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A Study to Assess the Safety and Tolerability of Once Daily Inhaled Doses of GSK573719 Made With Magnesium Stearate in Subjects With Chronic Obstructive Pulmonary Disease(COPD)for 7 Days

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00732472
Recruitment Status : Completed
First Posted : August 12, 2008
Results First Posted : February 17, 2014
Last Update Posted : November 23, 2016
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Intervention Drug: GSK573719
Enrollment 37
Recruitment Details Participants=par.; umeclidinium=UMEC. A total of 37 unique par. were enrolled in the study; however, 1 par. was randomized and dosed on two separate occasions and is counted as two separate par. on all outputs (thus, 38 par. started study treatment).
Pre-assignment Details Participants were assigned to one of two cohorts: UMEC 250 micrograms (μg) once daily (QD) or placebo (Cohort 1) and UMEC 1000 μg QD or placebo (Cohort 2) for 7 days. After reporting of Cohorts 1 and 2, it was found that par. in Cohort 2 received UMEC 250 μg in error. Cohort 3 was then recruited, in which par. received UMEC 1000 μg QD or placebo.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI). Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI. Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error. Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Period Title: Overall Study
Started 9 10 [1] 10 9
Completed 9 7 9 6
Not Completed 0 3 1 3
Reason Not Completed
Adverse Event             0             1             1             1
Protocol Violation             0             0             0             1
Withdrawal by Subject             0             2             0             1
[1]
One par. (counted as 2 on outputs) was randomized/dosed with UMEC 250 µg on 2 separate occasions.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg Total
Hide Arm/Group Description Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI). Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI. Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error. Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI. Total of all reporting groups
Overall Number of Baseline Participants 9 10 10 9 38
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 10 participants 10 participants 9 participants 38 participants
66.2  (4.47) 63.3  (8.21) 64.7  (6.31) 64.2  (7.97) 64.6  (6.72)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 10 participants 10 participants 9 participants 38 participants
Female
4
  44.4%
4
  40.0%
2
  20.0%
4
  44.4%
14
  36.8%
Male
5
  55.6%
6
  60.0%
8
  80.0%
5
  55.6%
24
  63.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
White - White/Caucasian/European Heritage Number Analyzed 9 participants 10 participants 10 participants 9 participants 38 participants
9 10 10 9 38
1.Primary Outcome
Title Number of Participants With Any On-treatment Adverse Event (AE) or Any On-treatment Serious Adverse Event (SAE)
Hide Description An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An on-treatment adverse event is defined as an event that occurred between the start of investigational product and follow-up contact. Refer to the general SAE/non-serious AE module for a complete list of AEs reported in the study. 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, or is a congenital anomaly/birth defect.
Time Frame From start of treatment to study day 12
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population: all participants who received at least one dose of study medication
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 9 10 10 9
Measure Type: Number
Unit of Measure: participants
Any on-treatment AE 6 2 8 5
Any on-treatment SAE 0 0 0 0
2.Primary Outcome
Title Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) on Days 1 and 7
Hide Description Blood pressure was measured in a semi-recumbent position at approximately 45 degrees after the participant was kept at rest for at least 5 minutes. SBP and DBP were obtained at pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, and 8 hr post-dose (PD) on Day 1 and at pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr PD on Day 7.
Time Frame Day 1 (pre-dose and 15 minutes [min], 45 min, 1.5 hours [hr], 4 hr, and 8 hr post-dose) and Day 7 (pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population (ASP). Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 9 10 10 9
Mean (Standard Deviation)
Unit of Measure: Millimeters of mercury (mmHg)
SBP, Day 1, pre-dose, n=9, 10, 10, 9 138.9  (11.43) 132.8  (11.97) 137.4  (10.71) 138.6  (19.13)
SBP, Day 1, 15 min PD, n=9, 9, 10, 8 135.1  (12.96) 134.9  (15.05) 137.7  (9.94) 135.0  (14.72)
SBP, Day 1, 45 min PD, n=9, 9, 10, 9 133.3  (9.35) 135.8  (14.63) 133.9  (11.28) 140.1  (17.64)
SBP, Day 1, 1.5 hr PD, n=9, 9, 10, 9 140.0  (19.42) 138.2  (15.79) 142.1  (12.91) 145.0  (21.27)
SBP, Day 1, 4 hr PD, n=9, 9, 10, 9 141.0  (15.41) 139.4  (21.43) 141.6  (8.86) 138.9  (11.79)
SBP, Day 1, 8 hr PD, n=9, 9, 10, 9 134.8  (12.22) 135.7  (15.28) 140.8  (13.14) 146.2  (14.19)
SBP, Day 7, pre-dose, n=9, 7, 9, 6 134.3  (9.16) 131.8  (14.47) 139.3  (10.59) 120.2  (10.97)
SBP, Day 7, 15 min PD, n=9, 7, 9, 6 141.3  (13.95) 134.4  (15.54) 138.8  (12.67) 127.5  (14.29)
SBP, Day 7, 45 min PD, n=9, 7, 9, 6 139.7  (13.93) 135.4  (19.08) 135.8  (9.28) 126.3  (14.28)
SBP, Day 7, 1.5 hr PD, n=9, 7, 9, 6 137.8  (15.34) 141.6  (18.35) 141.3  (10.9) 130.2  (10.76)
SBP, Day 7, 4 hr PD, n=9, 7, 9, 6 139.4  (12.91) 139.6  (15.18) 141.6  (8.56) 135.0  (14.6)
SBP, Day 7, 8 hr PD, n=9, 7, 9, 6 136.1  (13.17) 129.4  (14.32) 136.1  (13.7) 125.7  (8.29)
SBP, Day 7, 24 hr PD, n=9, 7, 9, 6 132.1  (9.49) 135.7  (9.39) 136.0  (9.82) 127.5  (7.71)
DBP, Day 1, pre-dose, n=9, 10, 10, 9 81.6  (8.52) 79.0  (6.69) 82.1  (7.63) 82.4  (5.25)
DBP, Day 1, 15 min PD, n=9, 9, 10, 8 79.6  (9.76) 83.6  (7.47) 81.4  (7.71) 85.8  (10.46)
DBP, Day 1, 45 min PD, n=9, 9, 10, 9 78.9  (8.85) 79.6  (9.58) 82.8  (9.96) 83.8  (7.90)
DBP, Day 1, 1.5 hr PD, n=9, 9, 10, 9 79.3  (8.54) 82.3  (9.26) 84.0  (6.55) 85.4  (6.88)
DBP, Day 1, 4 hr PD, n=9, 9, 10, 9 83.4  (11.14) 81.0  (10.91) 83.1  (11.13) 83.7  (6.06)
DBP, Day 1, 8 hr PD, n=9, 9, 10, 9 77.8  (8.67) 79.9  (8.85) 80.5  (7.84) 85.3  (6.08)
DBP, Day 7, pre-dose, n=9, 7, 9, 6 78.7  (8.64) 82.6  (8.85) 85.8  (7.79) 76.5  (4.35)
DBP, Day 7, 15 min PD, n=9, 7, 9, 6 82.8  (11.78) 82.7  (9.11) 82.9  (9.29) 81.8  (5.46)
DBP, Day 7, 45 min PD, n=9, 7, 9, 6 80.6  (10.36) 81.4  (9.45) 82.4  (7.04) 81.8  (6.49)
DBP, Day 7, 1.5 hr PD, n=9, 7, 9, 6 82.2  (9.91) 82.6  (8.90) 83.1  (9.97) 81.7  (3.50)
DBP, Day 7, 4 hr PD, n=9, 7, 9, 6 79.0  (8.97) 84.0  (7.68) 83.0  (8.09) 81.0  (4.00)
DBP, Day 7, 8 hr PD, n=9, 7, 9, 6 76.2  (8.70) 77.1  (11.51) 80.7  (7.45) 77.8  (3.54)
DBP, Day 7, 24 hr PD, n=9, 7, 9, 6 78.2  (8.87) 81.6  (9.05) 81.7  (9.70) 79.8  (4.79)
3.Primary Outcome
Title Mean Heart Rate (HR) on Days 1 and 7
Hide Description HR was measured in a semi-recumbent position at approximately 45 degrees after the participant was kept at rest for at least 5 minutes. HR was obtained at pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, and 8 hr post-dose (PD) on Day 1 and at pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr PD on Day 7.
Time Frame Day 1 (pre-dose and 15 minutes [min], 45 min, 1.5 hours [hr], 4 hr, and 8 hr post-dose) and Day 7 (pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 9 10 10 9
Mean (Standard Deviation)
Unit of Measure: Beats per minute
Day 1, pre-dose, n=9, 10, 10, 9 70.9  (11.09) 68.3  (10.42) 72.8  (11.69) 64.7  (10.34)
Day 1, 15 min PD, n=9, 9, 10, 8 68.2  (10.28) 67.4  (11.28) 71.4  (9.86) 72.3  (13.56)
Day 1, 45 min PD, n=9, 9, 10, 9 66.0  (9.33) 62.3  (10.90) 70.2  (11.95) 66.4  (14.78)
Day 1, 1.5 hr PD, n=9, 9, 10, 9 63.3  (9.42) 60.7  (12.06) 65.8  (10.30) 64.2  (11.05)
Day 1, 4 hr PD, n=9, 9, 10, 9 64.0  (10.37) 62.0  (10.31) 70.2  (10.74) 65.7  (10.20)
Day 1, 8 hr PD, n=9, 9, 10, 9 72.6  (9.93) 67.4  (9.62) 77.2  (11.73) 74.4  (7.35)
Day 7, pre-dose, n=9, 7, 9, 6 70.1  (7.90) 71.3  (12.64) 71.4  (14.01) 69.7  (10.51)
Day 7, 15 min PD, n=9, 7, 9, 6 67.0  (6.61) 69.4  (12.16) 68.9  (12.19) 74.8  (9.39)
Day 7, 45 min PD, n=9, 6, 9, 6 66.8  (9.16) 66.3  (11.88) 66.6  (10.98) 70.0  (10.00)
Day 7, 1.5 hr PD, n=9, 7, 9, 6 65.3  (7.86) 64.0  (10.92) 63.8  (8.96) 67.7  (11.13)
Day 7, 4 hr PD, n=9, 7, 9, 6 64.1  (7.61) 62.7  (7.74) 62.6  (9.79) 67.5  (7.50)
Day 7, 8 hr PD, n=9, 7, 9, 6 74.8  (6.83) 71.0  (8.60) 74.8  (8.91) 73.8  (7.41)
Day 7, 24 hr PD, n=9, 7, 9, 6 73.8  (7.00) 75.6  (11.50) 72.6  (8.97) 70.8  (9.89)
4.Primary Outcome
Title Maximum and Weighted Mean (0-4 Hour) Heart Rate at Days 1 and 7
Hide Description Maximum heart rate (Max HR) and weighted mean (WM) from 0-4 hour on Days 1 and 7 were derived. Max HR (0-4 h) is defined as the maximum heart rate attained within 0-4 h. The weighted mean HR (0-4 h) was derived by calculating the area under the curve, and then dividing the value by the relevant time interval. Each of the maximum and weighted mean (0-4h) endpoints for heart rate, was statistically analyzed using a mixed effects model. The terms treatment, baseline, day and any relevant interactions were considered in the model. Least squares means are adjusted for treatment, Baseline, day, treatment by Baseline and Baseline by day interaction, where Baseline is defined as the mean of the three pre-dose assessments.
Time Frame Day 1 and Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population (ASP). The number of participants presented represent those with data available at the time point being presented; however, all participants in the ASP without missing covariate information are included in the analysis.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 9 10 10 9
Least Squares Mean (Standard Error)
Unit of Measure: Beats per minute
Day 1, Max HR, n=9, 10, 10, 9 68.30  (2.009) 70.56  (1.910) 71.57  (1.924) 75.79  (2.066)
Day 7, Max HR, n=9, 7, 9, 6 68.99  (1.917) 70.24  (2.203) 66.74  (1.964) 77.69  (2.398)
Day 1, WM, n=9, 9, 10, 9 63.84  (1.582) 63.62  (1.584) 66.17  (1.514) 70.00  (1.627)
Day 7, WM, n=9, 7, 9, 6 64.83  (1.682) 64.98  (1.874) 62.32  (1.698) 71.89  (2.026)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Cohort 1 UMEC 250 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.26
Confidence Interval (2-Sided) 95%
-3.39 to 7.91
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.777
Estimation Comments Day 1, Max HR
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Cohort 1 UMEC 250 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
-4.78 to 7.28
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.922
Estimation Comments Day 7, Max HR
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Cohort 2 UMEC 250 µg in Error
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.27
Confidence Interval (2-Sided) 95%
-2.37 to 8.91
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.772
Estimation Comments Day 1, Max HR
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Cohort 2 UMEC 250 µg in Error
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.25
Confidence Interval (2-Sided) 95%
-7.89 to 3.39
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.729
Estimation Comments Day 7, Max HR
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Cohort 3 UMEC 1000 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.49
Confidence Interval (2-Sided) 95%
1.59 to 13.39
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.899
Estimation Comments Day 1, Max HR
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Cohort 3 UMEC 1000 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 8.70
Confidence Interval (2-Sided) 95%
2.34 to 15.05
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.079
Estimation Comments Day 7, Max HR
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Cohort 1 UMEC 250 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-4.80 to 4.34
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.243
Estimation Comments Day 1, WM
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Cohort 1 UMEC 250 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
-5.09 to 5.40
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.520
Estimation Comments Day 7, WM
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Cohort 2 UMEC 250 µg in Error
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.33
Confidence Interval (2-Sided) 95%
-2.12 to 6.77
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.182
Estimation Comments Day 1, WM
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, Cohort 2 UMEC 250 µg in Error
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.51
Confidence Interval (2-Sided) 95%
-7.48 to 2.45
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.378
Estimation Comments Day 7, WM
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, Cohort 3 UMEC 1000 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.16
Confidence Interval (2-Sided) 95%
1.51 to 10.81
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.282
Estimation Comments Day 1, WM
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, Cohort 3 UMEC 1000 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.06
Confidence Interval (2-Sided) 95%
1.57 to 12.54
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.642
Estimation Comments Day 7, WM
5.Primary Outcome
Title Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Values on Days 1 and 7
Hide Description The number of participants with normal (NL), abnormal not clinically significant (Abn NCS), and abnormal clinically significant (Abn CS) ECG findings, as well as those with unavailable results (NA) at pre-dose (PD1, PD2, PD3), and 15 min, 45 min, 1.5 hr, 4 hr, and 8 hr post-dose (PD) on Day 1 and at pre-dose (PD1, PD2, PD3), and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr post-dose on Day 7 are reported. The following are of potential clinical importance: absolute QTc interval >450 milliseconds (msec); increase from Baseline QTc >60 msec; PR interval <110 and >220 msec; QRS interval <75 and >110 msec. Clinical significance was based on the medical and scientific judgement of the investigator or qualified designee.
Time Frame Day 1 (pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, and 8 hr post-dose) and Day 7 (pre-dose and 15 min, 45 min, 1.5 hr, 4 hr, 8 hr, and 24 hr)
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only participants with data available at the indicated time points were summarized.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 9 10 10 9
Measure Type: Number
Unit of Measure: Participants
Day 1, PD1, NL, n=9, 10, 10, 9 5 3 6 6
Day 1, PD1, Abn NCS, n=9, 10, 10, 9 4 7 4 3
Day 1, PD1, Abn CS, n=9, 10, 10, 9 0 0 0 0
Day 1, PD1, NA, n=9, 10, 10, 9 0 0 0 0
Day 1, PD2, NL, n=9, 10, 10, 9 5 3 5 5
Day 1, PD2, Abn NCS, n=9, 10, 10, 9 4 7 5 3
Day 1, PD2, Abn CS, n=9, 10, 10, 9 0 0 0 0
Day 1, PD2, NA, n=9, 10, 10, 9 0 0 0 1
Day 1, PD3, NL, n=9, 10, 10, 9 4 4 5 5
Day 1, PD3, Abn NCS, n=9, 10, 10, 9 5 6 5 3
Day 1, PD3, Abn CS, 9, 10, 10, 9 0 0 0 0
Day 1, PD3, NA, n=9, 10, 10, 9 0 0 0 1
Day 1, 15 min PD, NL, n=9, 9, 10, 9 4 3 7 6
Day 1, 15 min PD, Abn NCS, n=9, 9, 10, 9 5 6 3 3
Day 1, 15 min PD, Abn CS, n=9, 9, 10, 9 0 0 0 0
Day 1, 15 min PD, NA, n=9, 9, 10, 9 0 0 0 0
Day 1, 45 min PD, NL, n=9, 9, 10, 9 5 3 7 6
Day 1, 45 min PD, Abn NCS, n=9, 9, 10, 9 4 6 3 3
Day 1, 45 min PD, Abn CS, n=9, 9, 10, 9 0 0 0 0
Day 1, 45 min PD, NA, n=9, 9, 10, 9 0 0 0 0
Day 1, 1.5 hr PD, NL, n=9, 9, 10, 9 5 6 6 5
Day 1, 1.5 hr PD, Abn NCS, n=9, 9, 10, 9 4 3 4 4
Day 1, 1.5 hr PD, Abn CS, n=9, 9, 10, 9 0 0 0 0
Day 1, 1.5 hr PD, NA, n=9, 9, 10, 9 0 0 0 0
Day 1, 4 hr PD, NL, n=9, 9, 10, 9 4 4 6 5
Day 1, 4 hr PD, Abn NCS, n=9, 9, 10, 9 5 5 4 4
Day 1, 4 hr PD, Abn CS, n=9, 9, 10, 9 0 0 0 0
Day 1, 4 hr PD, NA, n=9, 9, 10, 9 0 0 0 0
Day 1, 8 hr PD, NL, n=9, 9, 10, 9 5 6 7 6
Day 1, 8 hr PD, Abn NCS, n=9, 9, 10, 9 4 3 3 3
Day 1, 8 hr PD, Abn CS, n=9, 9, 10, 9 0 0 0 0
Day 1, 8 hr PD, NA, n=9, 9, 10, 9 0 0 0 0
Day 7, PD1, NL, n=9, 7, 9, 6 4 4 7 3
Day 7, PD1, Abn NCS, n=9, 7, 9, 6 5 3 2 3
Day 7, PD1, Abn CS, n=9, 7, 9, 6 0 0 0 0
Day 7, PD1, NA, n=9, 7, 9, 6 0 0 0 0
Day 7, PD2, NL, n=9, 7, 8, 6 4 4 6 3
Day 7, PD2, Abn NCS, n=9, 7, 8, 6 5 3 2 3
Day 7, PD2, Abn CS, n=9, 7, 8, 6 0 0 0 0
Day 7, PD2, NA, n=9, 7, 8, 6 0 0 0 0
Day 7, PD3, NL, n=9, 7, 8, 6 4 3 6 3
Day 7, PD3, Abn NCS, n=9, 7, 8, 6 5 4 2 3
Day 7, PD3, Abn CS, 9, 7, 8, 6 0 0 0 0
Day 7, PD3, NA, n=9, 7, 8, 6 0 0 0 0
Day 7, 15 min PD, NL, n=9, 7, 9, 6 4 4 7 3
Day 7, 15 min PD, Abn NCS, n=9, 7, 9, 6 5 3 2 3
Day 7, 15 min PD, Abn CS, n=9, 7, 9, 6 0 0 0 0
Day 7, 15 min PD, NA, n=9, 7, 9, 6 0 0 0 0
Day 7, 45 min PD, NL, n=9, 7, 9, 6 4 4 6 3
Day 7, 45 min PD, Abn NCS, n=9, 7, 9, 6 5 3 3 3
Day 7, 45 min PD, Abn CS, n=9, 7, 9, 6 0 0 0 0
Day 7, 45 min PD, NA, n=9, 7, 9, 6 0 0 0 0
Day 7, 1.5 hr PD, NL, n=9, 7, 9, 6 4 4 7 3
Day 7, 1.5 hr PD, Abn NCS, n=9, 7, 9, 6 5 3 2 3
Day 7, 1.5 hr PD, Abn CS, n=9, 7, 9, 6 0 0 0 0
Day 7, 1.5 hr PD, NA, n=9, 7, 9, 6 0 0 0 0
Day 7, 4 hr PD, NL, n=9, 7, 9, 6 5 5 7 3
Day 7, 4 hr PD, Abn NCS, n=9, 7, 9, 6 4 2 2 3
Day 7, 4 hr PD, Abn CS, n=9, 7, 9, 6 0 0 0 0
Day 7, 4 hr PD, NA, n=9, 7, 9, 6 0 0 0 0
Day 7, 8 hr PD, NL, n=9, 7, 9, 6 4 4 7 3
Day 7, 8 hr PD, Abn NCS, n=9, 7, 9, 6 5 3 2 3
Day 7, 8 hr PD, Abn CS, n=9, 7, 9, 6 0 0 0 0
Day 7, 8 hr PD, NA, n=9, 7, 9, 6 0 0 0 0
Day 7, 24 hr PD, NL, n=9, 7, 9, 6 4 2 6 3
Day 7, 24 hr PD, Abn NCS, n=9, 7, 9, 6 5 5 3 3
Day 7, 24 hr PD, Abn CS, n=9, 7, 9, 6 0 0 0 0
Day 7, 24 hr PD, NA, n=9, 7, 9, 6 0 0 0 0
6.Primary Outcome
Title Number of Participants With Abnormal 24-hour Holter Findings at Screening and Day 7
Hide Description Twenty-four hour Holter ECG values were obtained at Screening and on Day 7. During the Screening procedure and study, standard Holter monitors were used (in order to exclude participants with underlying cardiac arrhythmogenicity). During the treatment periods, Holter monitors were only switched on immediately prior to dosing (up to 15 minutes pre-dose) so as to capture Holter ECG data from the 24 hour period following dosing. The following summary data were transcribed into the Case Report Form: Maximum and mean (0 to24 hour) heart rate; normal and aberrant beats and arrhythmias. Analysis of the Holter tapes was arranged by GlaxoSmithKline.The number of participants with normal (NL), abnormal not clinically significant (Abn NCS), and abnormal clinically significant (Abn CS) ECG findings, as well as those with unavailable results (NA) at Screening and Day 7, are reported. Clinical significance was based on the medical and scientific judgement of the investigator or qualified designee.
Time Frame Screening and Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only participants with data available at the indicated time points were summarized.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 9 10 10 9
Measure Type: Number
Unit of Measure: Participants
Screening, NL, n=9 ,10, 10, 9 2 6 5 3
Screening, Abn NCS, n=9 ,10, 10, 9 7 4 4 5
Screening, Abn CS, n=9 ,10, 10, 9 0 0 1 1
Day7, NL, n=9, 7, 9, 6 3 3 2 1
Day7, Abn NCS, n=9, 7, 9, 6 6 3 6 5
Day7, Abn CS, n=9, 7, 9, 6 0 0 1 0
Day7, NA, n=9, 7, 9, 6 0 1 0 0
7.Primary Outcome
Title Maximum and Mean (0-24 Hour) Heart Rate From Holter Monitoring on Day 7
Hide Description Maximum heart rate (Max HR) and mean HR from 0-24 hour Holter monitoring on treatment Day 7 were derived. The analysis was adjusted for treatment and Baseline, where Baseline is defined as the corresponding summary measure (i.e., mean heart rate [0-24 hours] or maximum heart rate [0-24 hours]) from screening records.
Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. The number of participants presented represent those with data available at the time point being presented; however, all participants in the ASP without missing covariate information are included in the analysis.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 9 6 9 6
Least Squares Mean (Standard Error)
Unit of Measure: Beats per minute
Max HR 125.19  (4.744) 134.08  (5.810) 127.48  (4.724) 126.91  (5.785)
Mean HR 77.47  (1.896) 75.94  (2.306) 75.96  (1.888) 76.75  (2.312)
8.Primary Outcome
Title Mean Forced Expiratory Volume in One Second (FEV1) at Screening and on Days 1 and 7
Hide Description FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured at Screening, pre-dose, and 4 hours (hr) post-dose on Day 1 and Day 7. FEV1 tests were repeated until three technically acceptable measurements were made.
Time Frame Screening, Day 1, and Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only participants with data available at the indicated time points were summarized.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 9 10 10 9
Mean (Standard Deviation)
Unit of Measure: Liters
Screening, n=9, 10, 10, 9 1.556  (0.6315) 1.253  (0.4338) 1.562  (0.5066) 1.364  (0.3504)
Day 1, pre-dose, n=9, 10, 10, 9 1.294  (0.4642) 1.059  (0.3509) 1.443  (0.4840) 1.289  (0.2968)
Day 1, 4 hr post-dose, n=9, 9, 10, 9 1.309  (0.4333) 1.250  (0.3934) 1.565  (0.5858) 1.534  (0.3389)
Day 7, pre-dose, n=9, 7, 9, 6 1.263  (0.4695) 1.153  (0.4066) 1.593  (0.5425) 1.483  (0.3055)
Day 7, 4 hr post-dose, n=9, 7, 9, 6 1.250  (0.5143) 1.181  (0.3875) 1.564  (0.5476) 1.517  (0.2685)
9.Primary Outcome
Title Total Number of Salbutamol Doses Taken Over the 7 -Day Study Period
Hide Description The total number of salbutamol doses taken per day was recorded by the participants in their dairy card over the entire 7-day treatment period. Diaries were reviewed by the Investigator when participants were admitted to the unit on Day 1, Day 7, and Day 8. Salbutamol was given as rescue medication, defined as a quick-relief or fast-acting medication that is given in addition to the investigational drug or placebo that can alleviate symptoms due to disease or lack of efficacy of the study treatment.
Time Frame Day 1 to Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only those participants who took at least one dose of salbutamol were summarized.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 6 3 5 5
Measure Type: Number
Unit of Measure: salbutamol doses
18 33 33 29
10.Primary Outcome
Title Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Concentration (MCHC) Values on Day 1 and Day 7
Hide Description Blood samples were collected for the measurement of albumin, total protein, hemoglobin, and MCHC values pre-dose on Day 1 and Day 7.
Time Frame Day 1 and Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 9 10 10 9
Mean (Standard Deviation)
Unit of Measure: Grams per liter (G/L)
Albumin, Day 1, n=9, 9, 10, 9 42.3  (3.43) 43.9  (2.09) 43.7  (2.16) 44.1  (3.10)
Albumin, Day 7, n=8, 7, 9, 6 43.1  (1.81) 44.0  (1.15) 43.8  (2.64) 44.0  (2.61)
Total protein, Day 1, n=9, 9, 10, 9 69.4  (5.48) 70.0  (3.24) 69.9  (3.70) 69.8  (3.46)
Total protein, Day 7, n=8, 7, 9, 6 68.6  (3.16) 70.0  (2.16) 71.0  (4.53) 69.7  (3.83)
Hemoglobin, Day 1, n=9, 9, 10, 9 152.2  (8.60) 148.0  (14.19) 147.4  (11.84) 145.4  (16.18)
Hemoglobin, Day 7, n=9, 6, 9, 6 151.4  (7.80) 145.8  (14.77) 147.4  (13.71) 143.5  (16.61)
MCHC, Day 1, n=9, 9, 10, 9 340.0  (6.10) 338.7  (5.39) 339.9  (5.49) 337.2  (3.63)
MCHC, Day 7, n=9, 6, 9, 6 337.6  (7.84) 340.7  (5.20) 337.4  (5.59) 337.3  (5.20)
11.Primary Outcome
Title Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Values on Day1 and Day 7
Hide Description Blood samples were collected for the measurement of ALP, ALT, AST, and GGT Pre-dose on Day 1 and Day 7.
Time Frame Day 1 and Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 9 10 10 9
Mean (Standard Deviation)
Unit of Measure: International units per liter (IU/L)
ALP, Day 1, n=9, 9, 10, 9 74.0  (20.20) 76.8  (15.11) 69.0  (18.43) 63.8  (20.00)
ALP, Day 7, n=8, 7, 9, 6 71.6  (20.18) 73.1  (16.16) 71.1  (16.47) 67.7  (18.15)
ALT, Day 1, n=9, 9, 10, 9 15.6  (10.36) 15.6  (6.06) 24.2  (9.66) 18.6  (9.49)
ALT, Day 7, n=8, 7, 9, 6 15.9  (6.85) 15.6  (7.11) 29.8  (12.81) 20.7  (9.85)
AST, Day 1, n=9, 9, 10, 9 20.9  (5.90) 18.9  (3.48) 26.5  (10.28) 22.6  (8.65)
AST, Day 7, n=8, 7, 9, 6 19.3  (6.16) 19.4  (4.31) 30.7  (12.16) 25.2  (8.18)
GGT, Day 1, n=9, 9, 10, 9 31.3  (20.62) 28.0  (13.19) 61.0  (56.20) 37.7  (31.25)
GGT, Day 7, n=8, 7, 9, 6 29.9  (18.88) 24.7  (6.78) 66.0  (68.81) 39.8  (32.73)
12.Primary Outcome
Title Direct Bilirubin, Total Bilirubin, and Creatinine Values on Day 1 and Day 7
Hide Description Blood samples were collected for the measurement of direct bilirubin, total bilirubin, and creatinine at pre-dose on Day 1 and Day 7.
Time Frame Day 1 and Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC19 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 9 10 10 9
Mean (Standard Deviation)
Unit of Measure: Micromoles per liter (µmol/L)
Direct bilirubin, Day 1, n=6, 9, 10 2.3  (1.97) 1.7  (0.50) 2.0  (1.15) NA [1]   (NA)
Direct bilirubin, Day 7, n=5, 7, 9 2.0  (1.41) 2.0  (0.58) 2.2  (0.67) NA [1]   (NA)
Total bilirubin, Day 1, n=9, 9, 10, 9 10.8  (4.44) 8.2  (1.20) 10.9  (4.01) 10.2  (3.03)
Total bilirubin, Day 7, n=8, 7, 9, 6 9.3  (4.03) 9.9  (2.27) 10.8  (3.11) 11.0  (3.16)
Creatinine, Day 1, n=9, 9, 10, 9 76.2  (12.15) 84.3  (15.64) 80.1  (14.26) 87.0  (33.59)
Creatinine, Day 7, n=8, 7, 9, 6 78.8  (10.53) 80.1  (14.37) 82.6  (12.83) 93.0  (39.80)
[1]
Per protocol, data were collected for participants in all 3 cohorts; however, Cohort 3 data were not fully reported to GSK by the vendor. This oversight was recently detected, and this summary will be amended once remedial work has been completed.
13.Primary Outcome
Title Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values on Day 1 and Day 7
Hide Description Blood samples were collected for the measurement of calcium, glucose, potassium, sodium, and urea/BUN pre-dose on Day 1 and Day 7.
