Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Combination of GSK573719 and GW642444 in Subjects With COPD (NCT NCT01039675)
NCT ID: NCT01039675
Last Updated: 2017-11-08
Results Overview
Pulse rate is defined as the number of heartbeats in a minute. The weighted mean pulse rate was derived by calculating the area under the pulse rate/time curve (AUC), and then dividing the value by the time interval over which the AUC was calculated. The weighted mean pulse rate was calculated using the 0 to 6 hours post dose measurements at Day 28, which included pre-dose, and post-dose 15 minutes, 45 minutes, 1.5 hours, 3 hours and 6 hours. Baseline pulse rate is the most recent result taken on or before pre-dose Day 1. Change from Baseline is the weighted mean pulse rate at Day 28 minus the Baseline value. Analysis was performed using a repeated measures model with covariates of Baseline pulse rate, sex, age, smoking status, treatment and day and day by treatment and day by Baseline interactions.
COMPLETED
PHASE2
51 participants
Baseline and Day 28
2017-11-08
Participant Flow
Participants (par.) who met eligibility criteria at Screening (Visit 1) completed a 5- to 8-day Run-in period and were then randomized to a 4-week treatment period. A total of 77 par. were screened; 52 par. were randomized and 51 par. received at least one dose of study drug (one par. was randomized in error but did not receive study drug).
Participant milestones
| Measure |
Placebo
Participants received matching placebo once daily (QD) via a dry powder inhaler (DPI) in the morning for 4 weeks.
|
UMEC/VI 500/25 µg QD
Participants received umeclidinium bromide/vilanterol (UMEC/VI) 500/25 micrograms (µg) QD via a DPI in the morning for 4 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
9
|
42
|
|
Overall Study
COMPLETED
|
9
|
35
|
|
Overall Study
NOT COMPLETED
|
0
|
7
|
Reasons for withdrawal
| Measure |
Placebo
Participants received matching placebo once daily (QD) via a dry powder inhaler (DPI) in the morning for 4 weeks.
|
UMEC/VI 500/25 µg QD
Participants received umeclidinium bromide/vilanterol (UMEC/VI) 500/25 micrograms (µg) QD via a DPI in the morning for 4 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
2
|
|
Overall Study
Lack of Efficacy
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Physician Decision
|
0
|
1
|
Baseline Characteristics
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Combination of GSK573719 and GW642444 in Subjects With COPD
Baseline characteristics by cohort
| Measure |
Placebo
n=9 Participants
Participants received matching placebo QD via a DPI in the morning for 4 weeks.
|
UMEC/VI 500/25 µg QD
n=42 Participants
Participants received UMEC/VI 500/25 µg QD via a DPI in the morning for 4 weeks.
|
Total
n=51 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58.7 Years
STANDARD_DEVIATION 9.77 • n=5 Participants
|
59.2 Years
STANDARD_DEVIATION 9.48 • n=7 Participants
|
59.1 Years
STANDARD_DEVIATION 9.43 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
1 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
8 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Day 28Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment who received \>= 1 dose of randomized study medication. All participants with \>=1 post-BL assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 28.
Pulse rate is defined as the number of heartbeats in a minute. The weighted mean pulse rate was derived by calculating the area under the pulse rate/time curve (AUC), and then dividing the value by the time interval over which the AUC was calculated. The weighted mean pulse rate was calculated using the 0 to 6 hours post dose measurements at Day 28, which included pre-dose, and post-dose 15 minutes, 45 minutes, 1.5 hours, 3 hours and 6 hours. Baseline pulse rate is the most recent result taken on or before pre-dose Day 1. Change from Baseline is the weighted mean pulse rate at Day 28 minus the Baseline value. Analysis was performed using a repeated measures model with covariates of Baseline pulse rate, sex, age, smoking status, treatment and day and day by treatment and day by Baseline interactions.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received matching placebo QD via a DPI in the morning for 4 weeks.
|
UMEC/VI 500/25 µg QD
n=35 Participants
Participants received UMEC/VI 500/25 µg QD via a DPI in the morning for 4 weeks.
|
|---|---|---|
|
Change From Baseline in Weighted Mean Pulse Rate Over 0 to 6 Hours Post-dose at Day 28
|
1.4 Beats per minutes (bpm)
Standard Error 2.20
|
0.9 Beats per minutes (bpm)
Standard Error 1.05
|
SECONDARY outcome
Timeframe: Baseline, Day 1, and Day 14Population: ITT Population. All participants with \>=1 post-BL assessment are included in the analysis. Different participants may have been analyzed at different time points (represented by n=X, X in the category titles), so the overall number of participants analyzed reflects everyone in the ITT Population with data avaialable at \>=1 time point.
Pulse rate is defined as the number of heartbeats in a minute. The weighted mean pulse rate was derived by calculating the area under the pulse rate/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 pulse rate was calculated using the 0 to 6 hours post dose measurements on Day 1 and Day 14, which included pre-dose, and post-dose 15 minutes, 45 minutes, 1.5 hours, 3 hours and 6 hours. Baseline pulse rate is the most recent result taken on or before pre-dose Day 1. Change from Baseline is the weighted mean pulse rate at Day 1 or Day 14 minus the Baseline value. Analysis was performed using a repeated measures model with covariates of Baseline pulse rate, sex, age, smoking status, treatment and day and day by treatment and day by Baseline interactions.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received matching placebo QD via a DPI in the morning for 4 weeks.
|
UMEC/VI 500/25 µg QD
n=42 Participants
Participants received UMEC/VI 500/25 µg QD via a DPI in the morning for 4 weeks.
|
|---|---|---|
|
Change From Baseline in Weighted Mean Pulse Rate Over 0 to 6 Hours Post-dose at Day 1 and Day 14
Day 1, n=9, 42
|
-1.2 Beats per minutes
Standard Error 2.04
|
-0.6 Beats per minutes
Standard Error 0.92
|
|
Change From Baseline in Weighted Mean Pulse Rate Over 0 to 6 Hours Post-dose at Day 1 and Day 14
Day 14, n=9, 39
|
-1.7 Beats per minutes
Standard Error 2.70
|
3.1 Beats per minutes
Standard Error 1.26
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Day 14 and Day 28Population: ITT Population. The overall number of participants presented is the number who provided at least one post-Baseline assessment of 0-6 hours maximum or minimum pulse rate. Those participants who provided data at the indicated time point are represented by n=X, X in the category titles.
Pulse rate is defined as the number of heartbeats in a minute (m). A maximum post-Baseline pulse rate was derived as the maximum value recorded at Days 1, 14 and 28. A minimum post-Baseline pulse rate was derived as the minimum value recorded at Days 1, 14 and 28. The maximum and minimum pulse rates were calculated using the 0 to 6 hours (h) post dose measurements on Days 1, 14 and 28, which included pre-dose, and post-dose 15 m, 45 m, 1.5 h, 3 h and 6 h. Maximum and minimum post-Baseline rate were calculated using the nominal 0-6 h post-dose records, and only records collected during the actual 0-7 h post-dose interval were used. Baseline pulse rate is the most recent result taken on or before pre-dose Day 1. Change from Baseline is the maximum or minimum pulse rate minus the Baseline value. Analysis performed using a repeated measures model with covariates of Baseline pulse rate, sex, age, smoking status, treatment and day and day by treatment and day by Baseline interactions.
Outcome measures
| Measure |
Placebo
n=9 Participants
Participants received matching placebo QD via a DPI in the morning for 4 weeks.
|
UMEC/VI 500/25 µg QD
n=42 Participants
Participants received UMEC/VI 500/25 µg QD via a DPI in the morning for 4 weeks.
|
|---|---|---|
|
Change From Baseline in Maximum and Minimum Pulse Rate 0 to 6 Hours Post-dose on Days 1, 14, and 28
Maximum pulse rate, Day 1, n=9, 42
|
4.5 Beats per minutes
Standard Error 2.53
|
6.4 Beats per minutes
Standard Error 1.15
|
|
Change From Baseline in Maximum and Minimum Pulse Rate 0 to 6 Hours Post-dose on Days 1, 14, and 28
Maximum pulse rate, Day 14, n=9, 40
|
4.9 Beats per minutes
Standard Error 2.93
|
9.7 Beats per minutes
Standard Error 1.37
|
|
Change From Baseline in Maximum and Minimum Pulse Rate 0 to 6 Hours Post-dose on Days 1, 14, and 28
Maximum pulse rate, Day 28, n=9, 35
|
7.4 Beats per minutes
Standard Error 2.45
|
6.1 Beats per minutes
Standard Error 1.19
|
|
Change From Baseline in Maximum and Minimum Pulse Rate 0 to 6 Hours Post-dose on Days 1, 14, and 28
Minimum pulse rate, Day 1, n=9, 42
|
-7.0 Beats per minutes
Standard Error 2.10
|
-6.7 Beats per minutes
Standard Error 0.95
|
|
Change From Baseline in Maximum and Minimum Pulse Rate 0 to 6 Hours Post-dose on Days 1, 14, and 28
Minimum pulse rate, Day 14, n=9, 40
|
-7.2 Beats per minutes
Standard Error 2.78
|
-3.2 Beats per minutes
Standard Error 1.28
|
|
Change From Baseline in Maximum and Minimum Pulse Rate 0 to 6 Hours Post-dose on Days 1, 14, and 28
Minimum pulse rate, Day 28, n=9, 35
|
-6.8 Beats per minutes
Standard Error 2.37
|
-5.1 Beats per minutes
Standard Error 1.15
|
Adverse Events
Placebo
UMEC/VI 500/25 µg QD
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=9 participants at risk
Participants received matching placebo QD via a DPI in the morning for 4 weeks.
|
UMEC/VI 500/25 µg QD
n=42 participants at risk
Participants received UMEC/VI 500/25 µg QD via a DPI in the morning for 4 weeks.
|
|---|---|---|
|
Infections and infestations
Sinusitis
|
11.1%
1/9 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication up to 4 weeks.
On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants who were randomized to treatment and who had received at least one dose of study medication.
|
2.4%
1/42 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication up to 4 weeks.
On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants who were randomized to treatment and who had received at least one dose of study medication.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER