Trial Outcomes & Findings for Study Evaluating the Efficacy and Safety of Fluticasone Furoate/Vilanterol Inhalation Powder (FF/VI) Compared With Vilanterol Inhalation Powder (VI) in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT02105974)

Last Updated: 2018-01-24

Results Overview

Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 14, 28, 56 and 84. BL was defined as the mean of the assessments made 30 minutes pre-dose and immediately pre-dose on Treatment Day 1.Trough FEV1 was defined as the mean of the FEV1 values obtained 23 and 24 hours after previous morning's dosing. Change from BL was calculated as the average at each visit minus the BL value. Analysis was performed using a repeated measures model with covariates of treatment, reversibility status (stratum), BL, region, day, day by BL and day by treatment interactions.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1621 participants

Primary outcome timeframe

Baseline to Day 84

Results posted on

2018-01-24

Participant Flow

Par meeting continuation criteria during the run-in period were randomized (1:1) to receive fluticasone furoate (FF)/vilanterol (VI) or VI. Of the 2423 par screened, 1622 were randomized. 1620 received at least one dose of double-blind study medication and comprised the Intent-to-Treat population.

Participants(par) with a history of chronic obstructive pulmonary disease(COPD) meeting eligibility criteria at screening were enrolled in a 2-week, single-blind(placebo) run-in period to obtain baseline use of albuterol(salbutamol), COPD symptom scores and disease stability.

Participant milestones

Participant milestones
Measure	Placebo Run-In Participants received placebo once daily (QD) in the morning for 2 weeks. In addition, participants were provided an inhaled short-acting beta2-receptor agonist (SABA), albuterol (salbutamol) (metered dose inhaler \[MDI\] or nebules), to be used as a rescue medication for relief of chronic obstructive pulmonary disease (COPD) symptoms during the Run-in and Treatment Periods.	FF/VI 100/25 µg QD Participants received fluticasone furoate/vilaterol (FF/VI) 100/25 microgram(µg) inhalation via a dry powder inhaler (DPI) once daily (QD) in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler \[MDI\] or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.	VI 25 µg QD Participants received VI 25 µg inhalation QD via a DPI in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler \[MDI\] or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.
2 Week Run-in Period STARTED	2423	0	0
2 Week Run-in Period COMPLETED	1622	0	0
2 Week Run-in Period NOT COMPLETED	801	0	0
12 Week (Wk) Treatment Period (TP) STARTED	0	806	814
12 Week (Wk) Treatment Period (TP) Completed the Treatment(Trt) Period	0	764	754
12 Week (Wk) Treatment Period (TP) COMPLETED	0	764	756
12 Week (Wk) Treatment Period (TP) NOT COMPLETED	0	42	58

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Run-In Participants received placebo once daily (QD) in the morning for 2 weeks. In addition, participants were provided an inhaled short-acting beta2-receptor agonist (SABA), albuterol (salbutamol) (metered dose inhaler \[MDI\] or nebules), to be used as a rescue medication for relief of chronic obstructive pulmonary disease (COPD) symptoms during the Run-in and Treatment Periods.	FF/VI 100/25 µg QD Participants received fluticasone furoate/vilaterol (FF/VI) 100/25 microgram(µg) inhalation via a dry powder inhaler (DPI) once daily (QD) in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler \[MDI\] or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.	VI 25 µg QD Participants received VI 25 µg inhalation QD via a DPI in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler \[MDI\] or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.
2 Week Run-in Period Withdrew during pre-screen period	158	0	0
2 Week Run-in Period Did not meet inclusion/exclusion criteri	603	0	0
2 Week Run-in Period Adverse Event	6	0	0
2 Week Run-in Period Study closed/terminated	1	0	0
2 Week Run-in Period Lost to Follow-up	2	0	0
2 Week Run-in Period Withdrew consent	23	0	0
2 Week Run-in Period Investigator discretion	8	0	0
12 Week (Wk) Treatment Period (TP) Adverse Event	0	14	18
12 Week (Wk) Treatment Period (TP) Lack of Efficacy	0	6	9
12 Week (Wk) Treatment Period (TP) Protocol deviation	0	2	6
12 Week (Wk) Treatment Period (TP) Participant reached stopping criteria	0	1	2
12 Week (Wk) Treatment Period (TP) Lost to Follow-up	0	0	1
12 Week (Wk) Treatment Period (TP) Physician Decision	0	7	4
12 Week (Wk) Treatment Period (TP) Withdrawal by Subject	0	12	18

Baseline Characteristics

Study Evaluating the Efficacy and Safety of Fluticasone Furoate/Vilanterol Inhalation Powder (FF/VI) Compared With Vilanterol Inhalation Powder (VI) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FF/VI 100/25 µg QD n=806 Participants Participants received fluticasone furoate/vilaterol (FF/VI) 100/25 microgram(µg) inhalation via a dry powder inhaler (DPI) once daily (QD) in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.	VI 25 µg QD n=814 Participants Participants received VI 25 µg inhalation QD via a DPI in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.	Total n=1620 Participants Total of all reporting groups
Age, Continuous	65.3 Years STANDARD_DEVIATION 8.58 • n=5 Participants	65.4 Years STANDARD_DEVIATION 9.02 • n=7 Participants	65.3 Years STANDARD_DEVIATION 8.80 • n=5 Participants
Sex: Female, Male Female	201 Participants n=5 Participants	189 Participants n=7 Participants	390 Participants n=5 Participants
Sex: Female, Male Male	605 Participants n=5 Participants	625 Participants n=7 Participants	1230 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	6 Participants n=5 Participants	10 Participants n=7 Participants	16 Participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	77 Participants n=5 Participants	77 Participants n=7 Participants	154 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	185 Participants n=5 Participants	185 Participants n=7 Participants	370 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	538 Participants n=5 Participants	541 Participants n=7 Participants	1079 Participants n=5 Participants
Race/Ethnicity, Customized Mixed Race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Day 84

Population: Intent-to-Treat (ITT) Population: all randomized par. who received at least one dose of study medication. Number of par. presented represent those with data available at the time point being presented; however, all par. in the ITT population without missing covariate information and with at least one post BL measurement are included in the analysis

Outcome measures

Outcome measures
Measure	FF/VI 100/25 µg QD n=759 Participants Participants received fluticasone furoate/vilaterol (FF/VI) 100/25 microgram(µg) inhalation via a dry powder inhaler (DPI) once daily (QD) in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.	VI 25 µg QD n=749 Participants Participants received VI 25 µg inhalation QD via a DPI in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.
Mean Change From Baseline (BL) in Clinic Visit Trough (Pre-bronchodilator and Pre-dose) FEV1, on Treatment Day 84	0.116 Liter Standard Error 0.0074	0.082 Liter Standard Error 0.0075

SECONDARY outcome

Timeframe: BL (Week -1), Week 1 to Week 12

Population: ITT Population, all randomized participants who received at least one dose of study medication. Only those participants with at least 1 on treatment rescue medication measurement during the treatment period and without missing covariate information were analyzed.

Participants were given daily record cards for daily completion from BL (Week -1) through Week 12 (Visit 7) each morning and prior prior to taking study medication (i.e., single-blind and double-blind study medication), supplemental medication (albuterol \[salbutamol\] if received). Participants recorded number of occasions supplemental albuterol/salbutamol (MDI and/or nebules) or oxitropium bromide (applicable sites in Japan) used over the previous 24 hours and any medical problems that they had experienced and any medication used to treat these medical problems over the previous 24 hours. Rescue-free 24-hour periods are defined as the 24-hour periods in which the rescue medication (albuterol \[salbutamol\]) was not used. The percentage of 24-hour periods are summarized for the entire treatment period (12 weeks). Analysis was performed using an analysis of covariance (ANCOVA) model with covariates of treatment, reversibility status (stratum), baseline (week -1) and region.

Outcome measures

Outcome measures
Measure	FF/VI 100/25 µg QD n=801 Participants Participants received fluticasone furoate/vilaterol (FF/VI) 100/25 microgram(µg) inhalation via a dry powder inhaler (DPI) once daily (QD) in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.	VI 25 µg QD n=802 Participants Participants received VI 25 µg inhalation QD via a DPI in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.
Percentage of Rescue-free 24-hour Periods Over the Entire 12-week Treatment Period	47.03 Percentage of rescue-free periods Standard Error 1.070	44.41 Percentage of rescue-free periods Standard Error 1.069

SECONDARY outcome

Timeframe: From the start of double blind study medication until visit 7 (week 12)/Early withdrawal

Population: ITT Population

Time to first on-treatment exacerbation was analysed using a Cox proportional hazards model with terms for treatment, reversibility status and percent predicted FEV1 at screening. Exacerbation of COPD is defined by a worsening of symptoms requiring additional treatment. Moderate COPD exacerbation is worsening symptoms of COPD that require treatment with antibiotics and/or systemic corticosteroids. Severe COPD exacerbation is worsening symptoms of COPD that require treatment with in-patient hospitalization. The number of participants with On-Treatment moderate or severe COPD exacerbations are presented.

Outcome measures

Outcome measures
Measure	FF/VI 100/25 µg QD n=806 Participants Participants received fluticasone furoate/vilaterol (FF/VI) 100/25 microgram(µg) inhalation via a dry powder inhaler (DPI) once daily (QD) in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.	VI 25 µg QD n=814 Participants Participants received VI 25 µg inhalation QD via a DPI in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.
Time to First On-treatment Occurrence of Moderate or Severe COPD Exacerbation	69 Participants	114 Participants

Adverse Events

FF/VI 100/25 µg QD

Serious events: 27 serious events

Other events: 72 other events

Deaths: 0 deaths

VI 25 µg QD

Serious events: 35 serious events

Other events: 64 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	FF/VI 100/25 µg QD n=806 participants at risk Participants received fluticasone furoate/vilaterol (FF/VI) 100/25 microgram(µg) inhalation via a dry powder inhaler (DPI) once daily (QD) in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.	VI 25 µg QD n=814 participants at risk Participants received VI 25 µg inhalation QD via a DPI in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.
Infections and infestations Nasopharyngitis	6.1% 49/806 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of double-blind (DB) study treatment (Visit 2) through the follow up contact (up to 13 weeks). On-treatment AE or SAE is defined as an AE with an onset date on or after the start date of DB study medication, but not later than one day after the last dose of DB study medication. AEs are reported for participants of the ITT, comprised of all randomized participants who received at least one dose of study medication during the treatment period	5.9% 48/814 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of double-blind (DB) study treatment (Visit 2) through the follow up contact (up to 13 weeks). On-treatment AE or SAE is defined as an AE with an onset date on or after the start date of DB study medication, but not later than one day after the last dose of DB study medication. AEs are reported for participants of the ITT, comprised of all randomized participants who received at least one dose of study medication during the treatment period
Nervous system disorders Headache	3.6% 29/806 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of double-blind (DB) study treatment (Visit 2) through the follow up contact (up to 13 weeks). On-treatment AE or SAE is defined as an AE with an onset date on or after the start date of DB study medication, but not later than one day after the last dose of DB study medication. AEs are reported for participants of the ITT, comprised of all randomized participants who received at least one dose of study medication during the treatment period	2.3% 19/814 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of double-blind (DB) study treatment (Visit 2) through the follow up contact (up to 13 weeks). On-treatment AE or SAE is defined as an AE with an onset date on or after the start date of DB study medication, but not later than one day after the last dose of DB study medication. AEs are reported for participants of the ITT, comprised of all randomized participants who received at least one dose of study medication during the treatment period

Additional Information

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