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The purpose of this study is to evaluate the effects on lung function of a combination of ADOAIR 50/250mcg twice daily plus tiotropium bromide 18mcg once daily compared with the individual treatments (tiotropium bromide 18mcg once daily alone and ADOAIR 50/250mcg twice daily alone) in Japanese subjects with COPD. The study will utilize a three-way cross-over design with a 2-week wash-out period between each 4-week consecutive treatment period. The aim is to support the rationale for "triple combination" therapy by demonstrating that treatment with both ADOAIR and tiotropium can potentially produce improved, clinically relevant effects compared with either treatment alone.
This study will utilize a range of lung function measures in order to fully assess the benefits of triple therapy. The primary endpoint will be based on airways conductance measured using plethysmography (sGaw measured over 4hours post dose (AUC 0-4hr) on Day 28). Secondary endpoints will include lung function measures based on plethysmography and spirometry. The lung function measures will be supported by measurement of the use of relief salbutamol .
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| fluticasone propionate/salmeterol | Active Comparator | 250mcg fluticasone + 50 mcg salmeterol, twice daily 4 week treatment in each treatment sequence (crossover design) |
|
| tiotropium bromide | Active Comparator | 18 mcg tiotropium bromide, once daily 4 week treatment in each treatment sequence (crossover design) |
|
| fluticasone propionate/salmeterol plus tiotropium bromide | Active Comparator | 250mcg fluticasone + 50 mcg salmeterol, twice daily plus 18 mcg tiotropium bromide, once daily 4 week treatment in each treatment sequence (crossover design) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| fluticasone propionate/salmeterol | Drug | 250mcg fluticasone + 50 mcg salmeterol, twice daily 4 week treatment in each treatment sequence (crossover design) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve Calculated From 0 to 4 Hours (AUC[0-4hr]) Specific Conductance (sGaw) After the Morning Dose of Study Medication at Day 28 of Each Treatment Period | sGaw is a measure of airways conductance and is intimately related to the diameter of the airways and consequently the level of bronchodilation. Plethysmography was performed to assess sGaw. The AUC was determined by using the trapezoidal rule and then dividing by the relevant time interval. A natural logarithmic transformation was applied and the data was analyzed by a mixed model including treatment, period and Baseline sGaw fitted as fixed effects and participants fitted as a random effect. Treatment ratios of all statistical comparisons were calculated by taking the anti-log of the difference between the Least Square (LS) means. | Day 28 of each treatment period (up to 35 days) |
| Measure | Description | Time Frame |
|---|---|---|
| AUC (0-4hr) Specific Airway Resistance (sRaw) After the Morning Dose of Each Study Medication at Day 28 of Each Treatment Period | sRaw is a measure of airways resistance and is intimately related to the diameter of the airways and consequently the level of bronchodilation. Plethysmography was performed to assess sRaw. The AUC was determined by using the trapezoidal rule and then dividing by the relevant time interval. A natural logarithmic transformation was applied and the data was analyzed by a mixed model including treatment, period and Baseline sRaw fitted as fixed effects and participants fitted as a random effect. Treatment ratios of all statistical comparisons were calculated by taking the anti-log of the difference between the LS means. |
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Inclusion Criteria:
(QTc(F) <450msec, or <480 in subjects with right bundle branch block, should be confirmed by the mean of three readings or one reading)
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Hokkaido | 070-8644 | Japan | |||
| GSK Investigational Site |
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| Label | URL |
|---|---|
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 116572 | Study Protocol | View IPD |
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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Participants, who met eligibility criteria, completed a 2-week Run-in Period prior to being randomized to 1 of 6 treatment sequences. The treatment phase was comprised of three 4 week treatment periods, each separated by a 2-week washout period.
