Trial Outcomes & Findings for Safety Study Using GSK573719 And Tiotropium In Patients With Chronic Obstructive Pulmonary Disease (NCT NCT00515502)
NCT ID: NCT00515502
Last Updated: 2017-08-22
Results Overview
Resting heart rate was measured at pre-dose and 15 minutes (min), 45min, 1.5 hour (h) 4 h, 8 h, and 24 h post-dose of each treatment period and the maximum value for heart rate (0-4hours) was derived at rest. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
24 participants
Primary outcome timeframe
Day 1 of each treatment period (up to Study Day 46)
Results posted on
2017-08-22
Participant Flow
Participants were randomized to receive a sequence of 4 of 5 possible treatments over 4 treatment periods each separated by a washout period of at least 14 days. Participants were randomized to receive treatments in 12 possible sequences.
Participant milestones
| Measure |
Seq 1: UMEC 250 µg, UMEC 500 µg, Tiotropium 18 µg, Placebo
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: umeclidinium bromide (UMEC) 250 micrograms (µg), UMEC 500 µg, Tiotropium 18 µg and placebo. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 2: UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg, Placebo
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg and placebo. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 3: UMEC 250 µg, Placebo, UMEC 500 µg, UMEC 1000 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, placebo, UMEC 500 µg and UMEC 1000 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 4: UMEC 250 µg, UMEC 500 µg, Placebo, UMEC 1000 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, UMEC 500 µg, placebo and UMEC 1000 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 5: Placebo, UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Placebo, UMEC 250 µg, UMEC 500 µg and UMEC 1000 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 6: UMEC 250 µg, Placebo, Tiotropium 18 µg, UMEC 500 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, placebo, Tiotropium 18 µg and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 7: Placebo, Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Placebo, Tiotropium 18 µg, UMEC 250 µg and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 8: Tiotropium 18 µg, Placebo, UMEC 250 µg, UMEC 500 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Tiotropium 18 µg, placebo, UMEC 250 µg and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 9: Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg, Placebo
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg and placebo. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 10: Tiotropium 18 µg, UMEC 250 µg, Placebo, UMEC 500 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Tiotropium 18 µg, UMEC 250 µg, placebo and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 11: Placebo, UMEC 250 µg, Tiotropium 18 µg, UMEC 500 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Placebo, UMEC 250 µg, Tiotropium 18 µg and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 12: UMEC 250 µg, Placebo, UMEC 500 µg, Tiotropium 18 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, placebo, UMEC 500 µg and Tiotropium 18 µg. Treatment periods were seperated by a washout period of at least 14 days.
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Treatment Period 1
STARTED
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Treatment Period 1
COMPLETED
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Treatment Period 1
NOT COMPLETED
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Washout Period 1
STARTED
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Washout Period 1
COMPLETED
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Washout Period 1
NOT COMPLETED
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Treatment Period 2
STARTED
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Treatment Period 2
COMPLETED
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Treatment Period 2
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Washout Period 2
STARTED
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Washout Period 2
COMPLETED
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Washout Period 2
NOT COMPLETED
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Treatment Period 3
STARTED
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Treatment Period 3
COMPLETED
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Treatment Period 3
NOT COMPLETED
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Washout Period 3
STARTED
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Washout Period 3
COMPLETED
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Washout Period 3
NOT COMPLETED
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Treatment Period 4
STARTED
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Treatment Period 4
COMPLETED
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Treatment Period 4
NOT COMPLETED
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0
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Reasons for withdrawal
| Measure |
Seq 1: UMEC 250 µg, UMEC 500 µg, Tiotropium 18 µg, Placebo
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: umeclidinium bromide (UMEC) 250 micrograms (µg), UMEC 500 µg, Tiotropium 18 µg and placebo. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 2: UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg, Placebo
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg and placebo. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 3: UMEC 250 µg, Placebo, UMEC 500 µg, UMEC 1000 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, placebo, UMEC 500 µg and UMEC 1000 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 4: UMEC 250 µg, UMEC 500 µg, Placebo, UMEC 1000 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, UMEC 500 µg, placebo and UMEC 1000 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 5: Placebo, UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Placebo, UMEC 250 µg, UMEC 500 µg and UMEC 1000 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 6: UMEC 250 µg, Placebo, Tiotropium 18 µg, UMEC 500 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, placebo, Tiotropium 18 µg and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 7: Placebo, Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Placebo, Tiotropium 18 µg, UMEC 250 µg and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 8: Tiotropium 18 µg, Placebo, UMEC 250 µg, UMEC 500 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Tiotropium 18 µg, placebo, UMEC 250 µg and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 9: Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg, Placebo
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Tiotropium 18 µg, UMEC 250 µg, UMEC 500 µg and placebo. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 10: Tiotropium 18 µg, UMEC 250 µg, Placebo, UMEC 500 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Tiotropium 18 µg, UMEC 250 µg, placebo and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 11: Placebo, UMEC 250 µg, Tiotropium 18 µg, UMEC 500 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: Placebo, UMEC 250 µg, Tiotropium 18 µg and UMEC 500 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
Seq 12: UMEC 250 µg, Placebo, UMEC 500 µg, Tiotropium 18 µg
Participants received single doses of 4 treatments, over 4 treatment periods, in the following sequence: UMEC 250 µg, placebo, UMEC 500 µg and Tiotropium 18 µg. Treatment periods were seperated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
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Treatment Period 1
Adverse Event
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0
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0
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0
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0
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0
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0
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1
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0
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1
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0
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0
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1
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Treatment Period 2
Adverse Event
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0
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1
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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Baseline Characteristics
Safety Study Using GSK573719 And Tiotropium In Patients With Chronic Obstructive Pulmonary Disease
Baseline characteristics by cohort
| Measure |
All Study Treatments
n=24 Participants
Participants received a sequence containing 4 of the following 5 possible treatments: placebo, UMEC 250 µg, UMEC 500 µg, UMEC 1000 µg and Tiotropium 18 µg. Participants received each of the treatments in 1 of 4 single dose treatment periods, each of which was followed by a washout period. Treatment periods 1, 2, and 3 were followed by at least a 14-day washout period; Treatment period 4 was followed by a Follow-up visit within 10 days.
|
|---|---|
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Age, Continuous
|
56.0 Years
STANDARD_DEVIATION 5.32 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
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Race/Ethnicity, Customized
White - White/Caucasian/European
|
24 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From Day 1 of Treatment Period 1until Follow-up (up to 10 weeks)Population: All Subjects Population: all participants who received at least one dose of study medication.
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs and SAEs.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)
Any AE
|
6 Participants
|
9 Participants
|
8 Participants
|
4 Participants
|
3 Participants
|
|
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)
Any SAE
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. All participants with \>=1 post-Baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 1.
Resting heart rate was measured at pre-dose and 15 minutes (min), 45min, 1.5 hour (h) 4 h, 8 h, and 24 h post-dose of each treatment period and the maximum value for heart rate (0-4hours) was derived at rest. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Maximum (0-4 Hours) Heart Rate on Day 1 of Each Treatment Period
|
69.1 Beats per minute (bpm)
Standard Error 1.01
|
68.7 Beats per minute (bpm)
Standard Error 1.14
|
69.5 Beats per minute (bpm)
Standard Error 1.04
|
71.2 Beats per minute (bpm)
Standard Error 1.54
|
66.4 Beats per minute (bpm)
Standard Error 1.69
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. All participants with \>=1 post-Baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 1.
Resting heart rate was measured at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the weighted mean value for heart rate (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Weighted Mean (0-4 Hours) Heart Rate at Day 1 of Each Treatment Period
|
64.66 Beats per minute (bpm)
Standard Error 0.882
|
63.88 Beats per minute (bpm)
Standard Error 0.953
|
65.69 Beats per minute (bpm)
Standard Error 0.894
|
66.61 Beats per minute (bpm)
Standard Error 1.177
|
62.93 Beats per minute (bpm)
Standard Error 1.275
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. All participants with \>=1 post-Baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 1.
Resting systolic blood pressure was measured at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the maximum value for systolic blood pressure (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Maximum (0-4 Hours) Systolic Blood Pressure at Day 1 of Each Treatment Period
|
129.7 Millimeters of mercury (mmHg)
Standard Error 1.59
|
129.0 Millimeters of mercury (mmHg)
Standard Error 1.84
|
126.2 Millimeters of mercury (mmHg)
Standard Error 1.65
|
133.0 Millimeters of mercury (mmHg)
Standard Error 2.41
|
131.0 Millimeters of mercury (mmHg)
Standard Error 2.78
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. All participants with \>=1 post-Baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 1.
Resting systolic blood pressure was measured at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the weighted mean value for systolic blood pressure (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Weighted Mean (0-4 Hours) Systolic Blood Pressure at Day 1 of Each Treatment Period
|
124.49 Millimeters of mercury (mmHg)
Standard Error 1.445
|
122.07 Millimeters of mercury (mmHg)
Standard Error 1.670
|
122.61 Millimeters of mercury (mmHg)
Standard Error 1.503
|
125.61 Millimeters of mercury (mmHg)
Standard Error 2.190
|
124.80 Millimeters of mercury (mmHg)
Standard Error 2.517
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. All participants with \>=1 post-Baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 1.