Time Frame Day 1 and Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 9 10 10 9
Mean (Standard Deviation)
Unit of Measure: Millimoles per liter (mmol/L)
Calcium, Day 1, n=9, 9, 10, 9 2.317  (0.0622) 2.329  (0.0697) 2.342  (0.1215) 2.311  (0.0807)
Calcium, Day 7, n=8, 7, 9, 6 2.320  (0.0454) 2.321  (0.0308) 2.370  (0.1411) 2.343  (0.0631)
Glucose, Day 1, n=9, 9, 10, 9 5.16  (0.937) 5.13  (0.524) 5.38  (0.751) 5.26  (0.921)
Glucose, Day 7, n=8, 7, 9, 6 5.25  (0.746) 5.10  (0.792) 5.84  (0.948) 5.42  (0.717)
Potassium, Day 1, n=9, 9, 10, 9 4.67  (0.472) 4.70  (0.485) 4.50  (0.579) 4.36  (0.364)
Potassium, Day 7, n=8, 7, 9, 6 4.58  (0.276) 4.74  (0.431) 4.48  (0.519) 4.45  (0.428)
Sodium, Day 1, n=9, 9, 10, 9 138.8  (2.59) 140.6  (1.51) 140.6  (2.27) 139.6  (1.59)
Sodium, Day 7, n=8, 7, 9, 6 140.4  (2.88) 140.0  (1.15) 140.2  (2.44) 139.2  (2.40)
Urea/BUN, Day 1, n=9, 9, 10, 9 4.92  (1.730) 5.29  (0.842) 5.77  (1.854) 5.72  (2.440)
Urea/BUN, Day 7, n=8, 7, 9, 6 5.15  (1.032) 5.51  (0.691) 5.70  (1.562) 5.88  (3.020)
14.Primary Outcome
Title Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil (ANC: Absolute Neutrophil Count), Platelet, and White Blood Cell (WBC) Count Values on Day 1 and Day 7
Hide Description Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils (ANC), platelets, and white blood cell (WBC) count pre-dose on Day 1 and Day 7.
Time Frame Day 1 and Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 9 10 10 9
Mean (Standard Deviation)
Unit of Measure: 10^9 cells per liter (GI/L)
Basophils, Day 1, n=9, 9, 10, 9 NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Basophils, Day 7, n=9, 6, 9, 6 NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Eosinophils, Day 1, n=9, 9, 10, 9 0.248  (0.1052) 0.319  (0.1968) 0.352  (0.2951) 0.144  (0.0910)
Eosinophils, Day 7, n=9, 6, 9, 6 0.232  (0.0793) 0.280  (0.1754) 0.312  (0.2672) 0.153  (0.0911)
Lymphocytes, Day 1, n=9, 9, 10, 9 NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Lymphocytes, Day 7, n=9, 6, 9, 6 NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Monocytes, Day 1, n=9, 9, 10, 9 0.510  (0.1348) 0.614  (0.3648) 0.607  (0.1594) 0.506  (0.2010)
Monocytes, Day 7, n=9, 6, 9, 6 0.448  (0.1313) 0.562  (0.2791) 0.657  (0.1993) 0.503  (0.2430)
ANC, Day 1, n=9, 9, 10, 9 5.233  (2.0968) 5.306  (1.3061) 4.244  (1.3332) 4.946  (2.3879)
ANC, Day 7, n=9, 6, 9, 6 4.706  (1.8634) 5.023  (1.4969) 4.067  (1.0184) 5.323  (1.8539)
Platelets, Day 1, n=9, 9, 10, 9 278.1  (66.25) 238.2  (39.71) 254.7  (51.04) 222.4  (43.16)
Platelets, Day 7, n=9, 6, 9, 6 271.8  (53.73) 256.8  (36.71) 255.1  (61.42) 250.3  (59.37)
WBC count, Day 1, n=9, 9, 10, 9 8.06  (2.220) 8.52  (2.153) 7.11  (1.692) 7.56  (2.572)
WBC count, Day 7, n=9, 6, 9, 6 7.49  (2.211) 8.15  (2.519) 7.13  (1.564) 7.87  (2.067)
[1]
Per protocol, data were collected for participants in all 3 cohorts; however, data were not fully reported to GSK by the vendor. This oversight was recently detected, and this summary will be amended once remedial work has been completed.
15.Primary Outcome
Title Mean Corpuscle Hemoglobin (MCH) Values on Day 1 and Day 7
Hide Description Blood samples were collected for the measurement of MCH pre-dose on Day 1 and Day 7.
Time Frame Day 1 and Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 9 10 10 9
Mean (Standard Deviation)
Unit of Measure: picograms/cell (pg)
Day 1, n=9, 9, 10, 9 31.92  (1.711) 32.44  (2.371) 31.25  (1.978) 31.70  (1.859)
Day 7, n=9, 6, 9, 6 31.71  (1.661) 32.20  (2.871) 31.22  (1.999) 31.95  (2.146)
16.Primary Outcome
Title Mean Corpuscle Volume (MCV) Values on Day 1 and Day 7
Hide Description Blood samples were collected for the measurement of MCV pre-dose on Day 1 and Day 7.
Time Frame Day 1 and Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the ASP.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 9 10 10 9
Mean (Standard Deviation)
Unit of Measure: 10^-15 liters (femtoliters)
Day 1, n=9, 9, 10, 9 93.9  (3.66) 95.9  (7.06) 91.9  (4.93) 94.0  (5.32)
Day 7, n=9, 6, 9, 6 94.0  (3.50) 94.5  (7.12) 92.6  (5.34) 94.8  (5.49)
17.Secondary Outcome
Title Mean AUC(0-2), AUC(0-8), and AUC(0-t) of UMEC on Day 1 and Day 7
Hide Description Area under the concentration-time (AUC) curve from time zero (pre-dose) to 2 hours (AUC[0-2]), from time zero to 8 hours (AUC[0-8]), from time zero to the last time of a quantifiable concentration of UMEC (AUC[0-t]) on Day 1 and Day 7 were measured. AUC is a measure of systemic exposure. Blood samples were collected pre-dose and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose on Day 1 and Day 7. Also, a 24 hr blood sample was collected on Day 7.
Time Frame Day 1 and Day 7: pre-dose, and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose; 24 hr post-dose on Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) Population: participants (par.) in the ASP for whom a PK sample was obtained and analyzed. Different par. may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of par. summarized reflects everyone in the PK Population.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 0 8 9 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr * nanograms per milliliter (ng/mL)
AUC(0-2), Day 1, n=0, 8, 9, 9
0.19675
(19.7%)
0.08134
(108.0%)
0.95719
(233.2%)
AUC(0-2), Day 7, n=0, 6, 8, 6
0.31951
(51.6%)
0.15527
(66.5%)
1.92508
(31.1%)
AUC(0-8), Day 1, n=0, 0, 0, 9
NA [1] 
(NA%)
NA [1] 
(NA%)
2.029
(69.8%)
AUC(0-8), Day 7, n=0, 0, 0, 6
NA [1] 
(NA%)
NA [1] 
(NA%)
3.320
(33.3%)
AUC(0-t), Day 1, n=0, 8, 9, 9
0.26071
(39.1%)
0.03614
(1707.8%)
0.93299
(5820.5%)
AUC(0-t), Day 7, n=0, 6, 8, 6
0.55514
(113.2%)
0.30526
(134.3%)
4.86204
(42.8%)
[1]
Due to non-quantifiable data at the lower dose (250 µg) at later time points, data for this parameter could not be calculated.
18.Secondary Outcome
Title Cmax of UMEC on Day 1 and Day 7
Hide Description Cmax is defined as the maximum observed concentration of UMEC and was measured on Day 1 and Day 7. Blood samples were collected pre-dose and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose on Day 1 and Day 7. Also, a 24 hr blood sample was collected on Day 7.
Time Frame Day 1 and Day 7: pre-dose, and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose; 24 hr post-dose on Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only participants with data available at the indicated time points were summarized.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 0 8 9 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter (ng/mL)
Day 1, n=0, 8, 9, 9
0.21654
(32.0%)
0.07915
(147.6%)
1.52835
(53.6%)
Day 7, n=0, 6, 8, 6
0.33206
(58.3%)
0.16448
(74.2%)
2.75864
(60.5%)
19.Secondary Outcome
Title Tmax and Tlastof UMEC on Day 1 and Day 7
Hide Description Tmax is defined as the time to reach the observed maximum concentration, and tlast is defined as the time of the last quantifiable concentration of UMEC; both were measured on Day 1 and Day 7. Blood samples were collected pre-dose, and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose on Day 1 and Day 7. Also, a 24 hr blood sample was collected on Day 7.
Time Frame Day 1 and Day 7: pre-dose, and 5 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, and 8 hr post-dose; 24 hr post-dose on Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the PK Population.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 0 8 9 9
Median (Full Range)
Unit of Measure: hours
tmax, Day 1, n=0, 8, 8, 9
0.080
(0.08 to 0.50)
0.250
(0.08 to 0.28)
0.250
(0.08 to 0.28)
tmax, Day 7, n=0, 6, 8, 6
0.080
(0.02 to 0.25)
0.165
(0.08 to 0.32)
0.240
(0.07 to 0.25)
tlast, Day 1, n=0, 8, 8, 9
4.000
(2.00 to 8.12)
2.000
(0.08 to 4.00)
8.000
(0.08 to 8.00)
tlast, Day 7, n=0, 6, 8, 6
6.000
(2.00 to 27.05)
6.015
(2.00 to 24.00)
24.010
(24.00 to 24.48)
20.Secondary Outcome
Title Ae(0-4), Ae(0-8), Ae(0-12), and Ae(0-24) of UMEC on Day 1 and Day 7
Hide Description Urinary recovery of unchanged drug (UMEC) within the first 8, 12, and 24 hours (Ae[0-8], Ae[0-12], and Ae[0-24], respectively) on Day 1 and within the first 4, 8, 12, and 24 hours (Ae[0-4], Ae[0-8], Ae[0-12], and Ae[0-24], respectively) on Day 7 was estimated. Urine samples were collected from 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1 and from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7.
Time Frame From 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1; from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the PK Population.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 0 8 9 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms (ng)
Ae(0-4), Day 7, n=0, 5, 8, 6
1223.6
(77.8%)
669.5
(129.8%)
11854.5
(65.8%)
Ae(0-8), Day 1, n=0, 6, 7, 8
1756.0
(46.6%)
755.9
(101.5%)
13435.9
(53.8%)
Ae(0-8), Day 7, n=0, 5, 8, 6
3115.8
(27.2%)
1430.8
(49.6%)
19319.3
(50.5%)
Ae(0-12), Day 1, n=0, 6, 7, 8
2022.3
(41.2%)
921.7
(97.6%)
16069.2
(56.0%)
Ae(0-12), Day 7, n=0, 5, 8, 6
4165.6
(15.3%)
1960.5
(53.6%)
23496.1
(44.7%)
Ae(0-24), Day 1, n=0, 6, 7, 8
2503.5
(38.0%)
1420.3
(130.9%)
19552.7
(47.4%)
Ae(0-24), Day 7, n=0, 5, 8, 6
5606.2
(15.3%)
2984.5
(52.9%)
32140.0
(36.2%)
21.Secondary Outcome
Title Fe(0-4), Fe(0-8), Fe(0-12), and Fe(0-24) of UMEC on Day 1 and Day 7
Hide Description The fraction of the total dose excreted (Fe) in each interval was estimated as the urinary recovery of unchanged drug (Ae) per dose. Urine samples were collected from 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1 and from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7.
Time Frame From 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1; from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population: Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the PK Population.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 0 8 9 9
Mean (Standard Deviation)
Unit of Measure: Percentage of dose administered
Fe(0-4), Day 7, n=0, 5, 8, 6 0.58  (0.35) 0.37  (0.30) 1.35  (0.70)
Fe(0-8), Day 1, n=0, 6, 8, 8 0.76  (0.35) 0.34  (0.28) 1.49  (0.68)
Fe(0-8), Day 7, n=0, 5, 8, 6 1.28  (0.30) 0.62  (0.26) 2.10  (0.84)
Fe(0-12), Day 1, n=0, 6, 8, 8 0.87  (0.38) 0.41  (0.32) 1.78  (0.77)
Fe(0-12), Day 7, n=0, 5, 8, 6 1.68  (0.25) 0.86  (0.36) 2.52  (0.99)
Fe(0-24), Day 1, n=0, 6, 8, 8 1.06  (0.41) 0.70  (0.61) 2.12  (0.82)
Fe(0-24), Day 7, n=0, 5, 8, 6 2.26  (0.33) 1.31  (0.54) 3.38  (1.15)
22.Secondary Outcome
Title Renal Clearance of UMEC on Day 1 and Day 7
Hide Description Renal clearance was calculated as the urinary recovery of unchanged drug from time zero to time x (Ae[0-x])/area under concentration from time zero to time x (AUC[0-x]) for the longest period of time after dosing when both could be accurately determined (where x is either 8, 12, or 24). Urine samples were collected from 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1 and from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7.
Time Frame From 0-8 hours (hr), 8-12 hr, and 12-24 hr on Day 1; from 0-4 hr, 4-8 hr, 8-12 hr, and 12-24 hr on Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only participants with data available at the indicated time points were summarized. Different participants may have been summarized for different parameters/at different time points (reflected by n=X, X, X, X in the category titles), so the overall number of participants summarized reflects everyone in the PK Population.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 0 8 9 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liters/hour (L/hr)
Day 1, n=0, 1, 0, 8
6.5229 [1] 
(NA%)
NA [2] 
(NA%)
5.6173
(39.5%)
Day 7, n=0, 4, 6, 6
2.5923
(103.6%)
4.0826
(19.3%)
6.6104
(33.1%)
[1]
A dispersion cannot be calculated for a single participant.
[2]
Due to non-quantifiable data at the lower dose (250 µg) at later time points, data for this parameter could not be calculated.
23.Secondary Outcome
Title Urine Half Life (t1/2) of UMEC on Day 7
Hide Description Urine half life (t1/2) of UMEC on Day 7 was estimated. Urine samples were collected from 0-4 hours (hr), 4-8 hr, 8-12 hr, and 12-24 hr on Day 7.
Time Frame From 0-4 hours (hr), 4-8 hr, 8-12 hr, and 12-24 hr on Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only participants with data available at the indicated time points were summarized.
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description:
Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI).
Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI.
Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error.
Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
Overall Number of Participants Analyzed 0 2 4 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours
5.785
(39.4%)
8.299
(37.3%)
7.643
(33.4%)
Time Frame On-treatment serious adverse events (SAEs) and non-serious AEs (events occurring between the start of investigational product and follow-up contact) were collected from the start of study medication to the end of the treatment period (up to study day 12).
Adverse Event Reporting Description On-treatment SAEs and non-serious AEs were collected in members of the All Subjects Population, comprised of all participants who received at least one dose of study medication.
 
Arm/Group Title Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Hide Arm/Group Description Participants received either a single inhaled dose or four inhaled doses of matching placebo once daily (QD) for 7 days via a dry powder inhaler (DPI). Participants received a single inhaled dose of umeclidinium (UMEC) 250 micrograms (µg) formulated with magnesium stearate (MgSt) QD for 7 days via a DPI. Participants received a single inhaled dose of UMEC 250 μg formulated with MgSt QD for 7 days via a DPI. These participants were to have been randomized to receive UMEC 1000 µg; however, they received UMEC 250 µg in error. Participants received four inhaled doses of UMEC 250 μg (equivalent to 1000 μg) formulated with MgSt QD for 7 days via a DPI.
All-Cause Mortality
Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)   0/10 (0.00%)   0/10 (0.00%)   0/9 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo Cohort 1 UMEC 250 µg Cohort 2 UMEC 250 µg in Error Cohort 3 UMEC 1000 µg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/9 (66.67%)   2/10 (20.00%)   8/10 (80.00%)   5/9 (55.56%) 
Cardiac disorders         
Arrhythmia  1  0/9 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/9 (0.00%) 
Atrioventricular block second degree  1  0/9 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/9 (0.00%) 
Ear and labyrinth disorders         
Ear pain  1  1/9 (11.11%)  0/10 (0.00%)  0/10 (0.00%)  0/9 (0.00%) 
Gastrointestinal disorders         
Dry mouth  1  0/9 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/9 (11.11%) 
General disorders         
Thirst  1  0/9 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  2/9 (22.22%) 
Chest discomfort  1  1/9 (11.11%)  0/10 (0.00%)  0/10 (0.00%)  0/9 (0.00%) 
Chest pain  1  0/9 (0.00%)  1/10 (10.00%)  0/10 (0.00%)  0/9 (0.00%) 
Feeling abnormal  1  0/9 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/9 (11.11%) 
Infections and infestations         
Absess jaw  1  1/9 (11.11%)  0/10 (0.00%)  0/10 (0.00%)  0/9 (0.00%) 
Gastroenteritis  1  0/9 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/9 (11.11%) 
Lower respiratory tract infection  1  0/9 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/9 (11.11%) 
Respiratory tract infection  1  0/9 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/9 (0.00%) 
Rhinitis  1  0/9 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/9 (0.00%) 
Investigations         
Blood pressure increased  1  0/9 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  1/9 (11.11%) 
Blood glucose abnormal  1  0/9 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/9 (11.11%) 
Metabolism and nutrition disorders         
Decreased appetite  1  1/9 (11.11%)  0/10 (0.00%)  0/10 (0.00%)  0/9 (0.00%) 
Impaired fasting glucose  1  1/9 (11.11%)  0/10 (0.00%)  0/10 (0.00%)  0/9 (0.00%) 
Nervous system disorders         
Headache  1  1/9 (11.11%)  1/10 (10.00%)  4/10 (40.00%)  1/9 (11.11%) 
Dizziness  1  1/9 (11.11%)  0/10 (0.00%)  0/10 (0.00%)  0/9 (0.00%) 
Dysgeusia  1  0/9 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/9 (0.00%) 
Hypoaesthesia  1  1/9 (11.11%)  0/10 (0.00%)  0/10 (0.00%)  0/9 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  1/9 (11.11%)  0/10 (0.00%)  2/10 (20.00%)  0/9 (0.00%) 
Dyspnoea  1  2/9 (22.22%)  0/10 (0.00%)  0/10 (0.00%)  1/9 (11.11%) 
Bronchospasm  1  0/9 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/9 (0.00%) 
Oropharyngeal pain  1  0/9 (0.00%)  0/10 (0.00%)  0/10 (0.00%)  1/9 (11.11%) 
Skin and subcutaneous tissue disorders         
Pruritus  1  1/9 (11.11%)  0/10 (0.00%)  0/10 (0.00%)  0/9 (0.00%) 
Vascular disorders         
Flushing  1  1/9 (11.11%)  0/10 (0.00%)  0/10 (0.00%)  0/9 (0.00%) 
Hypertension  1  0/9 (0.00%)  0/10 (0.00%)  1/10 (10.00%)  0/9 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Subject 303 and Subject 317 correspond to the same participant who was randomized and dosed on two separate occasions. This participant has been counted as two separate participants on all the outputs.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
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Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00732472    
Other Study ID Numbers: 105211
First Submitted: August 11, 2008
First Posted: August 12, 2008
Results First Submitted: January 2, 2014
Results First Posted: February 17, 2014
Last Update Posted: November 23, 2016