GSK573719 Dose Ranging Study in Chronic Obstructive Pulmo... | NCT00950807 | Trialant
NCT00950807
Sponsor
GlaxoSmithKline
Status
Completed
Last Update Posted
Nov 8, 2017Actual
Enrollment
176Actual
Phase
Phase 2
Conditions
Pulmonary Disease, Chronic Obstructive
Interventions
Tiotropium
Placebo
GSK573179
Countries
United States
Germany
Protocol Section
Identification Module
NCT ID
NCT00950807
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
113073
Secondary IDs
Not provided
Brief Title
GSK573719 Dose Ranging Study in Chronic Obstructive Pulmonary Disease
Official Title
A Randomized, Double-Blind, Placebo-Controlled, 3-Way Cross-Over Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of GSK573719 Administered Once- and Twice-Daily in Subjects With COPD
Acronym
Not provided
Organization
GlaxoSmithKlineINDUSTRY
Status Module
Record Verification Date
Oct 2017
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Sep 1, 2009
Primary Completion Date
Mar 1, 2010Actual
Completion Date
Mar 15, 2010Actual
First Submitted Date
Jul 30, 2009
First Submission Date that Met QC Criteria
Jul 30, 2009
First Posted Date
Aug 3, 2009Estimated
Results Waived
Not provided
Results First Submitted Date
Jan 16, 2014
Results First Submitted that Met QC Criteria
Jan 16, 2014
Results First Posted Date
Mar 4, 2014Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Mar 22, 2012
Certification/Extension First Submitted that Passed QC Review
Mar 22, 2012
Certification/Extension First Posted Date
Mar 29, 2012Estimated
Last Update Submitted Date
Oct 9, 2017
Last Update Posted Date
Nov 8, 2017Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
GlaxoSmithKlineINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The study will evaluate the dose response, safety, and pharmacokinetics of GSK573719 compared with placebo in subjects with COPD.
Detailed Description
This is multicenter, randomized, double-blind, double-dummy, placebo-controlled, three-way cross-over, incomplete block design study to evaluation of 5 doses of GSK573719 administered once-daily and 3 doses of GSK573719 administered twice-daily over 14 days in subjects with COPD and will include tiotropium as an open-label active control. The pharmacokinetic profile of GSK573719 will also be evaluated.
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on Treatment Day 15 is defined as the value obtained 24 hours after the morning dose administered on Day 14. Analysis were performed using a mixed model with covariates of mean Baseline, period Baseline, treatment and period as fixed effects and participant as a random effect. Baseline is the FEV1 value recorded pre-dose on Day 1 of each treatment period; mean Baseline is the mean of the Baselines for each participant and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline for each treatment period is the trough FEV1 at Day 15 minus the Baseline value for that treatment period.
Baseline and Day 15 of each treatment period (up to Study Day 71)
Secondary Outcomes
Measure
Description
Time Frame
Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The weighted mean FEV1 was derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The weighted mean FEV1 was calculated using 0-24 hour (h) post-dose measurements at Day 14 of each treatment period, which included pre-dose and post-dose 1, 3, 6, 9, 12, 13, 15, 18, 21 and 24 hours. Analysis performed using a mixed model with covariates mean BL, period BL, treatment and period as fixed effects and participant as a random effect. BL is the FEV1 value recorded pre-dose on Day 1 of each TP; mean BL is the mean of the BLs for each participant and period BL is the difference between the BL and the mean BL in each TP for each participant. Change from BL for each TP is the trough FEV1 at Day 15 minus the BL value for that TP.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
A signed and dated written informed consent prior to study participation
Males or females of non-childbearing potential
40 to 80 years of age
COPD diagnosis
10 pack-years history or greater of cigarette smoking
Post-bronchodilator FEV1/FVC ratio of 0.70 or less
Post-bronchodilator FEV1 of 35 to 70% of predicted normal
Exclusion Criteria:
Asthma
Other significant respiratory disorders besides COPD, including alpha-1 deficiency
Previous lung resection surgery
Use of oral steroids or antibiotics for a COPD exacerbation within 6 weeks of screening
Hospitalization for COPD or pneumonia within 3 months of screening
Any significant disease that would put subject at risk through study participation
BMI greater than 35
Pacemaker
Significantly abnormal ECG, Holter, or clinical lab finding (including Hepatitis B or C)
Cancer
Allergy or hypersensitivity to anticholinergics or inhaler excipients
Diseases that would contra-indicate the use of anticholinergics
Use of oral corticosteroids within 6 weeks of screening
Use of long-acting beta-agonists within 48 hours of screening
Use of tiotropium within 14 days of screening
Use of theophyllines or anti-leukotrienes within 48 hours of screening
Use of short-acting bronchodilators within 4 to 6 hours of screening
Use of investigational medicines within 30 days of screening
Donohue JF, Anzueto A, Brooks J, Mehta R, Kalberg C, Crater G. A randomized, double-blind dose-ranging study of the novel LAMA GSK573719 in patients with COPD. Respir Med. 2012 Jul;106(7):970-9. doi: 10.1016/j.rmed.2012.03.012. Epub 2012 Apr 10.
See Also Links
Label
URL
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Participants (par.) who were eligible completed a 4- to 7-day Run-in period prior to randomization. The treatment (trt) phase was comprised of three 14-day trt periods. Par. were randomly assigned to receive a sequence of placebo and 2 of the 9 active trts over the trt phase. Participant Flow data are presented by treatment rather than sequence.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Placebo
Participants received matching placebo in the morning via dry powder inhaler (DPI) A and in the evening via DPI B for 14 days.
FG001
UMEC 62.5 µg QD
Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg) in the morning via DPI A and placebo in the evening via DPI B for 14 days.
Baseline and Day 14 of each treatment period (TP; up to Study Day 70)
Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period
Serial FEV1 for OQ dosing is recorded at the pre-AM dose (time 0 h) and at 1, 3, 6, 9, 12,13, 15, 18, 21, 24 and 28 hs after the AM dose on D 14. For BID dosing, the 12 h AM dose corresponds to the pre-PM dose, 13 h AM dose corresponds to the 1 h PM dose, 15 h AM dose corresponds to the 3 h PM dose, 18 h AM corresponds to the 6 h PM dose, 21 h AM dose corresponds to 9 h PM dose, 24 h AM dose corresponds to the 12 h PM dose and 28 h AM dose corresponds to the 16 h PM dose in the table. Analysis performed using a mixed model with covariates of mean BL, period BL, trt, period, time, time by period BL interaction, time by mean BL interaction and time by trt interaction as fixed effects and par. as a random effect. BL is the FEV1 value recorded pre-dose on D 1 of each TP; mean BL is the mean of the BLs for each par. and period BL is the difference between the BL and the mean BL in each TP for each par. Change from BL for each TP is the trough FEV1 at Day 15 minus the BL value for that TP.
Baseline and Day (D) 14 of each treatment period (TP; up to Study Day 70)
San Diego
California
92117
United States
GSK Investigational Site
Upland
California
91786
United States
GSK Investigational Site
Cincinnati
Ohio
45231
United States
GSK Investigational Site
Easley
South Carolina
29640
United States
GSK Investigational Site
Gaffney
South Carolina
29340
United States
GSK Investigational Site
Greenville
South Carolina
29615
United States
GSK Investigational Site
Seneca
South Carolina
29678
United States
GSK Investigational Site
Spartanburg
South Carolina
29303
United States
GSK Investigational Site
Union
South Carolina
29379
United States
GSK Investigational Site
Frankfurt am Main
Hesse
60596
Germany
GSK Investigational Site
Wiesbaden
Hesse
65187
Germany
GSK Investigational Site
Hanover
Lower Saxony
30159
Germany
GSK Investigational Site
Mainz
Rhineland-Palatinate
55131
Germany
GSK Investigational Site
Magdeburg
Saxony-Anhalt
39112
Germany
GSK Investigational Site
Großhansdorf
Schleswig-Holstein
22927
Germany
GSK Investigational Site
Berlin
10787
Germany
GSK Investigational Site
Berlin
13125
Germany
GSK Investigational Site
Hamburg
20253
Germany
For additional information about this study please refer to the GSK Clinical Study Register
For additional information about this study please refer to the GSK Clinical Study Register
FG002
UMEC 125 µg QD
Participants received UMEC 125 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
FG003
UMEC 250 µg QD
Participants received UMEC 250 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
FG004
UMEC 500 µg QD
Participants received UMEC 500 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
FG005
UMEC 1000 µg QD
Participants received UMEC 1000 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
FG006
UMEC 62.5 µg BID
Participants received UMEC 62.5 µg in the morning via DPI A and in the evening via DPI B for 14 days.
FG007
UMEC 125 µg BID
Participants received UMEC 125 µg in the morning via DPI A and in the evening via DPI B for 14 days.
FG008
UMEC 250 µg BID
Participants received UMEC 250 µg in the morning via DPI A and in the evening via DPI B for 14 days.
FG009
Tiotropium 18 µg QD
Participants received tiotropium bromide 18 µg in the morning via the HandiHaler and placebo in the evening via DPI B for 14 days.
FG00059 subjects
FG00113 subjects
FG00214 subjects
FG00312 subjects
FG00413 subjects
FG00513 subjects
FG00612 subjects
FG00714 subjects
FG00813 subjects
FG00913 subjects
COMPLETED
FG00056 subjects
FG00113 subjects
FG00213 subjects
FG00312 subjects
FG00412 subjects
FG00511 subjects
FG00612 subjects
FG00714 subjects
FG00812 subjects
FG00913 subjects
NOT COMPLETED
FG0003 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG0041 subjects
FG0052 subjects
FG0060 subjects
FG0070 subjects
FG0081 subjects
FG0090 subjects
Type
Comment
Reasons
Lack of Efficacy
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0051 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
Protocol Violation
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Washout Period 1
Type
Comment
Milestone Data
STARTED
FG00056 subjects
FG00113 subjects
FG00213 subjects
FG00312 subjects
FG00412 subjects
FG00511 subjects
FG00612 subjects
FG00714 subjects
FG00812 subjects
FG00913 subjects
COMPLETED
FG00051 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
FG00113 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
FG00213 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
FG003
NOT COMPLETED
FG0005 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Type
Comment
Reasons
Lack of Efficacy
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Treatment Period 2
Type
Comment
Milestone Data
STARTED
FG00053 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG00113 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG00210 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG00313 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG00413 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG00510 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG00610 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG00713 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG00811 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG00911 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
COMPLETED
FG00051 subjects
FG00112 subjects
FG00210 subjects
FG00312 subjects
FG004
NOT COMPLETED
FG0002 subjects
FG0011 subjects
FG0020 subjects
FG0031 subjects
FG004
Type
Comment
Reasons
Lack of Efficacy
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG003
Washout Period 2
Type
Comment
Milestone Data
STARTED
FG00051 subjects
FG00112 subjects
FG00210 subjects
FG00312 subjects
FG00413 subjects
FG0059 subjects
FG0069 subjects
FG00710 subjects
FG00811 subjects
FG00911 subjects
COMPLETED
FG00047 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
FG00111 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
FG00210 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
FG003
NOT COMPLETED
FG0004 subjects
FG0011 subjects
FG0020 subjects
FG0031 subjects
FG004
Type
Comment
Reasons
Lack of Efficacy
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG003
Treatment Period 3
Type
Comment
Milestone Data
STARTED
FG00046 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG0019 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG00210 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG00311 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG00412 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG0059 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG00612 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG00710 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG0089 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
FG00911 subjectsBy crossover design, participants were assigned to a different treatment arm in each period.
COMPLETED
FG00045 subjects
FG0019 subjects
FG00210 subjects
FG00311 subjects
FG004
NOT COMPLETED
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
All Study Treatments
The treatment phase was comprised of three 14-day treatment periods, each separated by a 10-14 day washout period. Participants were randomly assigned to receive a sequence of placebo and 2 of the 9 active treatments :
UMEC 62.5, 125, 250, 500, and 1000 µg QD, UMEC 62.5, 125, and 250 µg BID, tiotropium 18 µg QD.
Denominators
Units
Counts
Participants
BG000176
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00059.7± 8.12
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00075
Male
BG000101
Race/Ethnicity, Customized
Number
Participants
Title
Denominators
Categories
African American/African Heritage
Title
Measurements
BG0004
White
Title
Measurements
BG000
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 15 of Each Treatment Period
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on Treatment Day 15 is defined as the value obtained 24 hours after the morning dose administered on Day 14. Analysis were performed using a mixed model with covariates of mean Baseline, period Baseline, treatment and period as fixed effects and participant as a random effect. Baseline is the FEV1 value recorded pre-dose on Day 1 of each treatment period; mean Baseline is the mean of the Baselines for each participant and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline for each treatment period is the trough FEV1 at Day 15 minus the Baseline value for that treatment period.
Modified Intent-To-Treat (mITT) Population: all participants randomized to treatment who received at least one dose of study medication. 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 15.
Posted
Least Squares Mean
Standard Error
Liters
Baseline and Day 15 of each treatment period (up to Study Day 71)
ID
Title
Description
OG000
Placebo
Participants received matching placebo in the morning via dry powder inhaler (DPI) A and in the evening via DPI B for 14 days.
OG001
UMEC 62.5 µg QD
Participants received UMEC 62.5 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
OG002
UMEC 125 µg QD
Participants received UMEC 125 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
OG003
UMEC 250 µg QD
Participants received UMEC 250 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
OG004
UMEC 500 µg QD
Participants received UMEC 500 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
OG005
UMEC 1000 µg QD
Participants received UMEC 1000 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
OG006
UMEC 62.5 µg BID
Participants received UMEC 62.5 µg in the morning via DPI A and in the evening via DPI B for 14 days.
OG007
UMEC 125 µg BID
Units
Counts
Participants
OG000150
OG00134
OG00233
OG003
Title
Denominators
Categories
Title
Measurements
OG000-0.047± 0.017
OG0010.081± 0.033
OG0020.099± 0.034
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Mixed Models Analysis
<0.001
Mean Difference (Final Values)
0.128
2-Sided
95
0.060
0.196
Superiority or Other
OG000
OG002
Mixed Models Analysis
<0.001
Secondary
Change From Baseline (BL) in Weighted Mean FEV1 Over 0 to 24 Hours Obtained Post-dose on Day 14 of Each Treatment Period
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The weighted mean FEV1 was derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The weighted mean FEV1 was calculated using 0-24 hour (h) post-dose measurements at Day 14 of each treatment period, which included pre-dose and post-dose 1, 3, 6, 9, 12, 13, 15, 18, 21 and 24 hours. Analysis performed using a mixed model with covariates mean BL, period BL, treatment and period as fixed effects and participant as a random effect. BL is the FEV1 value recorded pre-dose on Day 1 of each TP; mean BL is the mean of the BLs for each participant and period BL is the difference between the BL and the mean BL in each TP for each participant. Change from BL for each TP is the trough FEV1 at Day 15 minus the BL value for that TP.
mITT 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 14.
Posted
Least Squares Mean
Standard Error
Liters
Baseline and Day 14 of each treatment period (TP; up to Study Day 70)
ID
Title
Description
OG000
Placebo
Participants received matching placebo in the morning via dry powder inhaler (DPI) A and in the evening via DPI B for 14 days.
OG001
Secondary
Change From Baseline (BL) in Serial FEV1 Over 0-28 Hours After the Morning Dose at Day 14 of Each Treatment Period
Serial FEV1 for OQ dosing is recorded at the pre-AM dose (time 0 h) and at 1, 3, 6, 9, 12,13, 15, 18, 21, 24 and 28 hs after the AM dose on D 14. For BID dosing, the 12 h AM dose corresponds to the pre-PM dose, 13 h AM dose corresponds to the 1 h PM dose, 15 h AM dose corresponds to the 3 h PM dose, 18 h AM corresponds to the 6 h PM dose, 21 h AM dose corresponds to 9 h PM dose, 24 h AM dose corresponds to the 12 h PM dose and 28 h AM dose corresponds to the 16 h PM dose in the table. Analysis performed using a mixed model with covariates of mean BL, period BL, trt, period, time, time by period BL interaction, time by mean BL interaction and time by trt interaction as fixed effects and par. as a random effect. BL is the FEV1 value recorded pre-dose on D 1 of each TP; mean BL is the mean of the BLs for each par. and period BL is the difference between the BL and the mean BL in each TP for each par. Change from BL for each TP is the trough FEV1 at Day 15 minus the BL value for that TP.
mITT Population. All par. with >=1 post-BL assessment and non-missing covariate data are included in the analysis. Different par. may have been analyzed at different time points (n=X, X, X, X in the category titles), so the overall number of par. analyzed reflects everyone in the mITT Population with data available at >=1 time point.
Posted
Mean
Standard Deviation
Liters
Baseline and Day (D) 14 of each treatment period (TP; up to Study Day 70)
ID
Title
Description
OG000
Placebo
Participants received matching placebo in the morning via dry powder inhaler (DPI) A and in the evening via DPI B for 14 days.
Time Frame
On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication up to 10 weeks.
Description
On-treatment AEs and non-serious AEs are reported for members of the mITT Population, comprised of all participants who were randomized to treatment and who had received at least one dose of randomized study medication during treatment period.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Placebo
Participants received matching placebo in the morning via dry powder inhaler (DPI) A and in the evening via DPI B for 14 days.
0
158
11
158
EG001
UMEC 62.5 µg QD
Participants received UMEC 62.5 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
0
35
2
35
EG002
UMEC 125 µg QD
Participants received UMEC 125 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
0
34
3
34
EG003
UMEC 250 µg QD
Participants received UMEC 250 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
2
36
8
36
EG004
UMEC 500 µg QD
Participants received UMEC 500 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
0
38
9
38
EG005
UMEC 1000 µg QD
Participants received UMEC 1000 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
0
32
13
32
EG006
UMEC 62.5 µg BID
Participants received UMEC 62.5 µg in the morning via DPI A and in the evening via DPI B for 14 days.
0
34
4
34
EG007
UMEC 125 µg BID
Participants received UMEC 125 µg in the morning via DPI A and in the evening via DPI B for 14 days.
1
37
4
37
EG008
UMEC 250 µg BID
Participants received UMEC 250 µg in the morning via DPI A and in the evening via DPI B for 14 days.
0
33
10
33
EG009
Tio 18 µg QD
Participants received tiotropium bromide 18 µg in the morning via the HandiHaler and placebo in the evening via DPI B for 14 days.
0
35
3
35
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Chronic obstructive pulmonary disease
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG0031 affected36 at risk
EG004
Concussion
Injury, poisoning and procedural complications
MedDRA
Systematic Assessment
EG0000 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0001 affected158 at risk
EG0011 affected35 at risk
EG0020 affected34 at risk
EG0031 affected36 at risk
EG0044 affected38 at risk
EG0052 affected32 at risk
EG0060 affected34 at risk
EG0070 affected37 at risk
EG0082 affected33 at risk
EG0090 affected35 at risk
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0002 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Dysphonia
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0001 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0001 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Rhinitis allergic
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0001 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Chronic obstructive pulmonary disease
Respiratory, thoracic and mediastinal disorders
MedDRA
Systematic Assessment
EG0000 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Headache
Nervous system disorders
MedDRA
Systematic Assessment
EG0004 affected158 at risk
EG0011 affected35 at risk
EG0021 affected34 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA
Systematic Assessment
EG0000 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Migraine
Nervous system disorders
MedDRA
Systematic Assessment
EG0000 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA
Systematic Assessment
EG0002 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Cystitis
Infections and infestations
MedDRA
Systematic Assessment
EG0000 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA
Systematic Assessment
EG0001 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA
Systematic Assessment
EG0001 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA
Systematic Assessment
EG0000 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Hypertension
Vascular disorders
MedDRA
Systematic Assessment
EG0000 affected158 at risk
EG0010 affected35 at risk
EG0022 affected34 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA
Systematic Assessment
EG0000 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA
Systematic Assessment
EG0000 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Thrombocytosis
Blood and lymphatic system disorders
MedDRA
Systematic Assessment
EG0000 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Joint sprain
Injury, poisoning and procedural complications
MedDRA
Systematic Assessment
EG0000 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Blood potassium increased
Investigations
MedDRA
Systematic Assessment
EG0000 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA
Systematic Assessment
EG0000 affected158 at risk
EG0010 affected35 at risk
EG0020 affected34 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
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.
Point of Contact
Title
Organization
Phone
Extension
Email
GSK Response Center
GlaxoSmithKline
866-435-7343
ID
Term
D029424
Pulmonary Disease, Chronic Obstructive
D029481
Bronchitis, Chronic
D004646
Emphysema
Ancestor Terms
ID
Term
D008173
Lung Diseases, Obstructive
D008171
Lung Diseases
D012140
Respiratory Tract Diseases
D002908
Chronic Disease
D020969
Disease Attributes
D010335
Pathologic Processes
D013568
Pathological Conditions, Signs and Symptoms
D001991
Bronchitis
D012141
Respiratory Tract Infections
D007239
Infections
D001982
Bronchial Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
D000069447
Tiotropium Bromide
Ancestor Terms
ID
Term
D012602
Scopolamine Derivatives
D014326
Tropanes
D053961
Azabicyclo Compounds
D001372
Aza Compounds
D009930
Organic Chemicals
D000470
Alkaloids
D006571
Heterocyclic Compounds
D019086
Bridged Bicyclo Compounds, Heterocyclic
D006572
Heterocyclic Compounds, Bridged-Ring
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
1 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0081 subjects
FG0090 subjects
0 subjects
FG0051 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
11 subjects
Participants withdrawing during washout are counted under the last treatment taken.
FG00411 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
FG00511 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
FG00610 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
FG00713 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
FG00811 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
FG00913 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
1 subjects
FG0050 subjects
FG0062 subjects
FG0071 subjects
FG0081 subjects
FG0090 subjects
0 subjects
FG0040 subjects
FG0050 subjects
FG0061 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0081 subjects
FG0090 subjects
Protocol-defined Stopping Criteria
FG0003 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0061 subjects
FG0071 subjects
FG0080 subjects
FG0090 subjects
Adverse Event
FG0002 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0041 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
13 subjects
FG0059 subjects
FG0069 subjects
FG00710 subjects
FG00811 subjects
FG00911 subjects
0 subjects
FG0051 subjects
FG0061 subjects
FG0073 subjects
FG0080 subjects
FG0090 subjects
0 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0061 subjects
FG0072 subjects
FG0080 subjects
FG0090 subjects
Protocol-defined Stopping Criteria
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
Adverse Event
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0051 subjects
FG0060 subjects
FG0071 subjects
FG0080 subjects
FG0090 subjects
11 subjects
Participants withdrawing during washout are counted under the last treatment taken.
FG00412 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
FG0059 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
FG0068 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
FG0079 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
FG00811 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
FG00911 subjectsParticipants withdrawing during washout are counted under the last treatment taken.
1 subjects
FG0050 subjects
FG0061 subjects
FG0071 subjects
FG0080 subjects
FG0090 subjects
0 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
Protocol-defined Stopping Criteria
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
FG0061 subjects
FG0071 subjects
FG0080 subjects
FG0090 subjects
Adverse Event
FG0003 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
12 subjects
FG0059 subjects
FG00611 subjects
FG0079 subjects
FG0089 subjects
FG00910 subjects
0 subjects
FG0050 subjects
FG0061 subjects
FG0071 subjects
FG0080 subjects
FG0091 subjects
0 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0091 subjects
Protocol-defined Stopping Criteria
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0071 subjects
FG0080 subjects
FG0090 subjects
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0061 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
172
Participants received UMEC 125 µg in the morning via DPI A and in the evening via DPI B for 14 days.
OG008
UMEC 250 µg BID
Participants received UMEC 250 µg in the morning via DPI A and in the evening via DPI B for 14 days.
OG009
Tio 18 µg QD
Participants received tiotropium bromide 18 µg in the morning via the HandiHaler and placebo in the evening via DPI B for 14 days.
35
OG00437
OG00529
OG00631
OG00733
OG00832
OG00934
0.048
± 0.033
OG0040.092± 0.032
OG0050.138± 0.036
OG0060.032± 0.035
OG0070.087± 0.034
OG0080.124± 0.034
OG0090.058± 0.033
Mean Difference (Final Values)
0.147
2-Sided
95
0.077
0.216
Superiority or Other
OG000
OG003
Mixed Models Analysis
0.006
Mean Difference (Final Values)
0.095
2-Sided
95
0.027
0.162
Superiority or Other
OG000
OG004
Mixed Models Analysis
<0.001
Mean Difference (Final Values)
0.140
2-Sided
95
0.074
0.205
Superiority or Other
OG000
OG005
Mixed Models Analysis
<0.001
Mean Difference (Final Values)
0.186
2-Sided
95
0.113
0.259
Superiority or Other
OG000
OG006
Mixed Models Analysis
0.030
Mean Difference (Final Values)
0.079
2-Sided
95
0.008
0.151
Superiority or Other
OG000
OG007
Mixed Models Analysis
<0.001
Mean Difference (Final Values)
0.134
2-Sided
95
0.064
0.204
Superiority or Other
OG000
OG008
Mixed Models Analysis
<0.001
Mean Difference (Final Values)
0.172
2-Sided
95
0.101
0.242
Superiority or Other
OG000
OG009
Mixed Models Analysis
0.003
Mean Difference (Final Values)
0.105
2-Sided
95
0.037
0.173
Superiority or Other
UMEC 62.5 µg QD
Participants received UMEC 62.5 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
OG002
UMEC 125 µg QD
Participants received UMEC 125 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
OG003
UMEC 250 µg QD
Participants received UMEC 250 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
OG004
UMEC 500 µg QD
Participants received UMEC 500 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
OG005
UMEC 1000 µg QD
Participants received UMEC 1000 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
OG006
UMEC 62.5 µg BID
Participants received UMEC 62.5 µg in the morning via DPI A and in the evening via DPI B for 14 days.
OG007
UMEC 125 µg BID
Participants received UMEC 125 µg in the morning via DPI A and in the evening via DPI B for 14 days.
OG008
UMEC 250 µg BID
Participants received UMEC 250 µg in the morning via DPI A and in the evening via DPI B for 14 days.
OG009
Tio 18 µg QD
Participants received tiotropium bromide 18 µg in the morning via the HandiHaler and placebo in the evening via DPI B for 14 days.
Units
Counts
Participants
OG000143
OG00133
OG00233
OG00334
OG00436
OG00529
OG00630
OG00732
OG00831
OG00933
Title
Denominators
Categories
Title
Measurements
OG000-0.059± 0.014
OG0010.085± 0.025
OG0020.077± 0.025
OG0030.077± 0.025
OG0040.072± 0.024
OG0050.080± 0.027
OG0060.062± 0.026
OG0070.083± 0.025
OG0080.075± 0.026
OG0090.069± 0.025
OG001
UMEC 62.5 µg QD
Participants received UMEC 62.5 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
OG002
UMEC 125 µg QD
Participants received UMEC 125 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
OG003
UMEC 250 µg QD
Participants received UMEC 250 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
OG004
UMEC 500 µg QD
Participants received UMEC 500 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
OG005
UMEC 1000 µg QD
Participants received UMEC 1000 µg in the morning via DPI A and placebo in the evening via DPI B for 14 days.
OG006
UMEC 62.5 µg BID
Participants received UMEC 62.5 µg in the morning via DPI A and in the evening via DPI B for 14 days.
OG007
UMEC 125 µg BID
Participants received UMEC 125 µg in the morning via DPI A and in the evening via DPI B for 14 days.
OG008
UMEC 250 µg BID
Participants received UMEC 250 µg in the morning via DPI A and in the evening via DPI B for 14 days.
OG009
Tio 18 µg QD
Participants received tiotropium bromide 18 µg in the morning via the HandiHaler and placebo in the evening via DPI B for 14 days.