Resting diastolic blood pressure was measured at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the maximum value for diastolic blood pressure (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Maximum (0-4 Hours) Diastolic Blood Pressure at Day 1 of Each Treatment Period
|
82.7 Millimeters of mercury (mmHg)
Standard Error 0.96
|
80.2 Millimeters of mercury (mmHg)
Standard Error 1.14
|
80.6 Millimeters of mercury (mmHg)
Standard Error 1.01
|
86.0 Millimeters of mercury (mmHg)
Standard Error 1.46
|
80.3 Millimeters of mercury (mmHg)
Standard Error 1.63
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. All participants with \>=1 post-Baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 1.
Resting diastolic blood pressure was measured at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the weighted mean value for diastolic blood pressure (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Weighted Mean (0-4 Hours) Diastolic Blood Pressure at Day 1 of Each Treatment Period
|
79.21 Millimeters of mercury (mmHg)
Standard Error 0.759
|
76.23 Millimeters of mercury (mmHg)
Standard Error 0.902
|
77.69 Millimeters of mercury (mmHg)
Standard Error 0.798
|
81.42 Millimeters of mercury (mmHg)
Standard Error 1.156
|
75.89 Millimeters of mercury (mmHg)
Standard Error 1.293
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. All participants with \>=1 post-Baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 1.
Twelve-lead ECGs (electrocardiograms) were performed to measure QT interval corrected according to Bazzet's formula (QTcB) at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the maximum value for QTcB (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Maximum (0-4 Hours) QTcB at Day 1 of Each Treatment Period
|
402.79 Milliseconds (msec)
Standard Error 2.263
|
399.48 Milliseconds (msec)
Standard Error 2.621
|
404.48 Milliseconds (msec)
Standard Error 2.396
|
401.25 Milliseconds (msec)
Standard Error 3.579
|
397.62 Milliseconds (msec)
Standard Error 3.867
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. All participants with \>=1 post-Baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 1.
Twelve-lead ECGs were performed to measure QTcB at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the weighted mean value for QTcB (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Weighted Mean (0-4 Hours) QTcB at Day 1 of Each Treatment Period
|
391.266 Milliseconds (msec)
Standard Error 1.7582
|
390.968 Milliseconds (msec)
Standard Error 2.0079
|
392.332 Milliseconds (msec)
Standard Error 1.8401
|
389.204 Milliseconds (msec)
Standard Error 2.7044
|
391.628 Milliseconds (msec)
Standard Error 2.9378
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. All participants with \>=1 post-Baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 1.
Twelve-lead ECGs were performed to measure QT interval corrected according to Fredericia's formula (QTcF) at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the maximum value for QTcF (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Maximum (0-4 Hours) QTcF at Day 1 of Each Treatment Period
|
394.25 Milliseconds (msec)
Standard Error 1.699
|
394.34 Milliseconds (msec)
Standard Error 1.977
|
395.60 Milliseconds (msec)
Standard Error 1.802
|
393.10 Milliseconds (msec)
Standard Error 2.604
|
393.93 Milliseconds (msec)
Standard Error 2.873
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. All participants with \>=1 post-Baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 1.
Twelve-lead ECGs were performed to measure QTcF at pre-dose and 15 minutes (min), 45 min, 1.5 hours (h), 4 h, 8 h and 24 h post-dose of each treatment period and the weighted mean value for QTcF (0-4 hours) was derived. Baseline is the mean of the 3 pre-dose measurements for each period. Participant level Baseline is the mean of the Baselines for each participant and period level Baseline is the difference between the Baseline and the participant level Baseline in each treatment period for each participant. Analysis was performed using a mixed model with participant level Baseline, period level Baseline, period and treatment group were fitted as fixed effects and participant as a random effect.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Weighted Mean (0-4 Hours) QTcF at Day 1 of Each Treatment Period
|
386.501 Milliseconds (msec)
Standard Error 1.3698
|
387.965 Milliseconds (msec)
Standard Error 1.5869
|
386.750 Milliseconds (msec)
Standard Error 1.4414
|
383.856 Milliseconds (msec)
Standard Error 2.1160
|
389.086 Milliseconds (msec)
Standard Error 2.3515
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. All participants with \>=1 post-Baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 1.
Twenty-four hour Holter monitoring was conducted to measure heart rate for the 24-hour period following dosing at each treatment period and the maximum value for heart rate (0-24 hours) was derived. Analysis was performed using a mixed model of period and treatment group fitted as fixed effects and participant as a random effect.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Maximum (0-24 Hours) Heart Rate as Measured From Holter Monitoring at Day 1 of Each Treatment Period
|
116.7 Beats per minute (bpm)
Standard Error 2.92
|
111.5 Beats per minute (bpm)
Standard Error 3.06
|
112.1 Beats per minute (bpm)
Standard Error 2.96
|
109.0 Beats per minute (bpm)
Standard Error 3.53
|
111.4 Beats per minute (bpm)
Standard Error 3.79
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. All participants with \>=1 post-Baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 1.
Twenty-four-hour Holter monitoring was conducted to measure heart rate for the 24-h period following dosing of each treatment period and the mean value for heart rate (0-24 hours) was derived. Analysis was performed using a mixed model of period and treatment group fitted as fixed effects and participant as a random effect.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Mean (0-24 Hours) Heart Rate as Measured From Holter Monitoring at Day 1 of Each Treatment Period
|
77.1 Beats per minute (bpm)
Standard Error 1.61
|
75.3 Beats per minute (bpm)
Standard Error 1.66
|
76.8 Beats per minute (bpm)
Standard Error 1.62
|
75.5 Beats per minute (bpm)
Standard Error 1.80
|
76.1 Beats per minute (bpm)
Standard Error 1.89
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population
Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, and total neutrophils at pre-dose and 24 hour (h) post-dose of each treatment period.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils Values at the Indicated Time Points on Day 1 of Each Treatment Period
Basophils, Pre-dose
|
0.65 Percentage
Standard Deviation 0.284
|
0.73 Percentage
Standard Deviation 0.366
|
0.74 Percentage
Standard Deviation 0.396
|
0.87 Percentage
Standard Deviation 0.275
|
0.71 Percentage
Standard Deviation 0.314
|
|
Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils Values at the Indicated Time Points on Day 1 of Each Treatment Period
Basophils, 24 h Post-dose
|
0.70 Percentage
Standard Deviation 0.434
|
0.65 Percentage
Standard Deviation 0.313
|
0.56 Percentage
Standard Deviation 0.292
|
0.58 Percentage
Standard Deviation 0.344
|
0.76 Percentage
Standard Deviation 0.558
|
|
Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils Values at the Indicated Time Points on Day 1 of Each Treatment Period
Eosinophils, Pre-dose
|
3.30 Percentage
Standard Deviation 2.336
|
3.46 Percentage
Standard Deviation 2.249
|
3.67 Percentage
Standard Deviation 2.813
|
4.03 Percentage
Standard Deviation 2.679
|
3.05 Percentage
Standard Deviation 1.562
|
|
Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils Values at the Indicated Time Points on Day 1 of Each Treatment Period
Eosinophils, 24 h Post-dose
|
3.34 Percentage
Standard Deviation 1.914
|
3.25 Percentage
Standard Deviation 1.839
|
3.30 Percentage
Standard Deviation 2.164
|
3.49 Percentage
Standard Deviation 2.437
|
3.38 Percentage
Standard Deviation 1.552
|
|
Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils Values at the Indicated Time Points on Day 1 of Each Treatment Period
Lymphocytes, Pre-dose
|
29.23 Percentage
Standard Deviation 6.820
|
30.66 Percentage
Standard Deviation 7.355
|
28.91 Percentage
Standard Deviation 9.279
|
33.70 Percentage
Standard Deviation 7.161
|
27.99 Percentage
Standard Deviation 7.637
|
|
Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils Values at the Indicated Time Points on Day 1 of Each Treatment Period
Lymphocytes, 24 h Post-dose
|
31.60 Percentage
Standard Deviation 6.387
|
30.86 Percentage
Standard Deviation 6.749
|
30.99 Percentage
Standard Deviation 6.558
|
31.72 Percentage
Standard Deviation 4.920
|
30.86 Percentage
Standard Deviation 6.298
|
|
Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils Values at the Indicated Time Points on Day 1 of Each Treatment Period
Monocytes, Pre-dose
|
8.53 Percentage
Standard Deviation 1.842
|
8.50 Percentage
Standard Deviation 2.467
|
8.60 Percentage
Standard Deviation 2.179
|
8.10 Percentage
Standard Deviation 1.626
|
9.33 Percentage
Standard Deviation 2.582
|
|
Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils Values at the Indicated Time Points on Day 1 of Each Treatment Period
Monocytes, 24 h Post-dose
|
8.10 Percentage
Standard Deviation 1.975
|
7.62 Percentage
Standard Deviation 1.934
|
8.23 Percentage
Standard Deviation 1.985
|
7.45 Percentage
Standard Deviation 1.406
|
9.40 Percentage
Standard Deviation 2.084
|
|
Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils Values at the Indicated Time Points on Day 1 of Each Treatment Period
Total neutrophils, Pre-dose
|
58.30 Percentage
Standard Deviation 8.159
|
56.64 Percentage
Standard Deviation 9.081
|
58.10 Percentage
Standard Deviation 10.941
|
53.32 Percentage
Standard Deviation 7.825
|
58.88 Percentage
Standard Deviation 9.403
|
|
Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils Values at the Indicated Time Points on Day 1 of Each Treatment Period
Total neutrophils, 24 h Post-dose
|
56.26 Percentage
Standard Deviation 7.166
|
57.62 Percentage
Standard Deviation 7.740
|
56.94 Percentage
Standard Deviation 7.164
|
56.78 Percentage
Standard Deviation 6.204
|
55.63 Percentage
Standard Deviation 7.699
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population
Blood samples were collected for the measurement of hemoglobin, MCHC, albumin and total protein at pre-dose and 24 hour (h) post-dose of each treatment period.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points on Day 1 of Each Treatment Period
Albumin, Pre-dose
|
39.16 Grams per liter (G/L)
Standard Deviation 2.020
|
39.24 Grams per liter (G/L)
Standard Deviation 2.109
|
39.33 Grams per liter (G/L)
Standard Deviation 1.955
|
39.10 Grams per liter (G/L)
Standard Deviation 1.545
|
39.49 Grams per liter (G/L)
Standard Deviation 2.775
|
|
Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points on Day 1 of Each Treatment Period
Albumin, 24 h Post-dose
|
39.36 Grams per liter (G/L)
Standard Deviation 1.682
|
38.75 Grams per liter (G/L)
Standard Deviation 1.742
|
38.76 Grams per liter (G/L)
Standard Deviation 1.744
|
39.30 Grams per liter (G/L)
Standard Deviation 1.750
|
38.38 Grams per liter (G/L)
Standard Deviation 2.930
|
|
Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points on Day 1 of Each Treatment Period
Total protein, Pre-dose
|
66.05 Grams per liter (G/L)
Standard Deviation 4.120
|
66.04 Grams per liter (G/L)
Standard Deviation 4.245
|
66.19 Grams per liter (G/L)
Standard Deviation 3.987
|
66.15 Grams per liter (G/L)
Standard Deviation 3.576
|
65.35 Grams per liter (G/L)
Standard Deviation 2.931
|
|
Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points on Day 1 of Each Treatment Period
Total protein, 24 h Post-dose
|
66.37 Grams per liter (G/L)
Standard Deviation 3.584
|
65.40 Grams per liter (G/L)
Standard Deviation 3.933
|
65.62 Grams per liter (G/L)
Standard Deviation 2.945
|
66.44 Grams per liter (G/L)
Standard Deviation 3.448
|
64.14 Grams per liter (G/L)
Standard Deviation 3.349
|
|
Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points on Day 1 of Each Treatment Period
Hemoglobin, Pre-dose
|
146.1 Grams per liter (G/L)
Standard Deviation 11.80
|
146.6 Grams per liter (G/L)
Standard Deviation 10.31
|
145.4 Grams per liter (G/L)
Standard Deviation 11.27
|
143.8 Grams per liter (G/L)
Standard Deviation 12.34
|
152.0 Grams per liter (G/L)
Standard Deviation 7.23
|
|
Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points on Day 1 of Each Treatment Period
Hemoglobin, 24 h Post-dose
|
147.0 Grams per liter (G/L)
Standard Deviation 12.53
|
145.5 Grams per liter (G/L)
Standard Deviation 11.01
|
144.1 Grams per liter (G/L)
Standard Deviation 10.97
|
143.5 Grams per liter (G/L)
Standard Deviation 14.77
|
148.9 Grams per liter (G/L)
Standard Deviation 5.59
|
|
Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points on Day 1 of Each Treatment Period
MCHC, Pre-dose
|
347.2 Grams per liter (G/L)
Standard Deviation 7.03
|
343.3 Grams per liter (G/L)
Standard Deviation 5.78
|
344.1 Grams per liter (G/L)
Standard Deviation 7.87
|
346.8 Grams per liter (G/L)
Standard Deviation 4.62
|
343.0 Grams per liter (G/L)
Standard Deviation 5.04
|
|
Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points on Day 1 of Each Treatment Period
MCHC, 24 h Post-dose
|
344.9 Grams per liter (G/L)
Standard Deviation 6.35
|
344.0 Grams per liter (G/L)
Standard Deviation 7.02
|
344.9 Grams per liter (G/L)
Standard Deviation 8.50
|
345.2 Grams per liter (G/L)
Standard Deviation 6.57
|
342.9 Grams per liter (G/L)
Standard Deviation 3.91
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population
Blood samples were collected for the measurement of hematocrit at pre-dose and 24 hour (h) post-dose of each treatment period.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Hematocrit Values at the Indicated Time Points on Day 1 of Each Treatment Period
Pre-dose
|
0.421 Proportion of red blood cells in blood
Standard Deviation 0.0335
|
0.428 Proportion of red blood cells in blood
Standard Deviation 0.0321
|
0.423 Proportion of red blood cells in blood
Standard Deviation 0.0326
|
0.416 Proportion of red blood cells in blood
Standard Deviation 0.0345
|
0.445 Proportion of red blood cells in blood
Standard Deviation 0.0193
|
|
Hematocrit Values at the Indicated Time Points on Day 1 of Each Treatment Period
24 h Post-dose
|
0.427 Proportion of red blood cells in blood
Standard Deviation 0.0352
|
0.424 Proportion of red blood cells in blood
Standard Deviation 0.0361
|
0.418 Proportion of red blood cells in blood
Standard Deviation 0.0322
|
0.417 Proportion of red blood cells in blood
Standard Deviation 0.0419
|
0.434 Proportion of red blood cells in blood
Standard Deviation 0.0192
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population
Blood samples were collected for the measurement of the mean corpuscle hemoglobin at pre-dose and 24 hour (h) post-dose of each treatment period.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Mean Corpuscle Hemoglobin Values at the Indicated Time Points on Day 1 of Each Treatment Period
Pre-dose
|
32.56 picograms/cell (pg)
Standard Deviation 1.402
|
32.36 picograms/cell (pg)
Standard Deviation 1.365
|
32.36 picograms/cell (pg)
Standard Deviation 1.513
|
32.29 picograms/cell (pg)
Standard Deviation 1.393
|
32.86 picograms/cell (pg)
Standard Deviation 0.971
|
|
Mean Corpuscle Hemoglobin Values at the Indicated Time Points on Day 1 of Each Treatment Period
24 Hour Post-dose
|
32.41 picograms/cell (pg)
Standard Deviation 1.354
|
32.36 picograms/cell (pg)
Standard Deviation 1.208
|
32.36 picograms/cell (pg)
Standard Deviation 1.359
|
32.15 picograms/cell (pg)
Standard Deviation 1.309
|
32.79 picograms/cell (pg)
Standard Deviation 1.018
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population
Blood samples were collected for the measurement of the mean corpuscle volume at pre-dose and 24 hour (h) post-dose of each treatment period.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Mean Corpuscle Volume Values at the Indicated Time Points on Day 1 of Each Treatment Period
Pre-dose
|
93.78 Femtoliters (FL)
Standard Deviation 3.701
|
94.23 Femtoliters (FL)
Standard Deviation 3.547
|
94.04 Femtoliters (FL)
Standard Deviation 3.734
|
93.11 Femtoliters (FL)
Standard Deviation 3.840
|
95.83 Femtoliters (FL)
Standard Deviation 3.310
|
|
Mean Corpuscle Volume Values at the Indicated Time Points on Day 1 of Each Treatment Period
24 h Post-dose
|
93.99 Femtoliters (FL)
Standard Deviation 3.597
|
94.09 Femtoliters (FL)
Standard Deviation 3.763
|
93.85 Femtoliters (FL)
Standard Deviation 3.955
|
93.15 Femtoliters (FL)
Standard Deviation 3.652
|
95.65 Femtoliters (FL)
Standard Deviation 2.946
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population
Blood samples were collected for the measurement of the red blood cells count at pre-dose and 24 hour (h) post-dose of each treatment period.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Red Blood Cells Count Values at the Indicated Time Points on Day 1 of Each Treatment Period
Pre-dose
|
4.493 10^12 cells per liter (TI/L)
Standard Deviation 0.3992
|
4.537 10^12 cells per liter (TI/L)
Standard Deviation 0.3487
|
4.498 10^12 cells per liter (TI/L)
Standard Deviation 0.3758
|
4.456 10^12 cells per liter (TI/L)
Standard Deviation 0.3987
|
4.625 10^12 cells per liter (TI/L)
Standard Deviation 0.2469
|
|
Red Blood Cells Count Values at the Indicated Time Points on Day 1 of Each Treatment Period
24 h Post-dose
|
4.539 10^12 cells per liter (TI/L)
Standard Deviation 0.3960
|
4.498 10^12 cells per liter (TI/L)
Standard Deviation 0.3760
|
4.457 10^12 cells per liter (TI/L)
Standard Deviation 0.3614
|
4.464 10^12 cells per liter (TI/L)
Standard Deviation 0.4511
|
4.543 10^12 cells per liter (TI/L)
Standard Deviation 0.2232
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population
Blood samples were collected for the measurement of platelets count and WBC count at pre-dose and 24 hour (h) post-dose of each treatment period.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Platelets Count and White Blood Cells (WBC) Count Values at the Indicated Time Points on Day 1 of Each Treatment Period
Platelets count, Pre-dose
|
247.2 10^9 cells per liter (GI/L)
Standard Deviation 70.84
|
245.0 10^9 cells per liter (GI/L)
Standard Deviation 71.33
|
250.7 10^9 cells per liter (GI/L)
Standard Deviation 69.06
|
235.9 10^9 cells per liter (GI/L)
Standard Deviation 47.15
|
243.4 10^9 cells per liter (GI/L)
Standard Deviation 104.43
|
|
Platelets Count and White Blood Cells (WBC) Count Values at the Indicated Time Points on Day 1 of Each Treatment Period
Platelets count, 24 h Post-dose
|
248.8 10^9 cells per liter (GI/L)
Standard Deviation 69.53
|
245.4 10^9 cells per liter (GI/L)
Standard Deviation 76.18
|
250.3 10^9 cells per liter (GI/L)
Standard Deviation 63.51
|
237.9 10^9 cells per liter (GI/L)
Standard Deviation 46.30
|
237.6 10^9 cells per liter (GI/L)
Standard Deviation 101.59
|
|
Platelets Count and White Blood Cells (WBC) Count Values at the Indicated Time Points on Day 1 of Each Treatment Period
WBC count, Pre-dose
|
7.623 10^9 cells per liter (GI/L)
Standard Deviation 1.7271
|
7.130 10^9 cells per liter (GI/L)
Standard Deviation 1.6116
|
7.560 10^9 cells per liter (GI/L)
Standard Deviation 1.6860
|
7.121 10^9 cells per liter (GI/L)
Standard Deviation 1.2807
|
6.763 10^9 cells per liter (GI/L)
Standard Deviation 1.0249
|
|
Platelets Count and White Blood Cells (WBC) Count Values at the Indicated Time Points on Day 1 of Each Treatment Period
WBC count, 24 h Post-dose
|
7.520 10^9 cells per liter (GI/L)
Standard Deviation 1.3103
|
7.385 10^9 cells per liter (GI/L)
Standard Deviation 1.7548
|
7.218 10^9 cells per liter (GI/L)
Standard Deviation 1.4426
|
7.999 10^9 cells per liter (GI/L)
Standard Deviation 1.6531
|
6.623 10^9 cells per liter (GI/L)
Standard Deviation 1.2366
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been summarized for different parameters/at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
Blood samples were collected for the measurement of ALP, ALT, AST, CPK, and GGT at pre-dose and 24 hour (h) post-dose of each treatment period.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points on Day 1 of Each Treatment Period
ALP, Pre-dose, n=21, 22, 21, 13, 8
|
67.04 International units per liter (IU/L)
Standard Deviation 17.260
|
65.32 International units per liter (IU/L)
Standard Deviation 12.687
|
66.60 International units per liter (IU/L)
Standard Deviation 13.127
|
63.37 International units per liter (IU/L)
Standard Deviation 13.469
|
71.06 International units per liter (IU/L)
Standard Deviation 19.304
|
|
Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points on Day 1 of Each Treatment Period
ALP, 24 h Post-dose, n=21, 22, 21, 13, 8
|
67.20 International units per liter (IU/L)
Standard Deviation 18.388
|
65.04 International units per liter (IU/L)
Standard Deviation 15.289
|
64.96 International units per liter (IU/L)
Standard Deviation 14.933
|
61.76 International units per liter (IU/L)
Standard Deviation 12.253
|
71.84 International units per liter (IU/L)
Standard Deviation 21.099
|
|
Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points on Day 1 of Each Treatment Period
ALT, Pre-dose,n=21, 22, 21, 13, 8
|
23.6 International units per liter (IU/L)
Standard Deviation 11.67
|
24.1 International units per liter (IU/L)
Standard Deviation 9.80
|
21.3 International units per liter (IU/L)
Standard Deviation 8.37
|
26.2 International units per liter (IU/L)
Standard Deviation 10.53
|
19.1 International units per liter (IU/L)
Standard Deviation 5.36
|
|
Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points on Day 1 of Each Treatment Period
ALT, 24 h Post-dose,n=21, 22, 21, 13, 8
|
23.3 International units per liter (IU/L)
Standard Deviation 12.29
|
23.0 International units per liter (IU/L)
Standard Deviation 9.36
|
20.5 International units per liter (IU/L)
Standard Deviation 7.56
|
25.6 International units per liter (IU/L)
Standard Deviation 9.69
|
17.8 International units per liter (IU/L)
Standard Deviation 5.39
|
|
Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points on Day 1 of Each Treatment Period
AST, Pre-dose, n=21, 22, 20, 13, 8
|
21.98 International units per liter (IU/L)
Standard Deviation 7.525
|
24.55 International units per liter (IU/L)
Standard Deviation 6.689
|
22.13 International units per liter (IU/L)
Standard Deviation 5.358
|
23.03 International units per liter (IU/L)
Standard Deviation 6.923
|
22.09 International units per liter (IU/L)
Standard Deviation 4.995
|
|
Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points on Day 1 of Each Treatment Period
AST, 24 h Post-dose, n=21, 22, 21, 13, 8
|
21.68 International units per liter (IU/L)
Standard Deviation 8.625
|
22.01 International units per liter (IU/L)
Standard Deviation 7.048
|
20.58 International units per liter (IU/L)
Standard Deviation 5.761
|
20.75 International units per liter (IU/L)
Standard Deviation 6.947
|
19.23 International units per liter (IU/L)
Standard Deviation 5.473
|
|
Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points on Day 1 of Each Treatment Period
CPK, Pre-dose, n=21, 22, 21, 13, 8
|
124.33 International units per liter (IU/L)
Standard Deviation 89.568
|
101.88 International units per liter (IU/L)
Standard Deviation 49.410
|
104.39 International units per liter (IU/L)
Standard Deviation 42.381
|
100.16 International units per liter (IU/L)
Standard Deviation 44.497
|
117.08 International units per liter (IU/L)
Standard Deviation 61.189
|
|
Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points on Day 1 of Each Treatment Period
CPK, 24 h Post-dose, n=21, 22, 21, 13, 8
|
99.97 International units per liter (IU/L)
Standard Deviation 61.307
|
82.81 International units per liter (IU/L)
Standard Deviation 30.913
|
83.77 International units per liter (IU/L)
Standard Deviation 29.233
|
87.78 International units per liter (IU/L)
Standard Deviation 37.566
|
109.36 International units per liter (IU/L)
Standard Deviation 90.411
|
|
Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points on Day 1 of Each Treatment Period
GGT, Pre-dose, n=21, 22, 21, 13, 8
|
27.81 International units per liter (IU/L)
Standard Deviation 18.287
|
26.41 International units per liter (IU/L)
Standard Deviation 14.704
|
26.41 International units per liter (IU/L)
Standard Deviation 17.573
|
29.86 International units per liter (IU/L)
Standard Deviation 21.391
|
19.94 International units per liter (IU/L)
Standard Deviation 6.369
|
|
Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points on Day 1 of Each Treatment Period
GGT, 24 h Post-dose, n=21, 22, 21, 13, 8
|
27.14 International units per liter (IU/L)
Standard Deviation 16.806
|
25.33 International units per liter (IU/L)
Standard Deviation 13.962
|
25.89 International units per liter (IU/L)
Standard Deviation 18.218
|
29.38 International units per liter (IU/L)
Standard Deviation 19.277
|
19.59 International units per liter (IU/L)
Standard Deviation 6.431
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population
Blood samples were collected for the measurement of total bilirubin, creatinine, and uric acid at pre-dose and 24 hour (h) post-dose of each treatment period.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points on Day 1 of Each Treatment Period
Total bilirubin, 24 h Post-dose
|
8.70 Micromoles per liter (µmol/L)
Standard Deviation 2.602
|
8.26 Micromoles per liter (µmol/L)
Standard Deviation 2.955
|
9.48 Micromoles per liter (µmol/L)
Standard Deviation 3.523
|
10.27 Micromoles per liter (µmol/L)
Standard Deviation 3.086
|
6.83 Micromoles per liter (µmol/L)
Standard Deviation 2.036
|
|
Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points on Day 1 of Each Treatment Period
Creatinine, Pre-dose
|
78.55 Micromoles per liter (µmol/L)
Standard Deviation 7.589
|
80.50 Micromoles per liter (µmol/L)
Standard Deviation 8.012
|
80.24 Micromoles per liter (µmol/L)
Standard Deviation 10.079
|
78.64 Micromoles per liter (µmol/L)
Standard Deviation 8.296
|
79.79 Micromoles per liter (µmol/L)
Standard Deviation 8.333
|
|
Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points on Day 1 of Each Treatment Period
Creatinine, 24 h Post-dose
|
78.02 Micromoles per liter (µmol/L)
Standard Deviation 6.451
|
79.08 Micromoles per liter (µmol/L)
Standard Deviation 8.324
|
78.14 Micromoles per liter (µmol/L)
Standard Deviation 9.684
|
76.44 Micromoles per liter (µmol/L)
Standard Deviation 7.241
|
76.29 Micromoles per liter (µmol/L)
Standard Deviation 8.999
|
|
Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points on Day 1 of Each Treatment Period
Uric acid, Pre-dose
|
295.86 Micromoles per liter (µmol/L)
Standard Deviation 64.155
|
301.24 Micromoles per liter (µmol/L)
Standard Deviation 77.192
|
303.18 Micromoles per liter (µmol/L)
Standard Deviation 77.389
|
317.09 Micromoles per liter (µmol/L)
Standard Deviation 76.125
|
281.19 Micromoles per liter (µmol/L)
Standard Deviation 67.657
|
|
Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points on Day 1 of Each Treatment Period
Uric acid, 24 h Post-dose
|
285.55 Micromoles per liter (µmol/L)
Standard Deviation 63.350
|
293.21 Micromoles per liter (µmol/L)
Standard Deviation 65.637
|
296.28 Micromoles per liter (µmol/L)
Standard Deviation 70.307
|
306.26 Micromoles per liter (µmol/L)
Standard Deviation 72.701
|
268.64 Micromoles per liter (µmol/L)
Standard Deviation 61.525
|
|
Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points on Day 1 of Each Treatment Period
Total bilirubin, Pre-dose
|
7.92 Micromoles per liter (µmol/L)
Standard Deviation 2.457
|
8.33 Micromoles per liter (µmol/L)
Standard Deviation 2.234
|
8.66 Micromoles per liter (µmol/L)
Standard Deviation 3.387
|
8.68 Micromoles per liter (µmol/L)
Standard Deviation 2.238
|
7.69 Micromoles per liter (µmol/L)
Standard Deviation 1.549
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed for different parameters/at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
Blood samples were collected for the measurement of the calcium, bicarbonate, chloride, glucose, IP, potassium, sodium, and urea at pre-dose and 24 hour (h) post-dose of each treatment period.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
Calcium, Pre-dose, n=21, 22, 21, 13, 8
|
2.283 Millimoles per liter (mmol/L)
Standard Deviation 0.0729
|
2.277 Millimoles per liter (mmol/L)
Standard Deviation 0.0861
|
2.267 Millimoles per liter (mmol/L)
Standard Deviation 0.0809
|
2.242 Millimoles per liter (mmol/L)
Standard Deviation 0.0625
|
2.278 Millimoles per liter (mmol/L)
Standard Deviation 0.0547
|
|
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
Bicarbonate, 24 h Post-dose, n=21, 22, 21, 13, 7
|
22.98 Millimoles per liter (mmol/L)
Standard Deviation 2.414
|
22.62 Millimoles per liter (mmol/L)
Standard Deviation 2.995
|
23.30 Millimoles per liter (mmol/L)
Standard Deviation 2.600
|
23.80 Millimoles per liter (mmol/L)
Standard Deviation 2.822
|
25.14 Millimoles per liter (mmol/L)
Standard Deviation 2.738
|
|
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
Potassium, Pre-dose, n=21, 22, 21, 13, 8
|
4.283 Millimoles per liter (mmol/L)
Standard Deviation 0.3178
|
4.177 Millimoles per liter (mmol/L)
Standard Deviation 0.2537
|
4.209 Millimoles per liter (mmol/L)
Standard Deviation 0.2255
|
4.248 Millimoles per liter (mmol/L)
Standard Deviation 0.2717
|
4.193 Millimoles per liter (mmol/L)
Standard Deviation 0.1896
|
|
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
Potassium, 24 h Post-dose, n=21, 22, 21, 13, 8
|
4.270 Millimoles per liter (mmol/L)
Standard Deviation 0.2340
|
4.274 Millimoles per liter (mmol/L)
Standard Deviation 0.3311
|
4.266 Millimoles per liter (mmol/L)
Standard Deviation 0.3065
|
4.279 Millimoles per liter (mmol/L)
Standard Deviation 0.3587
|
4.359 Millimoles per liter (mmol/L)
Standard Deviation 0.3642
|
|
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
Sodium, Pre-dose,n=21, 22, 21, 13, 8
|
140.45 Millimoles per liter (mmol/L)
Standard Deviation 2.253
|
140.95 Millimoles per liter (mmol/L)
Standard Deviation 1.932
|
140.84 Millimoles per liter (mmol/L)
Standard Deviation 1.551
|
141.07 Millimoles per liter (mmol/L)
Standard Deviation 0.825
|
140.86 Millimoles per liter (mmol/L)
Standard Deviation 2.458
|
|
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
Calcium, 24 h Post-dose, n=21, 22, 21, 13, 8
|
2.270 Millimoles per liter (mmol/L)
Standard Deviation 0.0891
|
2.290 Millimoles per liter (mmol/L)
Standard Deviation 0.0713
|
2.265 Millimoles per liter (mmol/L)
Standard Deviation 0.0704
|
2.244 Millimoles per liter (mmol/L)
Standard Deviation 0.0864
|
2.280 Millimoles per liter (mmol/L)
Standard Deviation 0.0428
|
|
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
Chloride, Pre-dose, n=21, 22, 21, 13, 8
|
106.88 Millimoles per liter (mmol/L)
Standard Deviation 2.727
|
107.11 Millimoles per liter (mmol/L)
Standard Deviation 1.972
|
106.42 Millimoles per liter (mmol/L)
Standard Deviation 1.857
|
107.26 Millimoles per liter (mmol/L)
Standard Deviation 2.738
|
106.49 Millimoles per liter (mmol/L)
Standard Deviation 2.255
|
|
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
Chloride, 24 h Post-dose, n=21, 22, 21, 13, 8
|
107.18 Millimoles per liter (mmol/L)
Standard Deviation 1.875
|
107.10 Millimoles per liter (mmol/L)
Standard Deviation 2.457
|
106.94 Millimoles per liter (mmol/L)
Standard Deviation 2.002
|
107.17 Millimoles per liter (mmol/L)
Standard Deviation 2.830
|
106.59 Millimoles per liter (mmol/L)
Standard Deviation 1.460
|
|
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
Glucose, Pre-dose, n=21, 22, 21, 13, 8
|
5.225 Millimoles per liter (mmol/L)
Standard Deviation 0.5294
|
5.046 Millimoles per liter (mmol/L)
Standard Deviation 0.5583
|
5.082 Millimoles per liter (mmol/L)
Standard Deviation 0.5882
|
5.098 Millimoles per liter (mmol/L)
Standard Deviation 0.4362
|
5.326 Millimoles per liter (mmol/L)
Standard Deviation 0.6739
|
|
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
Glucose, 24 h Post-dose, n=21, 22, 21, 13, 8
|
5.278 Millimoles per liter (mmol/L)
Standard Deviation 0.5800
|
5.203 Millimoles per liter (mmol/L)
Standard Deviation 0.6391
|
5.224 Millimoles per liter (mmol/L)
Standard Deviation 0.5500
|
5.031 Millimoles per liter (mmol/L)
Standard Deviation 0.3691
|
5.291 Millimoles per liter (mmol/L)
Standard Deviation 0.5350
|
|
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
Bicarbonate, Pre-dose, n=21, 22, 21, 13, 8
|
22.41 Millimoles per liter (mmol/L)
Standard Deviation 2.609
|
22.95 Millimoles per liter (mmol/L)
Standard Deviation 2.295
|
23.28 Millimoles per liter (mmol/L)
Standard Deviation 2.698
|
23.08 Millimoles per liter (mmol/L)
Standard Deviation 2.401
|
22.98 Millimoles per liter (mmol/L)
Standard Deviation 4.179
|
|
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
Sodium, 24 h Post-dose, n=21, 22, 21, 13, 8
|
140.90 Millimoles per liter (mmol/L)
Standard Deviation 1.674
|
140.68 Millimoles per liter (mmol/L)
Standard Deviation 1.864
|
140.93 Millimoles per liter (mmol/L)
Standard Deviation 1.610
|
141.13 Millimoles per liter (mmol/L)
Standard Deviation 1.165
|
140.56 Millimoles per liter (mmol/L)
Standard Deviation 1.749
|
|
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
IP, Pre-dose, n=21, 22, 21, 13, 8
|
1.153 Millimoles per liter (mmol/L)
Standard Deviation 0.1271
|
1.095 Millimoles per liter (mmol/L)
Standard Deviation 0.1026
|
1.135 Millimoles per liter (mmol/L)
Standard Deviation 0.1406
|
1.105 Millimoles per liter (mmol/L)
Standard Deviation 0.1490
|
1.161 Millimoles per liter (mmol/L)
Standard Deviation 0.1763
|
|
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
IP, 24 h Post-dose, n=21, 22, 21, 13, 8
|
1.131 Millimoles per liter (mmol/L)
Standard Deviation 0.1455
|
1.118 Millimoles per liter (mmol/L)
Standard Deviation 0.1391
|
1.143 Millimoles per liter (mmol/L)
Standard Deviation 0.1486
|
1.121 Millimoles per liter (mmol/L)
Standard Deviation 0.1735
|
1.158 Millimoles per liter (mmol/L)
Standard Deviation 0.1179
|
|
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
Urea, Pre-dose, n=21, 22, 21, 13, 8
|
4.905 Millimoles per liter (mmol/L)
Standard Deviation 1.2041
|
4.629 Millimoles per liter (mmol/L)
Standard Deviation 0.9289
|
5.002 Millimoles per liter (mmol/L)
Standard Deviation 1.1933
|
4.904 Millimoles per liter (mmol/L)
Standard Deviation 0.9358
|
4.820 Millimoles per liter (mmol/L)
Standard Deviation 1.2474
|
|
Calcium, Bicarbonate, Chloride, Glucose, Inorganic Phosphorus (IP), Potassium, Sodium, and Urea Values at the Indicated Time Points on Day 1 of Each Treatment Period
Urea, 24 h Post-dose, n=21, 22, 21, 13, 8
|
4.700 Millimoles per liter (mmol/L)
Standard Deviation 0.8093
|
4.721 Millimoles per liter (mmol/L)
Standard Deviation 0.9688
|
4.710 Millimoles per liter (mmol/L)
Standard Deviation 0.9958
|
4.579 Millimoles per liter (mmol/L)
Standard Deviation 0.8701
|
4.764 Millimoles per liter (mmol/L)
Standard Deviation 1.6021
|
PRIMARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been summarized for different parameters/at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. FEV1 and FVC measurements were taken at pre-dose and 1 hour (h), 2 h, 6 h, 9 h, 12 h and 24 h post-dose of each treatment period.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points on Day 1 of Each Treatment Period
FEV1, Pre-dose, n= 21, 22, 21, 13, 8
|
1.637 Liters
Standard Deviation 0.3991
|
1.559 Liters
Standard Deviation 0.2867
|
1.589 Liters
Standard Deviation 0.2871
|
1.732 Liters
Standard Deviation 0.2080
|
1.400 Liters
Standard Deviation 0.2545
|
|
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points on Day 1 of Each Treatment Period
FEV1, 1h, n=21, 20, 21, 13, 8
|
1.670 Liters
Standard Deviation 0.4130
|
1.874 Liters
Standard Deviation 0.3414
|
1.905 Liters
Standard Deviation 0.3574
|
1.966 Liters
Standard Deviation 0.3781
|
1.663 Liters
Standard Deviation 0.3250
|
|
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points on Day 1 of Each Treatment Period
FEV1, 2h, n= 21, 20, 21, 13, 8
|
1.689 Liters
Standard Deviation 0.4172
|
1.969 Liters
Standard Deviation 0.3760
|
2.015 Liters
Standard Deviation 0.3512
|
2.123 Liters
Standard Deviation 0.3757
|
1.696 Liters
Standard Deviation 0.3311
|
|
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points on Day 1 of Each Treatment Period
FEV1, 6h, n=21, 22, 21, 13, 8
|
1.700 Liters
Standard Deviation 0.4055
|
2.000 Liters
Standard Deviation 0.4251
|
2.073 Liters
Standard Deviation 0.3343
|
2.198 Liters
Standard Deviation 0.3329
|
1.841 Liters
Standard Deviation 0.4372
|
|
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points on Day 1 of Each Treatment Period
FEV1, 9h, n=21, 19, 21, 13, 7
|
1.754 Liters
Standard Deviation 0.3664
|
1.984 Liters
Standard Deviation 0.3554
|
2.010 Liters
Standard Deviation 0.3113
|
2.135 Liters
Standard Deviation 0.2850
|
1.767 Liters
Standard Deviation 0.4555
|
|
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points on Day 1 of Each Treatment Period
FEV1, 12h, n=21, 22, 21, 13,8
|
1.688 Liters
Standard Deviation 0.3797
|
1.933 Liters
Standard Deviation 0.3756
|
1.988 Liters
Standard Deviation 0.3463
|
2.103 Liters
Standard Deviation 0.3633
|
1.619 Liters
Standard Deviation 0.4182
|
|
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points on Day 1 of Each Treatment Period
FEV1, 24h, =21, 22, 21, 13, 8
|
1.612 Liters
Standard Deviation 0.3189
|
1.830 Liters
Standard Deviation 0.4033
|
1.817 Liters
Standard Deviation 0.3569
|
1.978 Liters
Standard Deviation 0.3416
|
1.454 Liters
Standard Deviation 0.3135
|
|
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points on Day 1 of Each Treatment Period
FVC, Pre-dose, n=21, 22, 21, 13, 8
|
3.438 Liters
Standard Deviation 0.8138
|
3.247 Liters
Standard Deviation 0.7574
|
3.337 Liters
Standard Deviation 0.7139
|
3.640 Liters
Standard Deviation 0.7869
|
3.080 Liters
Standard Deviation 0.6682
|
|
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points on Day 1 of Each Treatment Period
FVC, 1h, n=21, 20, 21, 13, 8
|
3.490 Liters
Standard Deviation 0.8721
|
3.751 Liters
Standard Deviation 0.8688
|
3.845 Liters
Standard Deviation 0.7974
|
4.006 Liters
Standard Deviation 0.9430
|
3.631 Liters
Standard Deviation 0.7223
|
|
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points on Day 1 of Each Treatment Period
FVC, 2h, n=21, 20, 21, 13, 8
|
3.545 Liters
Standard Deviation 0.8796
|
3.877 Liters
Standard Deviation 0.9571
|
3.976 Liters
Standard Deviation 0.8479
|
4.205 Liters
Standard Deviation 0.9935
|
3.674 Liters
Standard Deviation 0.7766
|
|
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points on Day 1 of Each Treatment Period
FVC, 6h, n=21, 22, 21, 13, 8
|
3.572 Liters
Standard Deviation 0.8555
|
3.940 Liters
Standard Deviation 0.9583
|
4.064 Liters
Standard Deviation 0.8822
|
4.257 Liters
Standard Deviation 1.0390
|
3.780 Liters
Standard Deviation 0.8023
|
|
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points on Day 1 of Each Treatment Period
FVC, 9h, n=21, 19, 21, 13, 7
|
3.662 Liters
Standard Deviation 0.8436
|
4.015 Liters
Standard Deviation 0.8461
|
3.969 Liters
Standard Deviation 0.8783
|
4.184 Liters
Standard Deviation 0.9694
|
3.544 Liters
Standard Deviation 0.7176
|
|
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points on Day 1 of Each Treatment Period
FVC, 12h, n=21, 22, 21, 13, 8
|
3.595 Liters
Standard Deviation 0.8178
|
3.841 Liters
Standard Deviation 0.9190
|
3.923 Liters
Standard Deviation 0.8966
|
4.130 Liters
Standard Deviation 1.0544
|
3.563 Liters
Standard Deviation 0.7816
|
|
Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points on Day 1 of Each Treatment Period
FVC, 24h, n=21, 22, 21, 13, 8
|
3.389 Liters
Standard Deviation 0.7272
|
3.712 Liters
Standard Deviation 0.9878
|
3.705 Liters
Standard Deviation 0.8597
|
3.993 Liters
Standard Deviation 0.9759
|
3.280 Liters
Standard Deviation 0.6741
|
SECONDARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: Pharmacokinetic (PK) Population:all participants in the All Subjects Population for whom a PK sample was obtained and analyzed.
Blood samples were collected to determine the plasma concentrations of UMEC from pre-dose up to 24 hour post-dose of each treatment period to derive the AUC(0-2) and AUC(0-t). Blood samples for PK analysis of UMEC were obtained on Day 1at pre-dose and 5 minutes (min), 15 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, and 24 h post UMEC dose administration.
Outcome measures
| Measure |
Placebo
n=22 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Area Under Concentration-time Curve From Time 0 to 2 Hours [AUC(0-2)] and Area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration [AUC(0-t)] of UMEC
AUC(0-2)
|
0.10264 hr * nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 58.9
|
0.27099 hr * nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 58.5
|
0.71522 hr * nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 21.8
|
—
|
—
|
|
Area Under Concentration-time Curve From Time 0 to 2 Hours [AUC(0-2)] and Area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration [AUC(0-t)] of UMEC
AUC(0-t)
|
0.10271 hr * nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 70.0
|
0.35491 hr * nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 65.2
|
0.96100 hr * nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 27.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: PK Population
Blood samples were collected to determine the plasma concentrations of UMEC from pre-dose up to 24 hour post-dose of each treatment period to derive the Cmax. Blood samples for PK analysis of UMEC were obtained on Day 1at pre-dose and 5 minutes (min), 15 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, and 24 h post UMEC dose administration.
Outcome measures
| Measure |
Placebo
n=22 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of UMEC
|
0.12615 ng/mL
Geometric Coefficient of Variation 43.4
|
0.30389 ng/mL
Geometric Coefficient of Variation 40.7
|
0.83228 ng/mL
Geometric Coefficient of Variation 22.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: PK Population. Only those participants with non-missing observations (including non-calculable values) were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed for different parameters/at different time points, so the overall number of participants analyzed reflects everyone in the PK Population
Blood samples were collected to determine the plasma concentrations of UMEC from pre-dose up to 24 hour post-dose of each treatment period to derive tmax, tlast and t1/2. Blood samples for PK analysis of UMEC were obtained on Day 1at pre-dose and 5 minutes (min), 15 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, and 24 h post UMEC dose administration.
Outcome measures
| Measure |
Placebo
n=22 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Time of Maximum Observed Plasma Concentration (Tmax), Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast), and Plasma Half-life (t1/2) of UMEC
tmax, n=22, 21, 13
|
0.090 Hours
Interval 0.08 to 0.5
|
0.100 Hours
Interval 0.07 to 0.27
|
0.250 Hours
Interval 0.08 to 0.28
|
—
|
—
|
|
Time of Maximum Observed Plasma Concentration (Tmax), Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast), and Plasma Half-life (t1/2) of UMEC
tlast, n=22, 21, 13
|
1.975 Hours
Interval 0.47 to 4.07
|
4.030 Hours
Interval 1.0 to 24.0
|
6.000 Hours
Interval 4.0 to 15.95
|
—
|
—
|
|
Time of Maximum Observed Plasma Concentration (Tmax), Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast), and Plasma Half-life (t1/2) of UMEC
t1/2, n=22, 21, 13
|
NA Hours
Due to the large amount of non-quantifiable (NQ) data in the distribution and elimination phase at 250mcg dose level, all t½ values could not be calculated and median and the confidence interval (CI) could not be estimated.
|
1.24490 Hours
Interval 0.7079 to 3.6743
|
1.19780 Hours
Interval 0.7889 to 20.2309
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: PK Population
Urine samples were collected to determine the urine concentrations of UMEC from 0 min up to 48 hours post-dose of each treatment period to derive Ae(0-2), Ae(0-8), Ae(0-12), Ae(0-24), Ae(0-48), AUER(0-18) and AUER(0-36). Urine samples for PK analysis of UMEC were obtained on Day 1; a single sample was collected at each of the following timepoints: 0-2 h, 2-8 h, 8-12 h, 12-24 h and 24-48 h post UMEC dose administration.
Outcome measures
| Measure |
Placebo
n=22 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Amount of Drug Excreted Unchanged in Urine From Time Zero to: 2h [Ae(0-2)] , 8h [Ae(0-8)], 12h [Ae(0-12)], 24h [Ae(0-24)], and 48h [Ae(0-48)]; and Area Under the Excretion Rate Curve From Time Zero to: 18h [AUER(0-18)] and 36h [AUER(0-36)] for UMEC
Ae(0-2)
|
734.525 ng
Geometric Coefficient of Variation 56.0
|
1793.951 ng
Geometric Coefficient of Variation 40.5
|
4456.582 ng
Geometric Coefficient of Variation 43.5
|
—
|
—
|
|
Amount of Drug Excreted Unchanged in Urine From Time Zero to: 2h [Ae(0-2)] , 8h [Ae(0-8)], 12h [Ae(0-12)], 24h [Ae(0-24)], and 48h [Ae(0-48)]; and Area Under the Excretion Rate Curve From Time Zero to: 18h [AUER(0-18)] and 36h [AUER(0-36)] for UMEC
Ae(0-8)
|
1676.101 ng
Geometric Coefficient of Variation 54.7
|
4146.206 ng
Geometric Coefficient of Variation 50.6
|
9935.792 ng
Geometric Coefficient of Variation 33.4
|
—
|
—
|
|
Amount of Drug Excreted Unchanged in Urine From Time Zero to: 2h [Ae(0-2)] , 8h [Ae(0-8)], 12h [Ae(0-12)], 24h [Ae(0-24)], and 48h [Ae(0-48)]; and Area Under the Excretion Rate Curve From Time Zero to: 18h [AUER(0-18)] and 36h [AUER(0-36)] for UMEC
Ae(0-12)
|
1987.910 ng
Geometric Coefficient of Variation 50.0
|
4712.376 ng
Geometric Coefficient of Variation 50.1
|
10983.771 ng
Geometric Coefficient of Variation 34.5
|
—
|
—
|
|
Amount of Drug Excreted Unchanged in Urine From Time Zero to: 2h [Ae(0-2)] , 8h [Ae(0-8)], 12h [Ae(0-12)], 24h [Ae(0-24)], and 48h [Ae(0-48)]; and Area Under the Excretion Rate Curve From Time Zero to: 18h [AUER(0-18)] and 36h [AUER(0-36)] for UMEC
Ae(0-24)
|
2352.662 ng
Geometric Coefficient of Variation 47.5
|
5486.724 ng
Geometric Coefficient of Variation 48.3
|
12401.722 ng
Geometric Coefficient of Variation 33.7
|
—
|
—
|
|
Amount of Drug Excreted Unchanged in Urine From Time Zero to: 2h [Ae(0-2)] , 8h [Ae(0-8)], 12h [Ae(0-12)], 24h [Ae(0-24)], and 48h [Ae(0-48)]; and Area Under the Excretion Rate Curve From Time Zero to: 18h [AUER(0-18)] and 36h [AUER(0-36)] for UMEC
Ae(0-48)
|
2729.434 ng
Geometric Coefficient of Variation 45.0
|
6361.233 ng
Geometric Coefficient of Variation 47.0
|
13671.981 ng
Geometric Coefficient of Variation 34.7
|
—
|
—
|
|
Amount of Drug Excreted Unchanged in Urine From Time Zero to: 2h [Ae(0-2)] , 8h [Ae(0-8)], 12h [Ae(0-12)], 24h [Ae(0-24)], and 48h [Ae(0-48)]; and Area Under the Excretion Rate Curve From Time Zero to: 18h [AUER(0-18)] and 36h [AUER(0-36)] for UMEC
AUER(0-18)
|
2119.916 ng
Geometric Coefficient of Variation 48.4
|
4830.401 ng
Geometric Coefficient of Variation 47.9
|
10919.838 ng
Geometric Coefficient of Variation 34.6
|
—
|
—
|
|
Amount of Drug Excreted Unchanged in Urine From Time Zero to: 2h [Ae(0-2)] , 8h [Ae(0-8)], 12h [Ae(0-12)], 24h [Ae(0-24)], and 48h [Ae(0-48)]; and Area Under the Excretion Rate Curve From Time Zero to: 18h [AUER(0-18)] and 36h [AUER(0-36)] for UMEC
AUER(0-36)
|
2487.288 ng
Geometric Coefficient of Variation 48.8
|
5752.880 ng
Geometric Coefficient of Variation 49.3
|
12363.246 ng
Geometric Coefficient of Variation 35.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: PK Population
The CLr is defined as the apparent total clearance of the drug from plasma after oral administration. Blood samples for PK analysis of UMEC were obtained on Day 1at pre-dose and 5 minutes (min), 15 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, and 24 h post UMEC dose administration.
Outcome measures
| Measure |
Placebo
n=22 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Renal Clearance (CLr) of UMEC Following Dose Administration on Day 1
|
5.317 Liters per hour (L/hr)
Geometric Coefficient of Variation 56.2
|
6.395 Liters per hour (L/hr)
Geometric Coefficient of Variation 36.9
|
6.831 Liters per hour (L/hr)
Geometric Coefficient of Variation 56.8
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: PK Population
The terminal half-life (t1/2) of UMEC is defined as the time required for the urine concentration of UMEC to reach half of its original concentration. Urine samples for PK analysis of UMEC were obtained on Day 1; a single sample was collected at each of the following timepoints: 0-2 h, 2-8 h, 8-12 h, 12-24 h and 24-48 h post UMEC dose administration.
Outcome measures
| Measure |
Placebo
n=22 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Half-life for Renal Excretion of UMEC on Day 1
|
10.679 Hours
Geometric Coefficient of Variation 37.2
|
12.023 Hours
Geometric Coefficient of Variation 44.9
|
10.821 Hours
Geometric Coefficient of Variation 32.8
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: PK Population
Urine samples were collected to determine the urine concentrations of UMEC from 0 min up to 48 hours post-dose of each treatment period to derive Fe(0-24) and Fe(0-48). Urine samples for PK analysis of UMEC were obtained on Day 1; a single sample was collected at each of the following timepoints: 0-2 h, 2-8 h, 8-12 h, 12-24 h and 24-48 h post UMEC dose administration.
Outcome measures
| Measure |
Placebo
n=22 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Fraction of Dose Excreted Unchanged in Urine From Time Zero to: 24 Hours [Fe(0-24)] and 48 Hours [Fe(0-48)] for UMEC
Fe(0-24)
|
0.993 Percentage of total dose administered
Interval 0.32 to 2.56
|
1.253 Percentage of total dose administered
Interval 0.46 to 2.73
|
1.360 Percentage of total dose administered
Interval 0.68 to 1.94
|
—
|
—
|
|
Fraction of Dose Excreted Unchanged in Urine From Time Zero to: 24 Hours [Fe(0-24)] and 48 Hours [Fe(0-48)] for UMEC
Fe(0-48)
|
1.142 Percentage of total dose administered
Interval 0.42 to 2.88
|
1.413 Percentage of total dose administered
Interval 0.48 to 2.95
|
1.512 Percentage of total dose administered
Interval 0.77 to 2.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been summarized for different parameters/at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
Serial spirometry assessments were conducted on Day 1 of each treatment period over the course of 24 hours and were taken at 1 hour (h), 2 h, 6 h, 9 h, 12 h and 24 h post-dose. The maximum of the 3 FEV1 measurements for each participant, treatment period and timepoint were used in the calculation of the mean for each treatment group at each timepoint.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Mean Serial FEV1over 24 Hours After Dosing on Day 1 of Each Treatment Period
FEV1, 1 h, n= 21, 20, 21, 13, 8
|
1.638 Liters
Standard Error 0.0410
|
1.861 Liters
Standard Error 0.0437
|
1.915 Liters
Standard Error 0.0408
|
1.834 Liters
Standard Error 0.0542
|
1.880 Liters
Standard Error 0.0644
|
|
Mean Serial FEV1over 24 Hours After Dosing on Day 1 of Each Treatment Period
FEV1, 2h, n= 21, 20, 21, 13, 8
|
1.654 Liters
Standard Error 0.0433
|
1.951 Liters
Standard Error 0.0456
|
2.027 Liters
Standard Error 0.0431
|
1.992 Liters
Standard Error 0.0570
|
1.910 Liters
Standard Error 0.0684
|
|
Mean Serial FEV1over 24 Hours After Dosing on Day 1 of Each Treatment Period
FEV1, 6h, n=21, 22, 21, 13, 8
|
1.669 Liters
Standard Error 0.0497
|
1.991 Liters
Standard Error 0.0510
|
2.083 Liters
Standard Error 0.0492
|
2.070 Liters
Standard Error 0.0648
|
2.050 Liters
Standard Error 0.0793
|
|
Mean Serial FEV1over 24 Hours After Dosing on Day 1 of Each Treatment Period
FEV1, 9h, n=21, 19, 21, 13, 7
|
1.721 Liters
Standard Error 0.0418
|
1.938 Liters
Standard Error 0.0446
|
2.021 Liters
Standard Error 0.0416
|
2.024 Liters
Standard Error 0.0553
|
1.927 Liters
Standard Error 0.0673
|
|
Mean Serial FEV1over 24 Hours After Dosing on Day 1 of Each Treatment Period
FEV1, 12h, n=21, 22, 21, 13, 7
|
1.662 Liters
Standard Error 0.0501
|
1.917 Liters
Standard Error 0.0514
|
1.996 Liters
Standard Error 0.0497
|
1.988 Liters
Standard Error 0.0654
|
1.812 Liters
Standard Error 0.0801
|
|
Mean Serial FEV1over 24 Hours After Dosing on Day 1 of Each Treatment Period
FEV1, 24h, n=21, 22, 21, 13, 8
|
1.583 Liters
Standard Error 0.0411
|
1.818 Liters
Standard Error 0.0431
|
1.827 Liters
Standard Error 0.0410
|
1.856 Liters
Standard Error 0.0544
|
1.655 Liters
Standard Error 0.0646
|
SECONDARY outcome
Timeframe: Day 1 of each treatment period (up to Study Day 46)Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been summarized for different parameters/at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
sGaw is the specific airways resistance (mid) which was assessed by whole body plethysmography. Values used were the mean of the 3 readings recorded at each timepoint. sGaw measurements were taken at 2 hour (h), 6 h, 12 h and 24 h post-dose of each treatment period. 1/kPa.s=1(the inverses)/kPa (kilopascal).s (second)
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 micrograms (µg) via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 Participants
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 Participants
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Mean Serial Specific Airway Resistance (sGaw) Over 24 Hours After Dosing on Day 1 of Each Treatment Period
sGaw, 12h, n=21, 21, 21, 13, 8
|
0.403 1/kPa*s
Standard Error 0.0661
|
0.637 1/kPa*s
Standard Error 0.0692
|
0.735 1/kPa*s
Standard Error 0.0665
|
0.730 1/kPa*s
Standard Error 0.0836
|
0.550 1/kPa*s
Standard Error 0.1008
|
|
Mean Serial Specific Airway Resistance (sGaw) Over 24 Hours After Dosing on Day 1 of Each Treatment Period
sGaw, 24h, n=21, 21, 21, 13, 8
|
0.379 1/kPa*s
Standard Error 0.0627
|
0.514 1/kPa*s
Standard Error 0.0662
|
0.501 1/kPa*s
Standard Error 0.0630
|
0.514 1/kPa*s
Standard Error 0.0790
|
0.440 1/kPa*s
Standard Error 0.0945
|
|
Mean Serial Specific Airway Resistance (sGaw) Over 24 Hours After Dosing on Day 1 of Each Treatment Period
sGaw, 2h, n= 21, 20, 21, 13, 8
|
0.400 1/kPa*s
Standard Error 0.0598
|
0.652 1/kPa*s
Standard Error 0.0631
|
0.699 1/kPa*s
Standard Error 0.0602
|
0.714 1/kPa*s
Standard Error 0.0753
|
0.648 1/kPa*s
Standard Error 0.0893
|
|
Mean Serial Specific Airway Resistance (sGaw) Over 24 Hours After Dosing on Day 1 of Each Treatment Period
sGaw, 6h, n=21, 21, 21, 13, 8
|
0.426 1/kPa*s
Standard Error 0.0574
|
0.734 1/kPa*s
Standard Error 0.0603
|
0.806 1/kPa*s
Standard Error 0.0578
|
0.778 1/kPa*s
Standard Error 0.0720
|
0.711 1/kPa*s
Standard Error 0.0848
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
UMEC 250 µg
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
UMEC 500 µg
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
UMEC 1000 µg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Tiotropium 18 µg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=21 participants at risk
Participants received a single inhaled dose of matching placebo via a dry powder inhaler (DPI) in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 250 µg
n=22 participants at risk
Participants received a single inhaled dose of a dry powder formulation of UMEC 250 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 500 µg
n=21 participants at risk
Participants received a single inhaled dose of a dry powder formulation of UMEC 500 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
UMEC 1000 µg
n=13 participants at risk
Participants received a single inhaled dose of a dry powder formulation of UMEC 1000 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
Tiotropium 18 µg
n=8 participants at risk
Participants received a single inhaled dose of a dry powder formulation of tiotropium 18 µg via a DPI in one of the 4 treatment periods, separated by a washout period of at least 14 days.
|
|---|---|---|---|---|---|
|
Nervous system disorders
Headache
|
19.0%
4/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
18.2%
4/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
19.0%
4/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
7.7%
1/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Nervous system disorders
Dizziness
|
4.8%
1/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
9.5%
2/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
7.7%
1/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Nervous system disorders
Tension headache
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
4.5%
1/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Infections and infestations
Nasopharyngitis
|
4.8%
1/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
4.5%
1/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
4.5%
1/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
4.8%
1/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Infections and infestations
Urinary tract infection
|
4.8%
1/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
12.5%
1/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Infections and infestations
Infected insect bite
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
4.5%
1/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Infections and infestations
Sinusitis
|
4.8%
1/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
15.4%
2/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
4.8%
1/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
4.5%
1/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
12.5%
1/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
4.8%
1/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
7.7%
1/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
12.5%
1/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
4.8%
1/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
4.8%
1/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Gastrointestinal disorders
Gingivitis
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
4.5%
1/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Gastrointestinal disorders
Tooth loss
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
4.8%
1/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
4.5%
1/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
4.8%
1/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
7.7%
1/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
General disorders
Asthenia
|
4.8%
1/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gammopathy
|
4.8%
1/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/22 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/21 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/13 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received at least one dose of study medication.
|
0.00%
0/8 • Serious adverse events (SAEs) and non-serious AEs were collected from Day 1 of Treatment Period 1 until Follow-up visit (up to 10 weeks)
AEs and SAEs were collected in the members of All Subjects Population comprised of all participants who received 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