Trial Outcomes & Findings for Efficacy and Safety of the Addition of Fluticanse Propionate/Salmeterol (250/50mcg) Twice-daily to 2 Doses of Umeclidinium Bromide (62.5 or 125mcg) Once-daily Over 12 Weeks (NCT NCT01772134)

Last Updated: 2018-01-29

Results Overview

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 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Treatment Day 84 (i.e., at Week 12). Baseline trough FEV1 is the mean of the two assessments made at -30 and -5 minutes (min) pre-dose on Treatment Day 1. Change from Baseline was calculated as the Day 85 value minus the Baseline value. Analysis was performed using a repeated measures model with covariates of treatment, Baseline (mean of the two assessments made at -30 and -5 min pre-dose on Treatment Day 1), smoking status, day, day by Baseline and day by treatment interactions.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

617 participants

Primary outcome timeframe

Baseline and Day 85

Results posted on

2018-01-29

Participant Flow

A total of 682 participants who met the eligibility criteria at Screening (Visit 1) started a 28-day Run-in Period, in which they received open-label fluticasone propionate and salmeterol (FSC) 250/50 micrograms (µg), prior to being randomized to a 12-week randomized Treatment Period.

A total of 617 participants were randomized; however, only 614 of the 617 randomized participants received at least one dose of randomized study medication in the Treatment Period.

Participant milestones

Participant milestones
Measure	Placebo QD + FSC 250/50 µg BID Participants received placebo once daily (QD) each morning via a dry powder inhaler (DPI) and fluticasone propionate and salmeterol (FSC) 250/50 micrograms (µg) twice daily (BID) (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	UMEC 62.5 µg QD + FSC 250/50 µg BID Participants received umeclidinium bromide (UMEC) 62.5 µg QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	UMEC 125 µg QD + FSC 250/50 µg BID Participants received UMEC 125 µg QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.
Overall Study STARTED	207	204	206
Overall Study Received Randomized Study Medication	205	204	205
Overall Study COMPLETED	178	190	184
Overall Study NOT COMPLETED	29	14	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo QD + FSC 250/50 µg BID Participants received placebo once daily (QD) each morning via a dry powder inhaler (DPI) and fluticasone propionate and salmeterol (FSC) 250/50 micrograms (µg) twice daily (BID) (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	UMEC 62.5 µg QD + FSC 250/50 µg BID Participants received umeclidinium bromide (UMEC) 62.5 µg QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	UMEC 125 µg QD + FSC 250/50 µg BID Participants received UMEC 125 µg QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.
Overall Study Adverse Event	6	5	10
Overall Study Withdrew Consent	3	1	5
Overall Study Lost to Follow-up	2	0	0
Overall Study Protocol Deviation	4	3	3
Overall Study Lack of Efficacy	11	5	3
Overall Study Protocol-defined Stopping Criteria	1	0	0
Overall Study Randomized Study Medication Not Received	2	0	1

Baseline Characteristics

Efficacy and Safety of the Addition of Fluticanse Propionate/Salmeterol (250/50mcg) Twice-daily to 2 Doses of Umeclidinium Bromide (62.5 or 125mcg) Once-daily Over 12 Weeks

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo QD + FSC 250/50 µg BID n=205 Participants Participants received placebo QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	UMEC 62.5 µg QD + FSC 250/50 µg BID n=204 Participants Participants received UMEC 62.5 µg QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	UMEC 125 µg QD + FSC 250/50 µg BID n=205 Participants Participants received UMEC 125 µg QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	Total n=614 Participants Total of all reporting groups
Age, Continuous	63.4 Years STANDARD_DEVIATION 8.27 • n=93 Participants	62.7 Years STANDARD_DEVIATION 7.84 • n=4 Participants	63.2 Years STANDARD_DEVIATION 8.95 • n=27 Participants	63.1 Years STANDARD_DEVIATION 8.36 • n=483 Participants
Sex: Female, Male Female	73 Participants n=93 Participants	71 Participants n=4 Participants	63 Participants n=27 Participants	207 Participants n=483 Participants
Sex: Female, Male Male	132 Participants n=93 Participants	133 Participants n=4 Participants	142 Participants n=27 Participants	407 Participants n=483 Participants
Race/Ethnicity, Customized African American/African Heritage	4 Participants n=93 Participants	5 Participants n=4 Participants	3 Participants n=27 Participants	12 Participants n=483 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants
Race/Ethnicity, Customized Japanese/East Asian Heritage/ South East Asian	20 Participants n=93 Participants	24 Participants n=4 Participants	19 Participants n=27 Participants	63 Participants n=483 Participants
Race/Ethnicity, Customized White	181 Participants n=93 Participants	175 Participants n=4 Participants	182 Participants n=27 Participants	538 Participants n=483 Participants

PRIMARY outcome

Timeframe: Baseline and Day 85

Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of randomized study medication in the Treatment Period. Only those participants available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Placebo QD + FSC 250/50 µg BID n=177 Participants Participants received placebo QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	UMEC 62.5 µg QD + FSC 250/50 µg BID n=190 Participants Participants received UMEC 62.5 µg QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	UMEC 125 µg QD + FSC 250/50 µg BID n=184 Participants Participants received UMEC 125 µg QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.
Change From Baseline in the Trough Forced Expiratory Volume in One Second (FEV1) on Day 85	-0.022 Liters Standard Error 0.0146	0.125 Liters Standard Error 0.0142	0.116 Liters Standard Error 0.0144

SECONDARY outcome

Timeframe: Baseline and Day 84

Population: ITT Population. Only those participants available at the indicated time point were analyzed.

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 curve, and then dividing the value by the relevant time interval. The weighted mean was calculated using the 24-hour serial FEV1 measurements at Day 84, which included pre-dose, and post-dose at 15 min, 30 min, 1 hour, 3 hours, and 6 hours. Baseline trough FEV1 is the mean of the two assessments made at -30 and -5 min pre-dose on Treatment Day 1. Change from Baseline was calculated as the Day 84 value minus the Baseline value. Analysis was performed using a repeated measures model with covariates of treatment, Baseline (mean of the two assessments made at -30and -5 min pre-dose on Treatment Day 1), smoking status, day, day by Baseline and day by treatment interactions.

Outcome measures

Outcome measures
Measure	Placebo QD + FSC 250/50 µg BID n=176 Participants Participants received placebo QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	UMEC 62.5 µg QD + FSC 250/50 µg BID n=186 Participants Participants received UMEC 62.5 µg QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	UMEC 125 µg QD + FSC 250/50 µg BID n=183 Participants Participants received UMEC 125 µg QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.
Change From Baseline in Weighted Mean 0-6 Hour FEV1 Obtained Post-dose at Day 84	0.032 Liters Standard Error 0.0140	0.196 Liters Standard Error 0.0138	0.192 Liters Standard Error 0.0138

SECONDARY outcome

Timeframe: Baseline and Weeks 1-12

Population: ITT Population. Only those participants available at the indicated time point were analyzed.

A rescue-free day is defined as a day on which no rescue medication was taken. Baseline calculations include a period of the later of 27 days before Visit 2 and the day after Visit 1, up to and including Day 1. The Weeks 1-12 calculations include a period from Study Day 2 up to the earlier of Study Day 85 and the day before Visit 7. Change from Baseline was calculated as the Weeks 1-12 value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Placebo QD + FSC 250/50 µg BID n=184 Participants Participants received placebo QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	UMEC 62.5 µg QD + FSC 250/50 µg BID n=191 Participants Participants received UMEC 62.5 µg QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	UMEC 125 µg QD + FSC 250/50 µg BID n=183 Participants Participants received UMEC 125 µg QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.
Change From Baseline in the Mean Percentage of Rescue-free Days Over Weeks 1-12	4.9 Percentage of days Standard Deviation 25.66	13.3 Percentage of days Standard Deviation 28.66	11.1 Percentage of days Standard Deviation 25.70

SECONDARY outcome

Timeframe: Baseline and Weeks 1-12

Population: ITT Population. Only those participants available at the indicated time point were analyzed.

The mean number of puffs per day of rescue albuterol/salbutamol at Baseline and on-treatment was recorded. The total puffs of rescue albuterol/salbutamol for each day was calculated as: (number of puffs + \[2 \* number of nebules\]). Baseline calculations include a period of the later of 27 days before Visit 2 and the day after Visit 1, up to and including Day 1. The Weeks 1-12 calculations include a period from Study Day 2 up to the earlier of Study Day 85 and the day before Visit 7. Change from Baseline was calculated as the Weeks 1-12 value value minus the Baseline value. Analysis was performed using an analysis of covariance (ANCOVA) model with covariates of treatment, Baseline (mean during the 4 weeks prior to Day 1), and smoking status.

Outcome measures

Outcome measures
Measure	Placebo QD + FSC 250/50 µg BID n=184 Participants Participants received placebo QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	UMEC 62.5 µg QD + FSC 250/50 µg BID n=191 Participants Participants received UMEC 62.5 µg QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	UMEC 125 µg QD + FSC 250/50 µg BID n=183 Participants Participants received UMEC 125 µg QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.
Change From Baseline in the Mean Number of Puffs Per Day of Rescue Albuterol/Salbutamol Over Weeks 1-12	-0.2 puffs Standard Error 0.09	-0.5 puffs Standard Error 0.09	-0.5 puffs Standard Error 0.09

Adverse Events

Placebo QD + FSC 250/50 µg BID

Serious events: 8 serious events

Other events: 21 other events

Deaths: 0 deaths

UMEC 62.5 µg QD + FSC 250/50 µg BID

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

UMEC 125 µg QD + FSC 250/50 µg BID

Serious events: 6 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo QD + FSC 250/50 µg BID n=205 participants at risk Participants received placebo QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	UMEC 62.5 µg QD + FSC 250/50 µg BID n=204 participants at risk Participants received UMEC 62.5 µg QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.	UMEC 125 µg QD + FSC 250/50 µg BID n=205 participants at risk Participants received UMEC 125 µg QD each morning via a DPI and FSC 250/50 µg BID (one inhalation each morning and one inhalation each evening) via a DPI for 12 weeks.
Nervous system disorders Headache	4.9% 10/205 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) are defined as those events occurring while participants were on treatment or those events with an onset during the follow-up period (up to 13 weeks). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the Treatment Period.	4.4% 9/204 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) are defined as those events occurring while participants were on treatment or those events with an onset during the follow-up period (up to 13 weeks). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the Treatment Period.	6.3% 13/205 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) are defined as those events occurring while participants were on treatment or those events with an onset during the follow-up period (up to 13 weeks). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the Treatment Period.
Infections and infestations Nasopharyngitis	4.9% 10/205 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) are defined as those events occurring while participants were on treatment or those events with an onset during the follow-up period (up to 13 weeks). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the Treatment Period.	2.5% 5/204 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) are defined as those events occurring while participants were on treatment or those events with an onset during the follow-up period (up to 13 weeks). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the Treatment Period.	2.4% 5/205 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) are defined as those events occurring while participants were on treatment or those events with an onset during the follow-up period (up to 13 weeks). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the Treatment Period.
Respiratory, thoracic and mediastinal disorders Cough	1.5% 3/205 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) are defined as those events occurring while participants were on treatment or those events with an onset during the follow-up period (up to 13 weeks). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the Treatment Period.	3.4% 7/204 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) are defined as those events occurring while participants were on treatment or those events with an onset during the follow-up period (up to 13 weeks). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the Treatment Period.	2.4% 5/205 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) are defined as those events occurring while participants were on treatment or those events with an onset during the follow-up period (up to 13 weeks). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the Treatment Period.

Additional Information

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Phone: 866-435-7343

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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.
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