of less than or equal to 0.70
Exclusion criteria
* Current diagnosis of asthma * Other respiratory disorder other than COPD * Abnormal and clinical significant ECG * Chest x-ray clinically significant abnormality not believed to be due to COPD * Body Mass Index of greater than or equal to 40/kg/m2 * Use of Long Term Oxygen Therapy * Lung resection surgery * Women pregnant or lactating at Visit 1 * Previously diagnosed cancer unless in complete remission for 2 years at Visit 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in AM (Morning, Approximately 6-9 AM) Pre-dose Forced Expiratory Volume in One Second (FEV1) at Endpoint | Baseline and Endpoint (defined as the last recorded measure [taken up to Week 24] of AM pre-dose FEV1 for each participant) | Change from baseline was calculated as the Endpoint (defined as the last recorded measure of AM pre-dose FEV1 for each participant) value minus the baseline value. FEV1 is defined as the amount of air expelled from the lungs in one second after a full inspiration and is a measure of pulmonary function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in 2 Hour Post-dose FEV1 at Endpoint | Baseline and Endpoint (defined as the last recorded measure [taken up to Week 24] of 2 hour post-dose FEV1 for each participant) | Change from baseline was calculated as the Endpoint (defined as the last recorded measure of 2 hour post-dose FEV1 for each participant) value minus the baseline value. FEV1 is defined as the amount of air expelled from the lungs in one second after a full inspiration and is a measure of pulmonary function. |
| Mean Change From Baseline in AM (Morning, Approximately 6-9 AM) Pre-dose Forced Vital Capacity (FVC) at Endpoint | Baseline and Endpoint (defined as the last recorded measure [up to Week 24] of AM pre-dose FVC for each participant) | Change from baseline was calculated as the Endpoint (defined as the last recorded measure of AM pre-dose FVC fore each participant) value minus the baseline value. FVC is defined as the amount of air that can forcibly be blown out after a full inspiration. |
| Mean Change From Baseline in 2 Hour Post-dose FVC at Endpoint | Baseline and Endpoint (defined as the last recorded measure of 2 hour post-dose FVC [up to Week 24] for each participant) | Change from baseline was calculated as the Endpoint (defined as the last recorded measure of 2 hour post-dose FVC for each participant) value minus the baseline value. FVC is defined as the amount of air that can forcibly be blown out after a full inspiration (FVC). |
| Mean Change From Baseline in AM (Morning, Approximately 6-9 AM) Pre-Dose Inspiratory Capacity (IC) at Endpoint | Baseline and Endpoint (defined as the last recorded measure of AM pre-dose IC [up to Week 24] for each participant) | Change from baseline was calculated as the Endpoint (defined as the last recorded measure of AM pre-dose IC for each participant) value minus the baseline value. IC is defined as the amount of air that can be inhaled after a normal expiration. IC is a measure of pulmonary function. |
| Mean Change From Baseline in Scores on the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) at Endpoint | Baseline and Endpoint (defined as the last recorded score [up to Week 24 or the early withdrawal visit] on each of the questions on this questionnaire) | The CRQ-SAS measures 4 domains of functioning of participants with COPD: mastery (amount of control the participant feels he/she has over COPD symptoms); fatigue (how tired the participant feels); emotional function (how anxious/depressed the participant feels); and dyspnea (how short of breath the participant feels during physical activities). Each domain is measured on a scale of 1-7 (1=maximum impairment; 7=no impairment). Each domain score is calculated separately. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FSC + Tio Open-label tiotropium (Tio) 18 micrograms (mcg) once-daily (QD) plus double-blind Fluticasone Propionate/Salmeterol Combination (FSC) 250/50 mcg twice daily (BID) | 173 |
| Tiotropium Open-label Tio 18 mcg QD plus double-blind matching placebo DISKUS BID | 169 |
| Total | 342 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 10 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 8 | 5 |
| Overall Study | Physician Decision | 2 | 3 |
| Overall Study | Protocol Violation | 10 | 10 |
| Overall Study | Withdrawal by Subject | 4 | 13 |
Baseline characteristics
| Characteristic | Tiotropium | Total | FSC + Tio |
|---|---|---|---|
| Age, Continuous | 61.0 Years STANDARD_DEVIATION 9.41 | 61.2 Years STANDARD_DEVIATION 8.98 | 61.3 Years STANDARD_DEVIATION 8.56 |
| Race/Ethnicity, Customized African American/African Heritage | 7 participants | 14 participants | 7 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 162 participants | 327 participants | 165 participants |
| Sex: Female, Male Female | 96 Participants | 182 Participants | 86 Participants |
| Sex: Female, Male Male | 73 Participants | 160 Participants | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 34 / 173 | 29 / 169 |
| serious Total, serious adverse events | 7 / 173 | 13 / 169 |
Outcome results
Primary
Mean Change From Baseline in AM (Morning, Approximately 6-9 AM) Pre-dose Forced Expiratory Volume in One Second (FEV1) at Endpoint
Change from baseline was calculated as the Endpoint (defined as the last recorded measure of AM pre-dose FEV1 for each participant) value minus the baseline value. FEV1 is defined as the amount of air expelled from the lungs in one second after a full inspiration and is a measure of pulmonary function.
Time frame: Baseline and Endpoint (defined as the last recorded measure [taken up to Week 24] of AM pre-dose FEV1 for each participant)
Population: Intent-to-Treat (ITT) Population: all participants randomized to study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSC + Tio | Mean Change From Baseline in AM (Morning, Approximately 6-9 AM) Pre-dose Forced Expiratory Volume in One Second (FEV1) at Endpoint | 101 milliliters (ml) | Standard Error 21.8 |
| Tiotropium | Mean Change From Baseline in AM (Morning, Approximately 6-9 AM) Pre-dose Forced Expiratory Volume in One Second (FEV1) at Endpoint | -16 milliliters (ml) | Standard Error 20.4 |
p-value: <0.001ANCOVA
Secondary
Mean Change From Baseline in 2 Hour Post-dose FEV1 at Endpoint
Change from baseline was calculated as the Endpoint (defined as the last recorded measure of 2 hour post-dose FEV1 for each participant) value minus the baseline value. FEV1 is defined as the amount of air expelled from the lungs in one second after a full inspiration and is a measure of pulmonary function.
Time frame: Baseline and Endpoint (defined as the last recorded measure [taken up to Week 24] of 2 hour post-dose FEV1 for each participant)
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSC + Tio | Mean Change From Baseline in 2 Hour Post-dose FEV1 at Endpoint | 233 ml | Standard Error 23.1 |
| Tiotropium | Mean Change From Baseline in 2 Hour Post-dose FEV1 at Endpoint | 77 ml | Standard Error 20.6 |
p-value: <0.001ANCOVA
Secondary
Mean Change From Baseline in 2 Hour Post-dose FVC at Endpoint
Change from baseline was calculated as the Endpoint (defined as the last recorded measure of 2 hour post-dose FVC for each participant) value minus the baseline value. FVC is defined as the amount of air that can forcibly be blown out after a full inspiration (FVC).
Time frame: Baseline and Endpoint (defined as the last recorded measure of 2 hour post-dose FVC [up to Week 24] for each participant)
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSC + Tio | Mean Change From Baseline in 2 Hour Post-dose FVC at Endpoint | 265 ml | Standard Error 35.9 |
| Tiotropium | Mean Change From Baseline in 2 Hour Post-dose FVC at Endpoint | 87 ml | Standard Error 31.2 |
p-value: <0.001ANCOVA
Secondary
Mean Change From Baseline in AM (Morning, Approximately 6-9 AM) Pre-dose Forced Vital Capacity (FVC) at Endpoint
Change from baseline was calculated as the Endpoint (defined as the last recorded measure of AM pre-dose FVC fore each participant) value minus the baseline value. FVC is defined as the amount of air that can forcibly be blown out after a full inspiration.
Time frame: Baseline and Endpoint (defined as the last recorded measure [up to Week 24] of AM pre-dose FVC for each participant)
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSC + Tio | Mean Change From Baseline in AM (Morning, Approximately 6-9 AM) Pre-dose Forced Vital Capacity (FVC) at Endpoint | 95 ml | Standard Error 32.7 |
| Tiotropium | Mean Change From Baseline in AM (Morning, Approximately 6-9 AM) Pre-dose Forced Vital Capacity (FVC) at Endpoint | -28 ml | Standard Error 30.6 |
p-value: 0.006ANCOVA
Secondary
Mean Change From Baseline in AM (Morning, Approximately 6-9 AM) Pre-Dose Inspiratory Capacity (IC) at Endpoint
Change from baseline was calculated as the Endpoint (defined as the last recorded measure of AM pre-dose IC for each participant) value minus the baseline value. IC is defined as the amount of air that can be inhaled after a normal expiration. IC is a measure of pulmonary function.
Time frame: Baseline and Endpoint (defined as the last recorded measure of AM pre-dose IC [up to Week 24] for each participant)
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSC + Tio | Mean Change From Baseline in AM (Morning, Approximately 6-9 AM) Pre-Dose Inspiratory Capacity (IC) at Endpoint | 107 ml | Standard Error 28.4 |
| Tiotropium | Mean Change From Baseline in AM (Morning, Approximately 6-9 AM) Pre-Dose Inspiratory Capacity (IC) at Endpoint | -8 ml | Standard Error 28.1 |
p-value: <0.001ANCOVA
Secondary
Mean Change From Baseline in Scores on the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) at Endpoint
The CRQ-SAS measures 4 domains of functioning of participants with COPD: mastery (amount of control the participant feels he/she has over COPD symptoms); fatigue (how tired the participant feels); emotional function (how anxious/depressed the participant feels); and dyspnea (how short of breath the participant feels during physical activities). Each domain is measured on a scale of 1-7 (1=maximum impairment; 7=no impairment). Each domain score is calculated separately.
Time frame: Baseline and Endpoint (defined as the last recorded score [up to Week 24 or the early withdrawal visit] on each of the questions on this questionnaire)
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FSC + Tio | Mean Change From Baseline in Scores on the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) at Endpoint | Mastery | 0.28 points on a scale | Standard Error 0.078 |
| FSC + Tio | Mean Change From Baseline in Scores on the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) at Endpoint | Fatigue | 0.23 points on a scale | Standard Error 0.094 |
| FSC + Tio | Mean Change From Baseline in Scores on the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) at Endpoint | Emotional Function | 0.24 points on a scale | Standard Error 0.072 |
| FSC + Tio | Mean Change From Baseline in Scores on the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) at Endpoint | Dyspnea | 0.21 points on a scale | Standard Error 0.091 |
| Tiotropium | Mean Change From Baseline in Scores on the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) at Endpoint | Dyspnea | 0.19 points on a scale | Standard Error 0.091 |
| Tiotropium | Mean Change From Baseline in Scores on the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) at Endpoint | Mastery | 0.04 points on a scale | Standard Error 0.09 |
| Tiotropium | Mean Change From Baseline in Scores on the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) at Endpoint | Emotional Function | 0.16 points on a scale | Standard Error 0.073 |
| Tiotropium | Mean Change From Baseline in Scores on the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) at Endpoint | Fatigue | 0.17 points on a scale | Standard Error 0.091 |
p-value: 0.069ANCOVA
p-value: 0.47ANCOVA
p-value: 0.394ANCOVA
p-value: 0.879ANCOVA