Trial Outcomes & Findings for Evaluating the Efficacy and Safety of Fluticasone Furoate/Vilanterol Trifenatate in the Treatment of Asthma in Adolescent and Adult Subjects of Asian Ancestry. (NCT NCT01498679)

Results Overview

Peak Expiratory Flow is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline was calculated as the value of the averaged daily PM PEF over the 12-week Treatment Period minus the Baseline value. Analysis was performed using Analysis of Covariance (ANCOVA) with covariates of Baseline, region, sex, age, and treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

311 participants

Primary outcome timeframe

Baseline and Weeks 1-12 (up to Day 84)

Results posted on

2017-03-08

Participant Flow

A total of 311 participants were randomized to treatment. However, 4 participants were randomized in error and did not receive any study treatment. These participants were not included in the Intent-to-Treat (ITT) Population, which was comprised of all participants randomized to treatment who received \>=1 dose of trial medication.

At screening, participants who met all of the inclusion criteria entered a 2-week Run-in Period. Participants continued on inhaled corticosteroid (ICS) therapy throughout the Run-in Period. At the end of the Run-in Period, participants meeting the randomization criteria entered a 12-week Treatment Period and received one of the two treatments.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo once daily (OD) in the evening,via a Dry Powder Inhaler (DPI), for a period of 12 weeks.	Fluticasone Furoate/Vilanterol 100/25 µg Once Daily Participants received fluticasone furoate (FF)/vilanterol (VI) 100/25 micrograms (µg) OD in the evening,via a DPI, for a period of 12 weeks.
Overall Study STARTED	154	153
Overall Study COMPLETED	65	131
Overall Study NOT COMPLETED	89	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo once daily (OD) in the evening,via a Dry Powder Inhaler (DPI), for a period of 12 weeks.	Fluticasone Furoate/Vilanterol 100/25 µg Once Daily Participants received fluticasone furoate (FF)/vilanterol (VI) 100/25 micrograms (µg) OD in the evening,via a DPI, for a period of 12 weeks.
Overall Study Adverse Event	1	4
Overall Study Lack of Efficacy	72	12
Overall Study Protocol Violation	4	0
Overall Study Physician Decision	0	2
Overall Study Withdrawal by Subject	12	4

Baseline Characteristics

Evaluating the Efficacy and Safety of Fluticasone Furoate/Vilanterol Trifenatate in the Treatment of Asthma in Adolescent and Adult Subjects of Asian Ancestry.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=154 Participants Participants received placebo OD in the evening,via a DPI, for a period of 12 weeks.	Fluticasone Furoate/Vilanterol 100/25 µg Once Daily n=153 Participants Participants received FF/VI 100/25 µg OD in the evening,via a DPI, for a period of 12 weeks.	Total n=307 Participants Total of all reporting groups
Age, Continuous	47.4 Years STANDARD_DEVIATION 13.90 • n=5 Participants	47.0 Years STANDARD_DEVIATION 14.01 • n=7 Participants	47.2 Years STANDARD_DEVIATION 13.94 • n=5 Participants
Sex: Female, Male Female	88 Participants n=5 Participants	83 Participants n=7 Participants	171 Participants n=5 Participants
Sex: Female, Male Male	66 Participants n=5 Participants	70 Participants n=7 Participants	136 Participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	132 Participants n=5 Participants	125 Participants n=7 Participants	257 Participants n=5 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	22 Participants n=5 Participants	28 Participants n=7 Participants	50 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Weeks 1-12 (up to Day 84)

Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment who received \>=1 dose of trial medication. The primary endpoint analysis only included participants who had PM PEF data for \>=4 days in the BL week prior to randomization and \>=4 days after randomization. Only participants available at the indicated time point were assessed.

Peak Expiratory Flow is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline was calculated as the value of the averaged daily PM PEF over the 12-week Treatment Period minus the Baseline value. Analysis was performed using Analysis of Covariance (ANCOVA) with covariates of Baseline, region, sex, age, and treatment.

Outcome measures

Outcome measures
Measure	Placebo n=151 Participants Participants received placebo OD in the evening,via a DPI, for a period of 12 weeks.	Fluticasone Furoate/Vilanterol 100/25 µg Once Daily n=153 Participants Participants received FF/VI 100/25 µg OD in the evening,via a DPI, for a period of 12 weeks.
Mean Change From Baseline (BL) in Daily Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the 12-week Treatment Period	-11.8 Liters/minute (L/min) Standard Error 3.16	39.2 Liters/minute (L/min) Standard Error 3.14

SECONDARY outcome

Timeframe: Baseline and Weeks 1-12 (up to Day 84)

Population: ITT Population. Only those participants who had AM PEF data for at least 2 days in the Baseline week prior to randomization and at least 2 days after randomization and were available at the indicated time point were assessed.

PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline was calculated as the value of the averaged daily AM PEF over the 12-week Treatment Period minus the Baseline value. A Repeated Measures analysis adjusted for Baseline, region, sex, age, treatment, week, week by Baseline interaction, and week by treatment interaction was used.

Outcome measures

Outcome measures
Measure	Placebo n=153 Participants Participants received placebo OD in the evening,via a DPI, for a period of 12 weeks.	Fluticasone Furoate/Vilanterol 100/25 µg Once Daily n=153 Participants Participants received FF/VI 100/25 µg OD in the evening,via a DPI, for a period of 12 weeks.
Mean Change From Baseline in Daily Morning (AM) PEF Averaged Over the 12-week Treatment Period	-9.3 L/min Standard Error 3.12	43.6 L/min Standard Error 3.12

SECONDARY outcome

Timeframe: Baseline and Weeks 1-12 (up to Day 84)

Population: ITT Population

The number of inhalations of rescue albuterol/salbutamol inhalation aerosol (medication used to relieve symptoms immediately) used during the day and night was recorded by the participants in a daily diary. A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication was considered as rescue free. Participants who were rescue free for 24-hour periods during the 12-week Treatment Period were assessed. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline is calculated as the average value during the 12-week Treatment Period minus the value at Baseline. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.

Outcome measures

Outcome measures
Measure	Placebo n=154 Participants Participants received placebo OD in the evening,via a DPI, for a period of 12 weeks.	Fluticasone Furoate/Vilanterol 100/25 µg Once Daily n=153 Participants Participants received FF/VI 100/25 µg OD in the evening,via a DPI, for a period of 12 weeks.
Mean Change From Baseline in the Percentage of Rescue-free 24- Hour (hr) Periods During the 12-week Treatment Period	8.3 Percentage of rescue-free 24-hr periods Standard Error 2.59	30.1 Percentage of rescue-free 24-hr periods Standard Error 2.60

SECONDARY outcome

Timeframe: Baseline and Weeks 1-12 (up to Day 84)

Population: ITT Population

Asthma symptoms were recorded in a daily diary by the participants every day in the morning and evening before taking any rescue or study medication and before PEF measurement. A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no symptoms was considered as symptom free. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Participants who were symptom free for 24-hour periods during the 12-week Treatment Period were assessed. Change from Baseline is calculated as the average value during the 12-week Treatment Period minus the value at Baseline. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.

Outcome measures

Outcome measures
Measure	Placebo n=154 Participants Participants received placebo OD in the evening,via a DPI, for a period of 12 weeks.	Fluticasone Furoate/Vilanterol 100/25 µg Once Daily n=153 Participants Participants received FF/VI 100/25 µg OD in the evening,via a DPI, for a period of 12 weeks.
Mean Change From Baseline in the Percentage of Symptom-free 24- Hour (hr) Periods During the 12-week Treatment Period	9.0 Percentage of symptom-free 24-hr periods Standard Error 2.30	24.8 Percentage of symptom-free 24-hr periods Standard Error 2.31

SECONDARY outcome

Timeframe: Baseline and Week 12

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

The AQLQ is a disease-specific, self-administered quality of life questionnaire developed to evaluate the impact of asthma treatments on the quality of life of asthma sufferers. The AQLQ contains 32 items in 4 domains: activity limitation (11 items), symptoms (12 items), emotional function (5 items), and environmental stimuli (4 items). The 32 items of the questionnaire are averaged to produce one overall quality of life score. The response format consists of a 7-point scale, where a value of 1 indicates "total impairment" and a value of 7 indicates "no impairment." Change from Baseline was calculated as the Week 12 value minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.

Outcome measures

Outcome measures
Measure	Placebo n=71 Participants Participants received placebo OD in the evening,via a DPI, for a period of 12 weeks.	Fluticasone Furoate/Vilanterol 100/25 µg Once Daily n=135 Participants Participants received FF/VI 100/25 µg OD in the evening,via a DPI, for a period of 12 weeks.
Change From Baseline in Total Asthma Quality of Life Questionnaire (AQLQ) Score at Week 12	0.33 Scores on a scale Standard Error 0.094	0.84 Scores on a scale Standard Error 0.068

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Fluticasone Furoate/Vilanterol 100/25 µg Once Daily

Serious events: 2 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=154 participants at risk Participants received placebo OD in the evening,via a DPI, for a period of 12 weeks.	Fluticasone Furoate/Vilanterol 100/25 µg Once Daily n=153 participants at risk Participants received FF/VI 100/25 µg OD in the evening,via a DPI, for a period of 12 weeks.
Cardiac disorders Atrial fibrillation	0.00% 0/154 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow up (up to Study Day 91). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received \>=1 dose of trial medication.	0.65% 1/153 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow up (up to Study Day 91). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received \>=1 dose of trial medication.
Gastrointestinal disorders Enteritis	0.00% 0/154 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow up (up to Study Day 91). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received \>=1 dose of trial medication.	0.65% 1/153 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow up (up to Study Day 91). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received \>=1 dose of trial medication.

Other adverse events

Other adverse events
Measure	Placebo n=154 participants at risk Participants received placebo OD in the evening,via a DPI, for a period of 12 weeks.	Fluticasone Furoate/Vilanterol 100/25 µg Once Daily n=153 participants at risk Participants received FF/VI 100/25 µg OD in the evening,via a DPI, for a period of 12 weeks.
Infections and infestations Upper respiratory tract infection	9.1% 14/154 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow up (up to Study Day 91). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received \>=1 dose of trial medication.	7.2% 11/153 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow up (up to Study Day 91). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received \>=1 dose of trial medication.
Infections and infestations Nasopharyngitis	8.4% 13/154 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow up (up to Study Day 91). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received \>=1 dose of trial medication.	4.6% 7/153 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow up (up to Study Day 91). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received \>=1 dose of trial medication.
Nervous system disorders Headache	1.9% 3/154 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow up (up to Study Day 91). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received \>=1 dose of trial medication.	4.6% 7/153 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow up (up to Study Day 91). SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received \>=1 dose of trial medication.

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.
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