Trial Outcomes & Findings for Efficacy and Safety of the Addition of Fluticasone Propionate/Salmeterol (250/50mcg) Twice-daily to 2 Doses of Umeclidinium Bromide Inhalation Powder (62.5 or 125mcg) Once-daily Over 12 Weeks. (NCT NCT01772147)

Last Updated: 2017-03-23

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

608 participants

Primary outcome timeframe

Baseline and Day 85

Results posted on

2017-03-23

Participant Flow

A total of 872 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 608 participants were randomized in the study; however, only 606 of these 608 participants were included in the Intent-to-Treat Population, comprised of all participants randomized to treatment who 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 FSC 250/50 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	201	203	202
Overall Study COMPLETED	170	178	184
Overall Study NOT COMPLETED	31	25	18

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 FSC 250/50 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	13	10	6
Overall Study Withdrew Consent	7	8	4
Overall Study Lost to Follow-up	1	0	1
Overall Study Protocol Deviation	2	1	1
Overall Study Lack of Efficacy	8	6	6

Baseline Characteristics

Efficacy and Safety of the Addition of Fluticasone Propionate/Salmeterol (250/50mcg) Twice-daily to 2 Doses of Umeclidinium Bromide Inhalation Powder (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=201 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=203 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=202 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=606 Participants Total of all reporting groups
Age, Continuous	65.7 Years STANDARD_DEVIATION 7.92 • n=5 Participants	64.5 Years STANDARD_DEVIATION 8.31 • n=7 Participants	65.5 Years STANDARD_DEVIATION 7.89 • n=5 Participants	65.2 Years STANDARD_DEVIATION 8.04 • n=4 Participants
Sex: Female, Male Female	78 Participants n=5 Participants	63 Participants n=7 Participants	82 Participants n=5 Participants	223 Participants n=4 Participants
Sex: Female, Male Male	123 Participants n=5 Participants	140 Participants n=7 Participants	120 Participants n=5 Participants	383 Participants n=4 Participants
Race/Ethnicity, Customized African American/African Heritage	3 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Japanese/East Asian Heritage/South East Asian	37 Participants n=5 Participants	33 Participants n=7 Participants	27 Participants n=5 Participants	97 Participants n=4 Participants
Race/Ethnicity, Customized White	161 Participants n=5 Participants	164 Participants n=7 Participants	171 Participants n=5 Participants	496 Participants n=4 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=169 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=178 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 Trough Forced Expiratory Volume in One Second (FEV1) on Day 85	-0.001 Liters Standard Error 0.0136	0.126 Liters Standard Error 0.0133	0.147 Liters Standard Error 0.0132

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 6-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=171 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=178 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 Weighted Mean 0-6 Hour FEV1 Obtained Post-dose at Day 84	0.052 Liters Standard Error 0.0137	0.196 Liters Standard Error 0.0135	0.217 Liters Standard Error 0.0133

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=174 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=187 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	1.9 Percentage of days Standard Deviation 27.38	8.4 Percentage of days Standard Deviation 30.23	15.2 Percentage of days Standard Deviation 28.25

SECONDARY outcome

Timeframe: Baseline and Weeks1- 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 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=174 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=187 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 0.10	-0.4 puffs Standard Error 0.10	-0.7 puffs Standard Error 0.10

Adverse Events

Placebo QD + FSC 250/50 µg BID

Serious events: 15 serious events

Other events: 18 other events

Deaths: 0 deaths

UMEC 62.5 µg QD + FSC 250/50 µg BID

Serious events: 6 serious events

Other events: 13 other events

Deaths: 0 deaths

UMEC 125 µg QD + FSC 250/50 µg BID

Serious events: 6 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo QD + FSC 250/50 µg BID n=201 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=203 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=202 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.
Infections and infestations Nasopharyngitis	4.5% 9/201 • 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.	3.0% 6/203 • 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.	5.0% 10/202 • 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.
Nervous system disorders Headache	4.5% 9/201 • 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% 9/203 • 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.	3.0% 6/202 • 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

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER