Trial Outcomes & Findings for Fluticasone Propionate/Salmeterol Combination 250/50 DISKUS in the Exercise Endurance Time in Patients With Chronic Obstructive Pulmonary Disease (NCT NCT01124422)
NCT ID: NCT01124422
Last Updated: 2017-11-08
Results Overview
EET is defined as the time taken by a participant to exert himself during an exercise. EET was calculated based on the Endurance Shuttle Walk test (ESWT). The ESWT is a standardized, externally controlled, constant-paced field test for the assessment of endurance capacity in participants with chronic lung disease. Change from Baseline in EET was calculated as the value at Week 8 minus the value at Baseline.
COMPLETED
PHASE4
255 participants
Baseline (Week 3) and Week 8
2017-11-08
Participant Flow
In the open-label 4-week run-in phase, participants received 18 micrograms Tiotropium (TIO) once daily. Participants completing this phase (n=255) were then randomized to receive either TIO+placebo or TIO+Fluticasone propionate/salmeterol combination DISKUS. The number enrolled in the protocol section reflects these 255 randomized participants.
Participant milestones
| Measure |
Tiotropium (TIO)
Tiotropium (TIO) was administered in the dose of 18 micrograms (mcg) once daily for a duration of 4 weeks
|
TIO+Placebo
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|---|
|
4-Week Open-label Run-in Phase
STARTED
|
338
|
0
|
0
|
|
4-Week Open-label Run-in Phase
COMPLETED
|
255
|
0
|
0
|
|
4-Week Open-label Run-in Phase
NOT COMPLETED
|
83
|
0
|
0
|
|
4-Week Double-blind Treatment Phase
STARTED
|
0
|
131
|
124
|
|
4-Week Double-blind Treatment Phase
COMPLETED
|
0
|
120
|
115
|
|
4-Week Double-blind Treatment Phase
NOT COMPLETED
|
0
|
11
|
9
|
Reasons for withdrawal
| Measure |
Tiotropium (TIO)
Tiotropium (TIO) was administered in the dose of 18 micrograms (mcg) once daily for a duration of 4 weeks
|
TIO+Placebo
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|---|
|
4-Week Open-label Run-in Phase
Withdrawal by Subject
|
5
|
0
|
0
|
|
4-Week Open-label Run-in Phase
Adverse Event
|
7
|
0
|
0
|
|
4-Week Open-label Run-in Phase
Physician Decision
|
4
|
0
|
0
|
|
4-Week Open-label Run-in Phase
Lost to Follow-up
|
1
|
0
|
0
|
|
4-Week Open-label Run-in Phase
Did Not Meet Continuation Criteria
|
61
|
0
|
0
|
|
4-Week Open-label Run-in Phase
Protocol Violation
|
5
|
0
|
0
|
|
4-Week Double-blind Treatment Phase
Withdrawal by Subject
|
0
|
0
|
3
|
|
4-Week Double-blind Treatment Phase
Adverse Event
|
0
|
6
|
3
|
|
4-Week Double-blind Treatment Phase
Physician Decision
|
0
|
5
|
2
|
|
4-Week Double-blind Treatment Phase
Lost to Follow-up
|
0
|
0
|
1
|
Baseline Characteristics
Fluticasone Propionate/Salmeterol Combination 250/50 DISKUS in the Exercise Endurance Time in Patients With Chronic Obstructive Pulmonary Disease
Baseline characteristics by cohort
| Measure |
TIO+Placebo
n=131 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=124 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
Total
n=255 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.9 Years
STANDARD_DEVIATION 9.85 • n=5 Participants
|
62.5 Years
STANDARD_DEVIATION 8.94 • n=7 Participants
|
62.7 Years
STANDARD_DEVIATION 9.41 • n=5 Participants
|
|
Sex: Female, Male
Female
|
61 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
115 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
70 Participants
n=5 Participants
|
70 Participants
n=7 Participants
|
140 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
4 participants
n=5 Participants
|
10 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Japanese/East Asian Heritage/South East Asian
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or other Pacific Islander
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
126 participants
n=5 Participants
|
110 participants
n=7 Participants
|
236 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native and White
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Week 3) and Week 8Population: Intent-to-Treat (ITT) Population: all participants randomized to study drug. Only those participants contributing data at the indicated time points were analyzed.