A total of 53 Japanese participants with moderate or severe chronic obstructive pulmonary disease (COPD) entered the run-in period.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1: Ado 50/250 µg+Tio 18 µg, Tio 18 µg, Ado 50/250 µg | Participants received salmeterol xinafoate/fluticasone propionate (Ado) 50/250 micrograms (µg) twice daily (BID) (morning and evening) plus tiotropium bromide (Tio) 18 µg once daily (QD) (morning), Tio 18 µg QD (morning) plus Ado matching placebo BID (morning and evening), and Ado 50/250 µg BID (morning and evening) plus Tio matching placebo QD (morning) in Treatment Periods 1, 2, and 3, respectively. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Ado 50/250 µg and its matching placebo were administered via a dry powder inhaler and Tio 18 µg and its matching placebo were administered via a HandiHaler inhaler. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period 1 (4 Weeks) |
|
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| tiotropium bromide | Drug | 18 mcg tiotropium bromide, once daily 4 week treatment in each treatment sequence (crossover design) |
|
| fluticasone propionate/salmeterol plus tiotropium bromide | Drug | 250mcg fluticasone + 50 mcg salmeterol, twice daily plus 18 mcg tiotropium bromide, once daily 4 week treatment in each treatment sequence (crossover design) |
|
|
| Day 28 of each treatment period (up to 35 days) |
| Post-dose sGaw at 30, 75, 120 and 240 Minutes Post Dose at Day 28 of Each Treatment Period | sGaw is a measure of airways conductance and is intimately related to the diameter of the airways and consequently the level of bronchodilation. Plethysmography was performed to assess sGaws. A natural logarithmic transformation was applied and the data was analyzed by a mixed model including treatment, time, period, a treatment by time interaction and Baseline sGaw fitted as fixed effects and participant fitted as a random effect. | Day 28 of each treatment period (up to 35 days) |
| Post-dose sRaw at 30, 75, 120 and 240 Minutes Post Dose at Day 28 of Each Treatment Period | sRaw is a measure of airways resistance and is intimately related to the diameter of the airways and consequently the level of bronchodilation. Plethysmography was performed to assess sRaw. A natural logarithmic transformation was applied and the data was analysed by a mixed model including treatment, time, period, a treatment by time interaction and Baseline sRaw fitted as fixed effects and participant fitted as a random effect. | Day 28 of each treatment period (up to 35 days) |
| Trough Forced Expiratory Volume in One Second (FEV1), Forced Vital Capacity (FVC), Inspiratory Capacity (IC), RV, TLC, and TGV at Each Clinic Visit Prior to the Morning Dose and Before the Use of Rescue Medication at Day 28 of Each Treatment Period | FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the amount of air that can forcibly be blown out after a full inspiration. FEV1 and FVC data was obtained by spirometry measurements. 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. Total lung capacity (TLC) is the maximum volume to which the lungs can be expanded with the greatest possible inspiratory effort; it is equal to the vital capacity (VC) plus the residual volume (RV). RV is defined as the volume of air remaining in the lungs. after a maximal exhalation. Thoracic gas volume at functional residual capacity (TGV) is defined as the volume of intrathoracic gas at the time the airway is occluded for the plethysmographic measurement at the end of a normal expiration. Trough values were the values taken pre-dose. | Day 28 of each treatment period (up to 35 days) |
| Trough FEV1/FVC Ratio, at Each Clinic Visit Prior to the Morning Dose and Before the Use of Rescue Medication at Day 28 of Each Treatment Period | FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the amount of air that can forcibly be blown out after a full inspiration. FEV1 and FVC data was obtained by spirometry measurements. Trough values were the values taken pre-dose. | Day 28 of each treatment period (up to 35 days) |
| Trough sRaw Measured at Each Clinic Visit Prior to the Morning Dose and Before the Use of Rescue Medication at Day 28 of Each Treatment Period | sRaw is a measure of airways resistance and is intimately related to the diameter of the airways and consequently the level of bronchodilation. Trough values were the values taken pre-dose. | Day 28 of each treatment period (up to 35 days) |
| Trough sGaw Measured at Each Clinic Visit Prior to the Morning Dose and Before the Use of Rescue Medication at Day 28 of Each Treatment Period | sGaw is a measure of airways conductance and is intimately related to the diameter of the airways and consequently the level of bronchodilation. Trough values were the values taken pre-dose. | Day 28 of each treatment period (up to 35 days) |
| Post-dose FEV1, FVC, IC, RV, TLC and TGV (Measured at Trough) at Day 28 of Each Treatment Period | FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the amount of air that can forcibly be blown out after a full inspiration. FEV1 and FVC data was obtained by spirometry measurements. 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. Total lung capacity (TLC) is the maximum volume to which the lungs can be expanded with the greatest possible inspiratory effort; it is equal to the vital capacity (VC) plus the RV. RV is defined as the volume of air remaining in the lungs after a maximal exhalation. Thoracic gas volume at functional residual capacity (TGV) is defined as the volume of intrathoracic gas at the time the airway is occluded for the plethysmographic measurement at the end of a normal expiration. | Day 28 of each treatment period (up to 35 days) |
| Post-dose FEV1/FVC Ratio (Measured at Trough) at Day 28 of Each Treatment Period | FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the amount of air that can forcibly be blown out after a full inspiration. FEV1 and FVC data was obtained by spirometry measurements. | Day 28 of each treatment period (up to 35 days) |
| Use of Rescue Medication (Number of Occasions Per 24-hour Period) as Recorded in the Daily Record Card at Day 28 of Each Treatment Period | Participants were given daily record cards for daily completion during the run-in, washout and treatment periods. Each morning, participants recorded the number of occasions in the last 24 hours when they had used their rescue medication (salbutamol) for symptomatic relief of COPD symptoms. | Day 28 of each treatment period (up to 35 days) |
| Ibaraki |
| 319-1113 |
| Japan |
| GSK Investigational Site | Osaka | 530-0001 | Japan |
For additional information about this study please refer to the GSK Clinical Study Register |
| 116572 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116572 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116572 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116572 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| FG001 | Sequence 2: Tio 18 µg, Ado 50/250 µg, Ado 50/250 µg+Tio 18 µg | Participants received Tio 18 µg QD (morning) plus Ado matching placebo BID (morning and evening), Ado 50/250 µg BID (morning and evening) plus Tio matching placebo QD (morning), and Ado 50/250 µg BID plus Tio 18 µg QD (morning) in Treatment Periods 1, 2, and 3, respectively. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Ado 50/250 µg and its matching placebo were administered via a dry powder inhaler and Tio 18 µg and its matching placebo were administered via a HandiHaler inhaler. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. |
| FG002 | Sequence 3: Ado 50/250 µg, Ado 50/250 µg+Tio 18 µg, Tio 18 µg | Participants received Ado 50/250 µg BID (morning and evening) plus Tio matching placebo QD (morning), Ado 50/250 µg BID plus Tio 18 µg QD (morning), and Tio 18 µg QD (morning) plus Ado matching placebo BID (morning and evening) in Treatment Period 1, 2, and 3, respectively. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Ado 50/250 µg and its matching placebo were administered via a dry powder inhaler and Tio 18 µg and its matching placebo were administered via HandiHaler inhaler. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. |
| FG003 | Sequence 4: Ado 50/250 µg, Tio 18 µg, Ado 50/250 µg+Tio 18 µg | Participants received Ado 50/250 µg BID (morning and evening) plus Tio matching placebo QD (morning), Tio 18 µg QD (morning) plus Ado matching placebo BID (morning and evening), and Ado 50/250 µg BID plus Tio 18 µg QD (morning) in Treatment Period 1, 2, and 3, respectively. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Ado 50/250 µg and its matching placebo were administered via a dry powder inhaler and Tio 18 µg and its matching placebo were administered via a HandiHaler inhaler. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. |
| FG004 | Sequence 5: Ado 50/250 µg+Tio 18 µg, Ado 50/250 µg, Tio 18 µg | Participants received Ado 50/250 µg BID plus Tio 18 µg QD (morning), Ado 50/250 µg BID (morning and evening) plus Tio matching placebo QD (morning) and Tio 18 µg QD (morning) plus Ado matching placebo BID (morning and evening) in Treatment Period 1, 2, and 3, respectively. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Ado 50/250 µg and its matching placebo were administered via a dry powder inhaler and Tio 18 µg and its matching placebo were administered via a HandiHaler inhaler. Participants were provided with salbutamol inhaler to be used as relief medication throughout the study. |
| FG005 | Sequence 6: Tio 18 µg, Ado 50/250 µg+Tio 18 µg, Ado 50/250 µg | Participants received Tio 18 µg QD (morning) plus Ado matching placebo BID (morning and evening), Ado 50/250 µg BID plus Tio 18 µg QD (morning), and Ado 50/250 µg BID (morning and evening) plus Tio matching placebo QD (morning) in Treatment Period 1, 2, and 3, respectively. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Ado 50/250 µg and its matching placebo were administered via a dry powder inhaler and Tio 18 µg and its matching placebo were administered via a HandiHaler inhaler. Participants were provided with salbutamol inhaler to be used as relief medication throughout the study. |
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| NOT COMPLETED |
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| Washout Period 1 (2 Weeks) |
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| Treatment Period 2 (4 Weeks) |
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| Washout Period 2 (2 Weeks) |
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| Treatment Period 3 (4 Weeks) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Ado 50/250 µg+Tio 18 µg, Ado 50/250 µg, Tio 18 µg | All participants received one of the following 3 treatments in one of three 4-week treatment periods separated by a 2-week washout period:Ado 50/250 µg BID (morning and evening) + Tio 18 µg QD (morning), Ado 50/250 µg BID (morning and evening) + Tio matching placebo QD (morning), and Tio 18 µg QD (morning) + Ado matching placebo BID (morning and evening). Participants were randomized to one of the 6 following treatment sequences: (1) Ado 50/250 µg+Tio 18 µg, Tio 18 µg, Ado 50/250 µg (2) Tio 18 µg, Ado 50/250 µg, Ado 50/250 µg+Tio 18 µg (3) Ado 50/250 µg, Ado 50/250 µg+Tio 18 µg, Tio 18 µg (4) Ado 50/250 µg, Tio 18 µg, Ado 50/250 µg+Tio 18 µg (5) Ado 50/250 µg+Tio 18 µg, Ado 50/250 µg, Tio 18 µg (6) Tio 18 µg, Ado 50/250 µg+Tio 18 µg, Ado 50/250 µg. Ado 50/250 µg and its matching placebo were administered via DISKUS inhaler and Tio 18 µg and its matching placebo were administered via HandiHaler inhaler. Participants used salbutamol inhaler as relief medication throughout the study. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Curve Calculated From 0 to 4 Hours (AUC[0-4hr]) Specific Conductance (sGaw) After the Morning Dose of Study Medication at Day 28 of Each Treatment Period | sGaw is a measure of airways conductance and is intimately related to the diameter of the airways and consequently the level of bronchodilation. Plethysmography was performed to assess sGaw. The AUC was determined by using the trapezoidal rule and then dividing by the relevant time interval. A natural logarithmic transformation was applied and the data was analyzed by a mixed model including treatment, period and Baseline sGaw fitted as fixed effects and participants fitted as a random effect. Treatment ratios of all statistical comparisons were calculated by taking the anti-log of the difference between the Least Square (LS) means. | Modified Intent-to-Treat (mITT) Population: all randomized participants who received at least one dose of study medication and completed at least two treatment periods and also had a Baseline and at least one on treatment sGaw assessment measure. | Posted | Geometric Mean | Standard Error | 1/kilopascal*second (1/kPa*s) | Day 28 of each treatment period (up to 35 days) |
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| Secondary | AUC (0-4hr) Specific Airway Resistance (sRaw) After the Morning Dose of Each Study Medication at Day 28 of Each Treatment Period | sRaw is a measure of airways resistance and is intimately related to the diameter of the airways and consequently the level of bronchodilation. Plethysmography was performed to assess sRaw. The AUC was determined by using the trapezoidal rule and then dividing by the relevant time interval. A natural logarithmic transformation was applied and the data was analyzed by a mixed model including treatment, period and Baseline sRaw fitted as fixed effects and participants fitted as a random effect. Treatment ratios of all statistical comparisons were calculated by taking the anti-log of the difference between the LS means. | mITT Population | Posted | Geometric Mean | Standard Error | kPa*s | Day 28 of each treatment period (up to 35 days) |
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| Secondary | Post-dose sGaw at 30, 75, 120 and 240 Minutes Post Dose at Day 28 of Each Treatment Period | sGaw is a measure of airways conductance and is intimately related to the diameter of the airways and consequently the level of bronchodilation. Plethysmography was performed to assess sGaws. A natural logarithmic transformation was applied and the data was analyzed by a mixed model including treatment, time, period, a treatment by time interaction and Baseline sGaw fitted as fixed effects and participant fitted as a random effect. | mITT Population | Posted | Geometric Mean | Standard Error | 1/kPa*s | Day 28 of each treatment period (up to 35 days) |
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| Secondary | Post-dose sRaw at 30, 75, 120 and 240 Minutes Post Dose at Day 28 of Each Treatment Period | sRaw is a measure of airways resistance and is intimately related to the diameter of the airways and consequently the level of bronchodilation. Plethysmography was performed to assess sRaw. A natural logarithmic transformation was applied and the data was analysed by a mixed model including treatment, time, period, a treatment by time interaction and Baseline sRaw fitted as fixed effects and participant fitted as a random effect. | mITT Population | Posted | Geometric Mean | Standard Error | kPa*s | Day 28 of each treatment period (up to 35 days) |
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| Secondary | Trough Forced Expiratory Volume in One Second (FEV1), Forced Vital Capacity (FVC), Inspiratory Capacity (IC), RV, TLC, and TGV at Each Clinic Visit Prior to the Morning Dose and Before the Use of Rescue Medication at Day 28 of Each Treatment Period | FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the amount of air that can forcibly be blown out after a full inspiration. FEV1 and FVC data was obtained by spirometry measurements. 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. Total lung capacity (TLC) is the maximum volume to which the lungs can be expanded with the greatest possible inspiratory effort; it is equal to the vital capacity (VC) plus the residual volume (RV). RV is defined as the volume of air remaining in the lungs. after a maximal exhalation. Thoracic gas volume at functional residual capacity (TGV) is defined as the volume of intrathoracic gas at the time the airway is occluded for the plethysmographic measurement at the end of a normal expiration. Trough values were the values taken pre-dose. | mITT Population | Posted | Least Squares Mean | Standard Error | Liters (L) | Day 28 of each treatment period (up to 35 days) |
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| Secondary | Trough FEV1/FVC Ratio, at Each Clinic Visit Prior to the Morning Dose and Before the Use of Rescue Medication at Day 28 of Each Treatment Period | FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the amount of air that can forcibly be blown out after a full inspiration. FEV1 and FVC data was obtained by spirometry measurements. Trough values were the values taken pre-dose. | mITT Population | Posted | Least Squares Mean | Standard Error | Ratio of FEV1/FVC | Day 28 of each treatment period (up to 35 days) |
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| Secondary | Trough sRaw Measured at Each Clinic Visit Prior to the Morning Dose and Before the Use of Rescue Medication at Day 28 of Each Treatment Period | sRaw is a measure of airways resistance and is intimately related to the diameter of the airways and consequently the level of bronchodilation. Trough values were the values taken pre-dose. | mITT Population | Posted | Geometric Mean | Standard Error | kPa*s | Day 28 of each treatment period (up to 35 days) |
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| Secondary | Trough sGaw Measured at Each Clinic Visit Prior to the Morning Dose and Before the Use of Rescue Medication at Day 28 of Each Treatment Period | sGaw is a measure of airways conductance and is intimately related to the diameter of the airways and consequently the level of bronchodilation. Trough values were the values taken pre-dose. | mITT Population | Posted | Geometric Mean | Standard Error | 1/kPa*s | Day 28 of each treatment period (up to 35 days) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Post-dose FEV1, FVC, IC, RV, TLC and TGV (Measured at Trough) at Day 28 of Each Treatment Period | FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the amount of air that can forcibly be blown out after a full inspiration. FEV1 and FVC data was obtained by spirometry measurements. 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. Total lung capacity (TLC) is the maximum volume to which the lungs can be expanded with the greatest possible inspiratory effort; it is equal to the vital capacity (VC) plus the RV. RV is defined as the volume of air remaining in the lungs after a maximal exhalation. Thoracic gas volume at functional residual capacity (TGV) is defined as the volume of intrathoracic gas at the time the airway is occluded for the plethysmographic measurement at the end of a normal expiration. | mITT Population | Posted | Least Squares Mean | Standard Error | Liters (L) | Day 28 of each treatment period (up to 35 days) |
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| Secondary | Post-dose FEV1/FVC Ratio (Measured at Trough) at Day 28 of Each Treatment Period | FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the amount of air that can forcibly be blown out after a full inspiration. FEV1 and FVC data was obtained by spirometry measurements. | mITT Population | Posted | Least Squares Mean | Standard Error | Ratio of FEV1/FVC | Day 28 of each treatment period (up to 35 days) |
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| Secondary | Use of Rescue Medication (Number of Occasions Per 24-hour Period) as Recorded in the Daily Record Card at Day 28 of Each Treatment Period | Participants were given daily record cards for daily completion during the run-in, washout and treatment periods. Each morning, participants recorded the number of occasions in the last 24 hours when they had used their rescue medication (salbutamol) for symptomatic relief of COPD symptoms. | mITT Population. Only those participants available who used rescue medication at the specified periods were analyzed (represented by n=X, X, X in the category titles). | Posted | Mean | Standard Deviation | Number of occasions | Day 28 of each treatment period (up to 35 days) |
|
Serious adverse events (SAEs) and non-serious AEs were collected from the start of administration of the study drug until follow-up contact (up to Week 18).
SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants randomized to treatment, who had taken at least one dose of study medication.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ado 50/250 µg BID+Tio 18 µg QD | Participants received Ado 50/250 µg BID (morning and evening) via a dry powder inhaler plus Tio 18 µg QD (morning) via a HandiHaler inhaler, in one of the three treatment periods. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. | 2 | 52 | 15 | 52 | ||
| EG001 | Tio 18 µg QD | Participants received Tio 18 µg QD (morning) via a HandiHaler inhaler plus Ado matching placebo BID (morning and evening) via dry powder inhaler, in one of the three treatment periods. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. | 0 | 51 | 8 | 51 | ||
| EG002 | Ado 50/250 µg BID | Participants received Ado 50/250 µg BID (morning and evening) via a dry powder inhaler plus Tio matching placebo QD (morning) via a HandiHaler inhaler, in one of the three treatment periods. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. | 0 | 51 | 11 | 51 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Prinzmetal angina | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Lumbar spinal stenosis | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lower respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pericoronitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Upper respiratory tract inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA | Systematic Assessment |
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GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068297 | Fluticasone-Salmeterol Drug Combination |
| D000069447 | Tiotropium Bromide |
| D000068298 | Fluticasone |
| D000068299 | Salmeterol Xinafoate |
| ID | Term |
|---|---|
| D000420 | Albuterol |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000730 | Androstadienes |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D012602 | Scopolamine Derivatives |
| D014326 | Tropanes |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
Not provided
Not provided
| AUC ratio |
| 1.288 |
| 2-Sided |
| 95 |
| 1.224 |
| 1.355 |
| Superiority or Other |
| OG002 | Ado 50/250 µg BID | Participants received Ado 50/250 µg BID (morning and evening) via a dry powder inhaler plus Tio matching placebo QD (morning) via a HandiHaler inhaler, in one of the three treatment periods. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. |
|
|
|
| OG002 | Ado 50/250 µg BID | Participants received Ado 50/250 µg BID (morning and evening) via a dry powder inhaler plus Tio matching placebo QD (morning) via a HandiHaler inhaler, in one of the three treatment periods. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. |
|
|
|
| OG002 | Ado 50/250 µg BID | Participants received Ado 50/250 µg BID (morning and evening) via a dry powder inhaler plus Tio matching placebo QD (morning) via a HandiHaler inhaler, in one of the three treatment periods. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. |
|
|
|
| OG001 | Tio 18 µg QD | Participants received Tio 18 µg QD (morning) via a HandiHaler inhaler plus Ado matching placebo BID (morning and evening) via dry powder inhaler, in one of the three treatment periods. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. |
| OG002 | Ado 50/250 µg BID | Participants received Ado 50/250 µg BID (morning and evening) via a dry powder inhaler plus Tio matching placebo QD (morning) via a HandiHaler inhaler, in one of the three treatment periods. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. |
|
|
|
| OG002 | Ado 50/250 µg BID | Participants received Ado 50/250 µg BID (morning and evening) via a dry powder inhaler plus Tio matching placebo QD (morning) via a HandiHaler inhaler, in one of the three treatment periods. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. |
|
|
|
Participants received Ado 50/250 µg BID (morning and evening) via a dry powder inhaler plus Tio matching placebo QD (morning) via a HandiHaler inhaler, in one of the three treatment periods. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. |
|
|
|
Participants received Ado 50/250 µg BID (morning and evening) via a dry powder inhaler plus Tio matching placebo QD (morning) via a HandiHaler inhaler, in one of the three treatment periods. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. |
|
|
|
Participants received Tio 18 µg QD (morning) via a HandiHaler inhaler plus Ado matching placebo BID (morning and evening) via dry powder inhaler, in one of the three treatment periods. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. |
| OG002 | Ado 50/250 µg BID | Participants received Ado 50/250 µg BID (morning and evening) via a dry powder inhaler plus Tio matching placebo QD (morning) via a HandiHaler inhaler, in one of the three treatment periods. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. |
|
|
|
| Ado 50/250 µg BID |
Participants received Ado 50/250 µg BID (morning and evening) via a dry powder inhaler plus Tio matching placebo QD (morning) via a HandiHaler inhaler, in one of the three treatment periods. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. |
|
|
|
| OG002 | Ado 50/250 µg BID | Participants received Ado 50/250 µg BID (morning and evening) via a dry powder inhaler plus Tio matching placebo QD (morning) via a HandiHaler inhaler, in one of the three treatment periods. Each treatment period consisted of 4 weeks and separated by a 2-week washout period. Participants were provided with a salbutamol inhaler to be used as relief medication throughout the study. |
|
|