Trial Outcomes & Findings for A 3 Way Cross-over Study Evaluating the Effects of ADOAIR Twice Daily Plus Tiotropium Bromide Once Daily Compared With the Individual Treatments of Japanese Subjects (NCT NCT01751113)
NCT ID: NCT01751113
Last Updated: 2017-03-08
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
53 participants
Primary outcome timeframe
Day 28 of each treatment period (up to 35 days)
Results posted on
2017-03-08
Participant Flow
A total of 53 Japanese participants with moderate or severe chronic obstructive pulmonary disease (COPD) entered the run-in period.
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.
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Treatment Period 1 (4 Weeks)
STARTED
|
8
|
8
|
9
|
9
|
9
|
10
|
|
Treatment Period 1 (4 Weeks)
COMPLETED
|
8
|
8
|
9
|
8
|
8
|
10
|
|
Treatment Period 1 (4 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
1
|
1
|
0
|
|
Washout Period 1 (2 Weeks)
STARTED
|
8
|
8
|
9
|
8
|
8
|
10
|
|
Washout Period 1 (2 Weeks)
COMPLETED
|
8
|
8
|
9
|
8
|
8
|
10
|
|
Washout Period 1 (2 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 2 (4 Weeks)
STARTED
|
8
|
8
|
9
|
8
|
8
|
10
|
|
Treatment Period 2 (4 Weeks)
COMPLETED
|
8
|
8
|
9
|
8
|
8
|
10
|
|
Treatment Period 2 (4 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period 2 (2 Weeks)
STARTED
|
8
|
8
|
9
|
8
|
8
|
10
|
|
Washout Period 2 (2 Weeks)
COMPLETED
|
8
|
8
|
9
|
8
|
8
|
10
|
|
Washout Period 2 (2 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 3 (4 Weeks)
STARTED
|
8
|
8
|
9
|
8
|
8
|
10
|
|
Treatment Period 3 (4 Weeks)
COMPLETED
|
8
|
8
|
9
|
8
|
8
|
9
|
|
Treatment Period 3 (4 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Treatment Period 1 (4 Weeks)
Adverse Event
|
0
|
0
|
0
|
1
|
1
|
0
|
|
Treatment Period 3 (4 Weeks)
Adverse Event
|
0
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
A 3 Way Cross-over Study Evaluating the Effects of ADOAIR Twice Daily Plus Tiotropium Bromide Once Daily Compared With the Individual Treatments of Japanese Subjects
Baseline characteristics by cohort
| Measure |
Ado 50/250 µg+Tio 18 µg, Ado 50/250 µg, Tio 18 µg
n=53 Participants
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.
|
|---|---|
|
Age, Continuous
|
67.2 Years
STANDARD_DEVIATION 6.56 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
52 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian - Japanese Heritage
|
53 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 28 of each treatment period (up to 35 days)Population: 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.
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.
Outcome measures
| Measure |
Ado 50/250 µg BID+Tio 18 µg QD
n=50 Participants
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.
|
Tio 18 µg QD
n=50 Participants
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.
|
Ado 50/250 µg BID
n=50 Participants
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.
|
|---|---|---|---|
|
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
|
0.854 1/kilopascal*second (1/kPa*s)
Standard Error 0.0183
|
0.737 1/kilopascal*second (1/kPa*s)
Standard Error 0.0183
|
0.663 1/kilopascal*second (1/kPa*s)
Standard Error 0.0182
|
SECONDARY outcome
Timeframe: Day 28 of each treatment period (up to 35 days)Population: mITT Population
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.
Outcome measures
| Measure |
Ado 50/250 µg BID+Tio 18 µg QD
n=50 Participants
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.
|
Tio 18 µg QD
n=50 Participants
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.
|
Ado 50/250 µg BID
n=50 Participants
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.
|
|---|---|---|---|
|
AUC (0-4hr) Specific Airway Resistance (sRaw) After the Morning Dose of Each Study Medication at Day 28 of Each Treatment Period
|
1.181 kPa*s
Standard Error 0.0188
|
1.380 kPa*s
Standard Error 0.0189
|
1.525 kPa*s
Standard Error 0.0188
|
SECONDARY outcome
Timeframe: Day 28 of each treatment period (up to 35 days)Population: mITT Population
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.
Outcome measures
| Measure |
Ado 50/250 µg BID+Tio 18 µg QD
n=50 Participants
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.
|
Tio 18 µg QD
n=50 Participants
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.
|
Ado 50/250 µg BID
n=50 Participants
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.
|
|---|---|---|---|
|
Post-dose sGaw at 30, 75, 120 and 240 Minutes Post Dose at Day 28 of Each Treatment Period
30 min
|
0.833 1/kPa*s
Standard Error 0.0241
|
0.705 1/kPa*s
Standard Error 0.0241
|
0.639 1/kPa*s
Standard Error 0.0240
|
|
Post-dose sGaw at 30, 75, 120 and 240 Minutes Post Dose at Day 28 of Each Treatment Period
75 min
|
0.873 1/kPa*s
Standard Error 0.0241
|
0.743 1/kPa*s
Standard Error 0.0241
|
0.652 1/kPa*s
Standard Error 0.0240
|
|
Post-dose sGaw at 30, 75, 120 and 240 Minutes Post Dose at Day 28 of Each Treatment Period
120 min
|
0.885 1/kPa*s
Standard Error 0.0241
|
0.769 1/kPa*s
Standard Error 0.0241
|
0.680 1/kPa*s
Standard Error 0.0240
|
|
Post-dose sGaw at 30, 75, 120 and 240 Minutes Post Dose at Day 28 of Each Treatment Period
240 min
|
0.855 1/kPa*s
Standard Error 0.0241
|
0.750 1/kPa*s
Standard Error 0.0241
|
0.690 1/kPa*s
Standard Error 0.0240
|
SECONDARY outcome
Timeframe: Day 28 of each treatment period (up to 35 days)Population: mITT Population
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.
Outcome measures
| Measure |
Ado 50/250 µg BID+Tio 18 µg QD
n=50 Participants
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.
|
Tio 18 µg QD
n=50 Participants
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.
|
Ado 50/250 µg BID
n=50 Participants
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.
|
|---|---|---|---|
|
Post-dose sRaw at 30, 75, 120 and 240 Minutes Post Dose at Day 28 of Each Treatment Period
75 min
|
1.146 kPa*s
Standard Error 0.0240
|
1.348 kPa*s
Standard Error 0.0240
|
1.535 kPa*s
Standard Error 0.0240
|
|
Post-dose sRaw at 30, 75, 120 and 240 Minutes Post Dose at Day 28 of Each Treatment Period
120 min
|
1.129 kPa*s
Standard Error 0.0240
|
1.300 kPa*s
Standard Error 0.0240
|
1.468 kPa*s
Standard Error 0.0240
|
|
Post-dose sRaw at 30, 75, 120 and 240 Minutes Post Dose at Day 28 of Each Treatment Period
240 min
|
1.170 kPa*s
Standard Error 0.0240
|
1.334 kPa*s
Standard Error 0.0240
|
1.446 kPa*s
Standard Error 0.0240
|
|
Post-dose sRaw at 30, 75, 120 and 240 Minutes Post Dose at Day 28 of Each Treatment Period
30 min
|
1.201 kPa*s
Standard Error 0.0240
|
1.419 kPa*s
Standard Error 0.0240
|
1.567 kPa*s
Standard Error 0.0240
|
SECONDARY outcome
Timeframe: Day 28 of each treatment period (up to 35 days)Population: mITT Population
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.
Outcome measures
| Measure |
Ado 50/250 µg BID+Tio 18 µg QD
n=50 Participants
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.
|
Tio 18 µg QD
n=50 Participants
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.
|
Ado 50/250 µg BID
n=50 Participants
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.
|
|---|---|---|---|
|
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
|
1.823 Liters (L)
Standard Error 0.0147
|
1.666 Liters (L)
Standard Error 0.0147
|
1.706 Liters (L)
Standard Error 0.0147
|
|
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
FVC
|
3.575 Liters (L)
Standard Error 0.0182
|
3.493 Liters (L)
Standard Error 0.0182
|
3.439 Liters (L)
Standard Error 0.0182
|
|
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
IC
|
2.460 Liters (L)
Standard Error 0.0177
|
2.406 Liters (L)
Standard Error 0.0179
|
2.395 Liters (L)
Standard Error 0.0174
|
|
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
RV
|
3.021 Liters (L)
Standard Error 0.0282
|
3.129 Liters (L)
Standard Error 0.0286
|
3.123 Liters (L)
Standard Error 0.0278
|
|
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
TLC
|
6.511 Liters (L)
Standard Error 0.0189
|
6.524 Liters (L)
Standard Error 0.0191
|
6.525 Liters (L)
Standard Error 0.0186
|
|
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
TGV
|
4.053 Liters (L)
Standard Error 0.0206
|
4.118 Liters (L)
Standard Error 0.0210
|
4.129 Liters (L)
Standard Error 0.0204
|
SECONDARY outcome
Timeframe: Day 28 of each treatment period (up to 35 days)Population: mITT Population
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.
Outcome measures
| Measure |
Ado 50/250 µg BID+Tio 18 µg QD
n=50 Participants
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.
|
Tio 18 µg QD
n=50 Participants
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.
|
Ado 50/250 µg BID
n=50 Participants
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.
|
|---|---|---|---|
|
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
|
0.513 Ratio of FEV1/FVC
Standard Error 0.0032
|
0.481 Ratio of FEV1/FVC
Standard Error 0.0032
|
0.496 Ratio of FEV1/FVC
Standard Error 0.0032
|
SECONDARY outcome
Timeframe: Day 28 of each treatment period (up to 35 days)Population: mITT Population
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.
Outcome measures
| Measure |
Ado 50/250 µg BID+Tio 18 µg QD
n=50 Participants
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.
|
Tio 18 µg QD
n=50 Participants
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.
|
Ado 50/250 µg BID
n=50 Participants
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.
|
|---|---|---|---|
|
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
|
1.391 kPa*s
Standard Error 0.0288
|
1.666 kPa*s
Standard Error 0.0286
|
1.732 kPa*s
Standard Error 0.0284
|
SECONDARY outcome
Timeframe: Day 28 of each treatment period (up to 35 days)Population: mITT Population
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.
Outcome measures
| Measure |
Ado 50/250 µg BID+Tio 18 µg QD
n=50 Participants
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.
|
Tio 18 µg QD
n=50 Participants
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.
|
Ado 50/250 µg BID
n=50 Participants
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.
|
|---|---|---|---|
|
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
|
0.720 1/kPa*s
Standard Error 0.0287
|
0.600 1/kPa*s
Standard Error 0.0285
|
0.577 1/kPa*s
Standard Error 0.0284
|
SECONDARY outcome
Timeframe: Day 28 of each treatment period (up to 35 days)Population: mITT Population
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.
Outcome measures
| Measure |
Ado 50/250 µg BID+Tio 18 µg QD
n=50 Participants
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.
|
Tio 18 µg QD
n=50 Participants
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.
|
Ado 50/250 µg BID
n=50 Participants
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.
|
|---|---|---|---|
|
Post-dose FEV1, FVC, IC, RV, TLC and TGV (Measured at Trough) at Day 28 of Each Treatment Period
RV
|
3.045 Liters (L)
Standard Error 0.0543
|
3.275 Liters (L)
Standard Error 0.0542
|
3.234 Liters (L)
Standard Error 0.0533
|
|
Post-dose FEV1, FVC, IC, RV, TLC and TGV (Measured at Trough) at Day 28 of Each Treatment Period
TLC
|
6.487 Liters (L)
Standard Error 0.0395
|
6.588 Liters (L)
Standard Error 0.0394
|
6.592 Liters (L)
Standard Error 0.0386
|
|
Post-dose FEV1, FVC, IC, RV, TLC and TGV (Measured at Trough) at Day 28 of Each Treatment Period
TGV
|
4.147 Liters (L)
Standard Error 0.0414
|
4.239 Liters (L)
Standard Error 0.0414
|
4.238 Liters (L)
Standard Error 0.0405
|
|
Post-dose FEV1, FVC, IC, RV, TLC and TGV (Measured at Trough) at Day 28 of Each Treatment Period
FEV1
|
1.766 Liters (L)
Standard Error 0.0269
|
1.605 Liters (L)
Standard Error 0.0269
|
1.664 Liters (L)
Standard Error 0.0269
|
|
Post-dose FEV1, FVC, IC, RV, TLC and TGV (Measured at Trough) at Day 28 of Each Treatment Period
FVC
|
3.535 Liters (L)
Standard Error 0.0403
|
3.430 Liters (L)
Standard Error 0.0403
|
3.387 Liters (L)
Standard Error 0.0403
|
|
Post-dose FEV1, FVC, IC, RV, TLC and TGV (Measured at Trough) at Day 28 of Each Treatment Period
IC
|
2.344 Liters (L)
Standard Error 0.0415
|
2.351 Liters (L)
Standard Error 0.0414
|
2.351 Liters (L)
Standard Error 0.0405
|
SECONDARY outcome
Timeframe: Day 28 of each treatment period (up to 35 days)Population: mITT Population
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.
Outcome measures
| Measure |
Ado 50/250 µg BID+Tio 18 µg QD
n=50 Participants
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.
|
Tio 18 µg QD
n=50 Participants
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.
|
Ado 50/250 µg BID
n=50 Participants
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.
|
|---|---|---|---|
|
Post-dose FEV1/FVC Ratio (Measured at Trough) at Day 28 of Each Treatment Period
|
0.500 Ratio of FEV1/FVC
Standard Error 0.0052
|
0.472 Ratio of FEV1/FVC
Standard Error 0.0052
|
0.492 Ratio of FEV1/FVC
Standard Error 0.0052
|
SECONDARY outcome
Timeframe: Day 28 of each treatment period (up to 35 days)Population: 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).
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.
Outcome measures
| Measure |
Ado 50/250 µg BID+Tio 18 µg QD
n=50 Participants
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.
|
Tio 18 µg QD
n=50 Participants
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.
|
Ado 50/250 µg BID
n=50 Participants
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.
|
|---|---|---|---|
|
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
Treatment, n=20, 18, 17
|
0.2 Number of occasions
Standard Deviation 0.62
|
0.3 Number of occasions
Standard Deviation 0.82
|
0.2 Number of occasions
Standard Deviation 0.55
|
|
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
Washout, n=15, 15, 11
|
0.4 Number of occasions
Standard Deviation 0.81
|
0.5 Number of occasions
Standard Deviation 1.24
|
0.4 Number of occasions
Standard Deviation 1.01
|
Adverse Events
Ado 50/250 µg BID+Tio 18 µg QD
Serious events: 2 serious events
Other events: 15 other events
Deaths: 0 deaths
Tio 18 µg QD
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Ado 50/250 µg BID
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ado 50/250 µg BID+Tio 18 µg QD
n=52 participants at risk
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.
|
Tio 18 µg QD
n=51 participants at risk
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.
|
Ado 50/250 µg BID
n=51 participants at risk
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.
|
|---|---|---|---|
|
Cardiac disorders
Prinzmetal angina
|
1.9%
1/52 • 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.
|
0.00%
0/51 • 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.
|
0.00%
0/51 • 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.
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
1.9%
1/52 • 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.
|
0.00%
0/51 • 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.
|
0.00%
0/51 • 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.
|
Other adverse events
| Measure |
Ado 50/250 µg BID+Tio 18 µg QD
n=52 participants at risk
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.
|
Tio 18 µg QD
n=51 participants at risk
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.
|
Ado 50/250 µg BID
n=51 participants at risk
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.
|
|---|---|---|---|
|
Infections and infestations
Lower respiratory tract infection
|
1.9%
1/52 • 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.
|
0.00%
0/51 • 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.
|
0.00%
0/51 • 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.
|
|
Infections and infestations
Nasopharyngitis
|
5.8%
3/52 • 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.
|
2.0%
1/51 • 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.
|
2.0%
1/51 • 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.
|
|
Infections and infestations
Pericoronitis
|
1.9%
1/52 • 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.
|
0.00%
0/51 • 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.
|
0.00%
0/51 • 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.
|
|
Nervous system disorders
Headache
|
0.00%
0/52 • 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.
|
2.0%
1/51 • 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.
|
0.00%
0/51 • 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.
|
|
Vascular disorders
Hypertension
|
0.00%
0/52 • 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.
|
2.0%
1/51 • 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.
|
0.00%
0/51 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.9%
1/52 • 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.
|
0.00%
0/51 • 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.
|
0.00%
0/51 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
9.6%
5/52 • 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.
|
2.0%
1/51 • 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.
|
5.9%
3/51 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/52 • 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.
|
2.0%
1/51 • 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.
|
0.00%
0/51 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/52 • 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.
|
0.00%
0/51 • 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.
|
2.0%
1/51 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
0.00%
0/52 • 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.
|
0.00%
0/51 • 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.
|
2.0%
1/51 • 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.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/52 • 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.
|
0.00%
0/51 • 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.
|
2.0%
1/51 • 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.
|
|
Gastrointestinal disorders
Dry mouth
|
1.9%
1/52 • 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.
|
2.0%
1/51 • 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.
|
2.0%
1/51 • 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.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/52 • 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.
|
2.0%
1/51 • 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.
|
0.00%
0/51 • 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.
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.9%
1/52 • 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.
|
0.00%
0/51 • 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.
|
0.00%
0/51 • 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.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.8%
2/52 • 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.
|
0.00%
0/51 • 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.
|
0.00%
0/51 • 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.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/52 • 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.
|
2.0%
1/51 • 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.
|
2.0%
1/51 • 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.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/52 • 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.
|
0.00%
0/51 • 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.
|
2.0%
1/51 • 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.
|
|
General disorders
Oedema peripheral
|
0.00%
0/52 • 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.
|
0.00%
0/51 • 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.
|
2.0%
1/51 • 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.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
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