EET is defined as the time taken by a participant to exert himself during an exercise. EET was calculated based on the Endurance Shuttle Walk test (ESWT). The ESWT is a standardized, externally controlled, constant-paced field test for the assessment of endurance capacity in participants with chronic lung disease. Change from Baseline in EET was calculated as the value at Week 8 minus the value at Baseline.
Outcome measures
| Measure |
TIO+Placebo
n=122 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=115 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in Exercise Endurance Time (EET) From Baseline (Week 3) to Week 8
|
23.3 Seconds (sec)
Standard Error 15.5
|
6.0 Seconds (sec)
Standard Error 16.2
|
SECONDARY outcome
Timeframe: Baseline (Week 3) and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
EDS is used to measure the level of breathlessness due to exercise, assessed using a 10-point modified Borg scale at 2-minute intervals during the ESWT: 0=no difficulty in breathing at all, 10=maximal breathing difficulty (BD). The participant pointed to the level on the scale correlating with his BD, and the local study coordinator confirmed that level verbally to him. Change from Baseline was calculated as the value at Week 8 minus the value at Baseline. A dyspnea score/time slope was calculated by fitting a linear regression line to the dyspnea scores reported during the exercise tests.
Outcome measures
| Measure |
TIO+Placebo
n=121 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=110 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in Scores on the Exercise Dyspnea Scale (EDS) From Baseline (Week 3) to Week 8
|
-0.1 Scores on a scale/minute
Standard Error 0.055
|
-0.06 Scores on a scale/minute
Standard Error 0.058
|
SECONDARY outcome
Timeframe: Baseline (Week 3) and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
EDS at isotime (last common time point for an exercise assessment \[i.e., last Borg score time point of the shortest exercise test for each participant\]) was assessed using a 10-point modified Borg scale. Change from Baseline in EDS at isotime was calculated as the value at Week 8 minus the value at Baseline.
Outcome measures
| Measure |
TIO+Placebo
n=121 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=110 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in EDS at Isotime From Baseline (Week 3) to Week 8
|
-0.3 Scores on a scale
Standard Error 0.2
|
-0.5 Scores on a scale
Standard Error 0.2
|
SECONDARY outcome
Timeframe: Baseline (Week 4) and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
Resting IC is the volume of gas that can be taken into the lungs in a full inhalation at the resting position. The resting IC was measured before and after dosing. Change from Baseline in pre-dose resting IC was calculated as the pre-dose value at Week 8 minus the pre-dose value at Week 4. Change from Baseline in post-dose resting IC was calculated as the post-dose value at Week 8 minus the pre-dose value at Week 4.
Outcome measures
| Measure |
TIO+Placebo
n=122 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=115 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in Pre-dose and Post-dose Resting Inspiratory Capacity (IC) From Baseline (Week 4) to Week 8
Pre-dose
|
-29 Milliliters (mL)
Standard Error 29
|
60 Milliliters (mL)
Standard Error 31.2
|
|
Mean Change in Pre-dose and Post-dose Resting Inspiratory Capacity (IC) From Baseline (Week 4) to Week 8
Post-dose
|
73 Milliliters (mL)
Standard Error 29.6
|
167 Milliliters (mL)
Standard Error 31.4
|
SECONDARY outcome
Timeframe: Baseline (Week 3) and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
EIC is the volume of gas that can be taken into the lungs in a full inhalation during exercise. Participants were asked to undergo the IC test every 2 minutes during exercise and at the end of the exercise, to follow changes in operational lung volumes that occured in association with exercise. Change from Baseline in EIC was calculated as the value at the end of exercise at Week 8 minus the value at the end of exercise at Baseline.
Outcome measures
| Measure |
TIO+Placebo
n=38 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=29 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in Exercise Inspiratory Capacity (EIC) at the End of Exercise From Baseline (Week 3) to Week 8
|
-7.4 mL
Standard Error 120
|
46.6 mL
Standard Error 93.3
|
SECONDARY outcome
Timeframe: Baseline (Week 3) and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
The V'O2 was measured during the ESWT using the Oxycon Mobile System (OMS), a portable telemetric monitoring system consisting of an oxygen sensor allowing for breath-by-breath measurement of gas exchange parameters in the lungs. The V'O2 was collected in units of mL and then regressed over the conduct of the exercise test measured in minutes. The V'O2 per time slope was calculated for each participant (par.) by fitting a linear regression line to the V'O2 recorded for each par. during the ESWT. V'O2 per time slope results were compared between treatment groups as means of these regression lin
Outcome measures
| Measure |
TIO+Placebo
n=41 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=32 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in Flow of Oxygen (V'O2) Per Time Slope During the Course of the ESWT From Baseline (Week 3) to Week 8
|
-13.3 mL/minute (min)
Standard Error 10.36
|
-6.1 mL/minute (min)
Standard Error 14.89
|
SECONDARY outcome
Timeframe: Baseline (Week 3) and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
The amount of CO2 in the hemoglobin of the participants was measured during the ESWT using the OMS. The system consisted of a carbon dioxide sensor and allowed breath-by-breath measurement of pulmonary gas exchange parameters. The V'CO2 per time slope was calculated for each participant by fitting a linear regression line to the V'CO2 recorded for each participant during the ESWT. V'CO2 per time slope results were compared between treatment groups as means of these regression lines. Change from Baseline in V'CO2 per time slope was calculated as the value at Week 8 minus the value at Baseline.
Outcome measures
| Measure |
TIO+Placebo
n=41 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=31 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in Flow of Carbon Dioxide (V'CO2) Per Time Slope During the Course of the ESWT From Baseline (Week 3) to Week 8
|
-17.4 mL/min
Standard Error 10.36
|
-0.7 mL/min
Standard Error 11.96
|
SECONDARY outcome
Timeframe: Baseline (Week 3) and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
The V'E was measured in the participants during the ESWT using the OMS. The system consisted of a volume transducer, oxygen sensor, and carbon dioxide sensor and allowed breath-by-breath measurement of pulmonary gas exchange parameters. The V'E was collected in liters and then regressed over the conduct of the exercise test measured in minutes. The V'E per time slope was calculated for each participant by fitting a linear regression line to the V'E recorded for each participant during the ESWT. V'E per time slope results were compared between treatment groups as means of the regression lines.
Outcome measures
| Measure |
TIO+Placebo
n=42 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=34 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in Minute Ventilation (V'E) Per Time Slope During the Course of the ESWT From Baseline (Week 3) to Week 8
|
-0.7 Liter (L)/min
Standard Error 0.35
|
-0.2 Liter (L)/min
Standard Error 0.49
|
SECONDARY outcome
Timeframe: Baseline (Week 3) and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
HR is defined as the number of heartbeats per unit of time, typically expressed as beats per minute (bpm). It was measured during the ESWT using the OMS. The HR was collected in units of bpm and then regressed over the conduct of the exercise test measured in minutes. The HR per time slope was calculated for each participant by fitting a linear regression line to the HR recorded for each participant during the exercise test. HR per time slope results were compared between treatment groups as means of these regression lines.
Outcome measures
| Measure |
TIO+Placebo
n=42 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=34 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in Heart Rate (HR) Per Time Slope During the Course of the ESWT From Baseline (Week 3) to Week 8
|
-1.1 bpm/min
Standard Error 0.70
|
0.7 bpm/min
Standard Error 0.80
|
SECONDARY outcome
Timeframe: Baseline (Week 3) and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
The respiratory exchange ratio was calculated as the ratio of VCO2 and VO2. The ratio of the amount of carbon dioxide and oxygen in the hemoglobin of the participants was measured during the ESWT using the OMS. The system consisted of oxygen and carbon dioxide sensors and allowed breath-by-breath measurement of pulmonary gas exchange parameters. Change from Baseline in RER was calculated as the value at Week 8 minus the value at Baseline.
Outcome measures
| Measure |
TIO+Placebo
n=42 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=34 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in Respiratory Exchange Ratio (RER) Per Time Slope During the Course of the ESWT From Baseline to Week 8
|
-0.01 Ratio of VCO2 and VO2
Standard Error 0.004
|
0.01 Ratio of VCO2 and VO2
Standard Error 0.007
|
SECONDARY outcome
Timeframe: Baseline (Week 3) and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
RR is defined as the number of breaths taken within a set amount of time (typically within 60 secs). The RR of the participants was measured during the ESWT using the OMS. The system consisted of volume transducer oxygen and carbon dioxide sensors and allowed breath-by-breath measurement of pulmonary gas exchange parameters. The RR per time slope was calculated for each participant by fitting a linear regression line to the RR recorded for each participant during the ESWT. RR per time slope results were compared between treatment groups as means of these regression lines.
Outcome measures
| Measure |
TIO+Placebo
n=42 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=34 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in Respiratory Rate (RR) Per Time Slope During the Course of the ESWT From Baseline (Week 3) to Week 8
|
-0.1 breaths/min/min
Standard Error 0.18
|
-0.5 breaths/min/min
Standard Error 0.44
|
SECONDARY outcome
Timeframe: Baseline (Week 3) and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
RR is defined as the number of breaths taken within a set amount of time (typically within 60 secs). The RR of the participants at isotime was measured during the ESWT using the OMS. Change from Baseline in RR at isotime was calculated as the value at Week 8 minus the value at Baseline.
Outcome measures
| Measure |
TIO+Placebo
n=42 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=34 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in Respiratory Rate (RR) at Isotime During the Course of the ESWT From Baseline to Week 8
|
0.8 breaths/min
Standard Error 0.71
|
-0.5 breaths/min
Standard Error 0.68
|
SECONDARY outcome
Timeframe: Baseline (Week 3) and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
VT is the lung volume representing the normal volume of air displaced between normal inspiration and expiration when extra effort is not applied (normal value is approximately 500 mL or 7 mL/kg body weight). VT was measured during the ESWT using the OMS, consisting of volume transducer O2 and CO2 sensors and allowing breath-by-breath measurement of pulmonary gas exchange parameters. The participant's VT per time slope was calculated by fitting a linear regression line (RL) to their VT during the ESWT. VT per time slope results were compared between treatment groups as means of these RLs.
Outcome measures
| Measure |
TIO+Placebo
n=42 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=34 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in Tidal Volume (VT) Per Time Slope During the Course of the ESWT From Baseline to Week 8
|
-0.02 L/min
Standard Error 0.008
|
0 L/min
Standard Error 0.014
|
SECONDARY outcome
Timeframe: Baseline (Week 3) and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
VT is defined as the lung volume representing the normal volume of air displaced between normal inspiration and expiration when extra effort is not applied. The normal value is approximately 500 mL or 7 mL/kg body weight. The VT of the participants at isotime was measured during the ESWT using the OMS. Change from Baseline in VT at isotime was calculated as the value at Week 8 minus the value at Baseline.
Outcome measures
| Measure |
TIO+Placebo
n=42 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=34 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in Tidal Volume (VT) at Isotime During the Course of the ESWT From Baseline to Week 8
|
-0.10 L
Standard Error 0.04
|
0.08 L
Standard Error 0.042
|
SECONDARY outcome
Timeframe: Baseline (Week 3) and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed. A subgroup of participants specified sites provided cardio-respiratory and exercise IC measurements with the Oxycon Mobile System (OMS). Participants not at these sites formed the non-OMS subgroup.
HR was measured during the course of the ESWT in the non-OMS subgroup using pulse oximetry. The HR per time slope was calculated for each participant by fitting a linear regression line to the HR recorded for each participant during the ESWT. HR per time slope results were compared between treatment groups as means of these regression lines. Change from Baseline in HR was calculated as the value at Week 8 minus the value at Baseline.
Outcome measures
| Measure |
TIO+Placebo
n=72 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=76 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in HR Per Time Slope During the Course of the ESWT Using Pulse Oximetry From Baseline to Week 8 (Non-OMS Subgroup)
|
-0.8 bpm/min
Standard Error 0.55
|
-0.6 bpm/min
Standard Error 0.56
|
SECONDARY outcome
Timeframe: Baseline (Week 3) and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
The RR and VT of the participants at isotime were measured during the ESWT using the OMS. The ratio of RR per VT (value of RR divided by value of VT) at isotime was calculated. Change from Baseline in RR/VT at isotime was calculated as the value at Week 8 minus the value at Baseline.
Outcome measures
| Measure |
TIO+Placebo
n=42 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=34 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in Ratio of Respiratory Rate (RR) to Tidal Volume (VT) or RR/VT at Isotime During the Course of the ESWT From Baseline to Week 8
|
2.7 breaths/min/L
Standard Error 1.14
|
-2.5 breaths/min/L
Standard Error 1.27
|
SECONDARY outcome
Timeframe: Baseline (Week 3) and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
The EIC was measured at 2 to 3.5 minutes during the exercise period. Change from Baseline in EIC was calculated as the value at Week 8 minus the value at Baseline.
Outcome measures
| Measure |
TIO+Placebo
n=24 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=22 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in EIC at 2 to 3.5 Minutes During the Exercise Period From Baseline (Week 3) to Week 8
|
-148.3 mL
Standard Error 118.7
|
200 mL
Standard Error 110.2
|
SECONDARY outcome
Timeframe: Week 4 and Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
The CRQ-SAS, a self-administered tool used to assess health-related quality-of-life (HRQOL), consists of 20 questions (q.) in 4 domains: Dyspnea (5 q.), Fatigue (4 q.), Emotional Function (7 q.), and Mastery (4 q.). Participants rated their experience on a 7-point scale in response to each q.: 1 (maximum impairment) to 7 (no impairment); higher scores indicate better HRQOL. Individual q. were equally weighted, and domain scores (range=1-7) were calculated as the mean across the non-missing items within each domain (domain scores were calculated although an individual item score was missing).
Outcome measures
| Measure |
TIO+Placebo
n=122 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=115 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Mean Change in Scores on the Chronic Respiratory Disease Questionnaire Self-Administered Standardized (CRQ-SAS) Questionnaire From Week 4 to Week 8
Mastery Score
|
0.07 Scores on a scale
Standard Error 0.08
|
0.09 Scores on a scale
Standard Error 0.1
|
|
Mean Change in Scores on the Chronic Respiratory Disease Questionnaire Self-Administered Standardized (CRQ-SAS) Questionnaire From Week 4 to Week 8
Dyspnea Score
|
0.21 Scores on a scale
Standard Error 0.09
|
0.32 Scores on a scale
Standard Error 0.1
|
|
Mean Change in Scores on the Chronic Respiratory Disease Questionnaire Self-Administered Standardized (CRQ-SAS) Questionnaire From Week 4 to Week 8
Fatigue Score
|
0.11 Scores on a scale
Standard Error 0.08
|
0.26 Scores on a scale
Standard Error 0.1
|
|
Mean Change in Scores on the Chronic Respiratory Disease Questionnaire Self-Administered Standardized (CRQ-SAS) Questionnaire From Week 4 to Week 8
Emotional Function Score
|
0.10 Scores on a scale
Standard Error 0.07
|
0.13 Scores on a scale
Standard Error 0.08
|
SECONDARY outcome
Timeframe: BDI: Week 4; TDI: Week 8Population: ITT Population. Only those participants contributing data at the indicated time points were analyzed.
The BDI-TDI is a multidimensional dyspnea measurement. The BDI, administered at Week 4, consisted of 3 items (functional impairment, magnitude of task in exertional capacity, and magnitude of effort) requiring recall over the previous 4 weeks. BDI scores ranged from 0 (very severe impairment) to 4 (no impairment); the summed total score = 0 to 12. The TDI, administered at Week 8 as a follow-up of the BDI, consisted of the same 3 items requiring recall over the previous 4 weeks. TDI scores ranged from -3 (major deterioration) to +3 (major improvement); the summed total score = -9 to 9.
Outcome measures
| Measure |
TIO+Placebo
n=130 Participants
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=122 Participants
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Baseline Dyspnea Index (BDI) at Week 4 and Transition Dyspnea Index (TDI) at Week 8
BDI; n=130; 122
|
6.7 Scores on a scale
Standard Error 0.20
|
6.9 Scores on a scale
Standard Error 0.22
|
|
Baseline Dyspnea Index (BDI) at Week 4 and Transition Dyspnea Index (TDI) at Week 8
TDI; n=121, 115
|
1.1 Scores on a scale
Standard Error 0.2
|
1.4 Scores on a scale
Standard Error 0.2
|
Adverse Events
TIO+Placebo
TIO+FSC
Serious adverse events
| Measure |
TIO+Placebo
n=131 participants at risk
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=124 participants at risk
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.5%
2/131
|
0.00%
0/124
|
|
Cardiac disorders
Acute myocardial infarction
|
0.76%
1/131
|
0.00%
0/124
|
Other adverse events
| Measure |
TIO+Placebo
n=131 participants at risk
Matching placebo DISKUS twice daily (BD) plus tiotropium 18 mcg once daily for a duration of 4 weeks
|
TIO+FSC
n=124 participants at risk
Fluticasone propionate/salmeterol combination (FSC) DISKUS, administered in the dose of 250/50 mcg BD, plus tiotropium in the dose of 18 mcg once daily for a duration of 4 weeks
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
2.3%
3/131
|
0.81%
1/124
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.76%
1/131
|
1.6%
2/124
|
|
Respiratory, thoracic and mediastinal disorders
Dsyphonia
|
0.00%
0/131
|
1.6%
2/124
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.76%
1/131
|
0.81%
1/124
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.76%
1/131
|
0.00%
0/124
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/131
|
0.81%
1/124
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
0.00%
0/131
|
0.81%
1/124
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.5%
2/131
|
0.81%
1/124
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/131
|
2.4%
3/124
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.76%
1/131
|
0.00%
0/124
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.76%
1/131
|
0.00%
0/124
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/131
|
0.81%
1/124
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/131
|
0.81%
1/124
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/131
|
2.4%
3/124
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/131
|
1.6%
2/124
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/131
|
0.81%
1/124
|
|
Gastrointestinal disorders
Chapped lips
|
0.76%
1/131
|
0.00%
0/124
|
|
Gastrointestinal disorders
Diarrhoea
|
0.76%
1/131
|
0.00%
0/124
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.76%
1/131
|
0.00%
0/124
|
|
Infections and infestations
Nasopharyngitis
|
0.76%
1/131
|
1.6%
2/124
|
|
Infections and infestations
Bronchitis
|
0.00%
0/131
|
1.6%
2/124
|
|
Infections and infestations
Acute sinusitis
|
0.00%
0/131
|
0.81%
1/124
|
|
Infections and infestations
Cellulitis
|
0.00%
0/131
|
0.81%
1/124
|
|
Infections and infestations
Labyrinthitis
|
0.00%
0/131
|
0.81%
1/124
|
|
Infections and infestations
Oral herpes
|
0.76%
1/131
|
0.00%
0/124
|
|
Injury, poisoning and procedural complications
Contusion
|
0.76%
1/131
|
0.81%
1/124
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/131
|
0.81%
1/124
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.76%
1/131
|
0.00%
0/124
|
|
Injury, poisoning and procedural complications
Joint injury
|
0.76%
1/131
|
0.00%
0/124
|
|
Injury, poisoning and procedural complications
Skeletal injury
|
0.76%
1/131
|
0.00%
0/124
|
|
Injury, poisoning and procedural complications
Soft tissue injury
|
0.76%
1/131
|
0.00%
0/124
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/131
|
0.81%
1/124
|
|
Cardiac disorders
Coronary artery disease
|
0.76%
1/131
|
0.00%
0/124
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/131
|
0.81%
1/124
|
|
Eye disorders
Eye pain
|
0.76%
1/131
|
0.00%
0/124
|
|
Psychiatric disorders
Depression
|
0.00%
0/131
|
0.81%
1/124
|
|
Psychiatric disorders
Insomnia
|
0.76%
1/131
|
0.00%
0/124
|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
0.76%
1/131
|
0.00%
0/124
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/131
|
0.81%
1/124
|
|
General disorders
Chest discomfort
|
0.76%
1/131
|
0.00%
0/124
|
|
Metabolism and nutrition disorders
Hyperlipidemia
|
0.76%
1/131
|
0.00%
0/124
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.76%
1/131
|
0.00%
0/124
|
|
Nervous system disorders
Migraine
|
0.00%
0/131
|
0.81%
1/124
|
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER