Trial Outcomes & Findings for To Investigate the Effects of Altering the Time of Day of Dosing (Morning or Evening) With Fluticasone Furoate 100 Micrograms Once Daily Administered Via a Dry Powder Inhaler in Subjects With Asthma (NCT NCT01808339)

Last Updated: 2017-01-09

Results Overview

FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured using site equipment (KoKo Pneumotach Spirometer). Weighted mean FEV1 was calculated using the Day 14 24-hour serial FEV1 measurements taken at 3, 6, 9, 12, 15, 18, 21, and 24 hours post-dose (measured in the evening of Day 15). At each time point, the highest of three technically acceptable measurements was recorded. FEV1 weighted mean was analyzed using a mixed effects analysis of a covariance model with fixed effect terms for treatment and period, participant Baseline, period Baseline, gender, and age as covariates, and participant as a random effect.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

24 hours post-PM dose on Day 14 of each treatment period (up to Study Day 105)

Results posted on

2017-01-09

Participant Flow

Participants meeting eligibility criteria at the Screening visit entered a 2-week Run-in Period for Baseline safety evaluations and to obtain measures of asthma status.

Participants meeting randomization criteria were enrolled in the study for 13-18 weeks: three 14-day treatment periods separated by a 14- to 21-day washout period, followed by a follow-up visit within 7-14 days of the last dose.

Participant milestones

Participant milestones
Measure	FF 100 µg AM /FF 100 µg PM/Placebo Participants received 3 treatments (A, B, and C) in sequence ABC. During treatment A participants received fluticasone furoate (FF) 100 micrograms (100 µg) in the morning (AM) at approximately 09:00 and received placebo in the evening (PM) at approximately 21:00 for 14 days (+/-2 days) via a dry powder inhaler (DPI). During treatment B participants received placebo in the AM and FF 100 µg in the PM for 14 days (+/-2 days) via a DPI. During treatment C participants received placebo via a DPI for 14 days (+/-2 days) in the AM and PM. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 100 µg AM/Placebo/FF 100 µg PM Participants received 3 treatments (A, B, and C) in sequence ACB. During treatment A participants received FF 100 µg in the AM at approximately 09:00 and received placebo in the PM at approximately 21:00 for 14 days (+/-2 days) via a DPI. During treatment B participants received placebo in the AM and FF 100 µg in the PM for 14 days (+/-2 days) via a DPI. During treatment C participants received placebo via a DPI for 14 days (+/-2 days) in the AM and PM. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 100 µg PM /FF 100 µg AM/Placebo Participants received 3 treatments (A, B, and C) in sequence BAC. During treatment A participants received FF 100 µg in the AM at approximately 09:00 and received placebo in the PM at approximately 21:00 for 14 days (+/-2 days) via a DPI. During treatment B participants received placebo in the AM and FF 100 µg in the PM for 14 days (+/-2 days) via a DPI. During treatment C participants received placebo via a DPI for 14 days (+/-2 days) in the AM and PM. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 100 µg PM /Placebo/FF 100 µg AM Participants received 3 treatments (A, B, and C) in sequence BCA. During treatment A participants received FF 100 µg in the AM at approximately 09:00 and received placebo in the PM at approximately 21:00 for 14 days (+/-2 days) via a DPI. During treatment B participants received placebo in the AM and FF 100 µg in the PM for 14 days (+/-2 days) via a DPI. During treatment C participants received placebo via a DPI for 14 days (+/-2 days) in the AM and PM. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	Placebo/FF 100 µg AM/FF 100 µg PM Participants received 3 treatments (A, B, and C) in sequence CAB. During treatment A participants received FF 100 µg in the AM at approximately 09:00 and received placebo in the PM at approximately 21:00 for 14 days (+/-2 days) via a DPI. During treatment B participants received placebo in the AM and FF 100 µg in the PM for 14 days (+/-2 days) via a DPI. During treatment C participants received placebo via a DPI for 14 days (+/-2 days) in the AM and PM. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	Placebo/FF 100 µg PM /FF 100 µg AM Participants received 3 treatments (A, B, and C) in sequence CBA. During treatment A participants received FF 100 µg in the AM at approximately 09:00 and received placebo in the PM at approximately 21:00 for 14 days (+/-2 days) via a DPI. During treatment B participants received placebo in the AM and FF 100 µg in the PM for 14 days (+/-2 days) via a DPI. During treatment C participants received placebo via a DPI for 14 days (+/-2 days) in the AM and PM. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
Treatment Period 1 (14 Days) STARTED	4	4	4	4	6	6
Treatment Period 1 (14 Days) COMPLETED	4	3	4	2	4	5
Treatment Period 1 (14 Days) NOT COMPLETED	0	1	0	2	2	1
Washout Period 1 (14-21 Days) STARTED	4	3	4	2	4	5
Washout Period 1 (14-21 Days) COMPLETED	4	3	4	2	4	5
Washout Period 1 (14-21 Days) NOT COMPLETED	0	0	0	0	0	0
Treatment Period 2 (14 Days) STARTED	4	3	4	2	4	5
Treatment Period 2 (14 Days) COMPLETED	4	3	4	2	4	5
Treatment Period 2 (14 Days) NOT COMPLETED	0	0	0	0	0	0
Washout Period 2 (14-21 Days) STARTED	4	3	4	2	4	5
Washout Period 2 (14-21 Days) COMPLETED	4	3	4	2	4	5
Washout Period 2 (14-21 Days) NOT COMPLETED	0	0	0	0	0	0
Treatment Period 3 (14 Days) STARTED	4	3	4	2	4	5
Treatment Period 3 (14 Days) COMPLETED	4	3	3	2	4	5
Treatment Period 3 (14 Days) NOT COMPLETED	0	0	1	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	FF 100 µg AM/Placebo/FF 100 µg PM Participants received 3 treatments (A, B, and C) in sequence ACB. During treatment A participants received FF 100 µg in the AM at approximately 09:00 and received placebo in the PM at approximately 21:00 for 14 days (+/-2 days) via a DPI. During treatment B participants received placebo in the AM and FF 100 µg in the PM for 14 days (+/-2 days) via a DPI. During treatment C participants received placebo via a DPI for 14 days (+/-2 days) in the AM and PM. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 100 µg PM /FF 100 µg AM/Placebo Participants received 3 treatments (A, B, and C) in sequence BAC. During treatment A participants received FF 100 µg in the AM at approximately 09:00 and received placebo in the PM at approximately 21:00 for 14 days (+/-2 days) via a DPI. During treatment B participants received placebo in the AM and FF 100 µg in the PM for 14 days (+/-2 days) via a DPI. During treatment C participants received placebo via a DPI for 14 days (+/-2 days) in the AM and PM. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 100 µg PM /Placebo/FF 100 µg AM Participants received 3 treatments (A, B, and C) in sequence BCA. During treatment A participants received FF 100 µg in the AM at approximately 09:00 and received placebo in the PM at approximately 21:00 for 14 days (+/-2 days) via a DPI. During treatment B participants received placebo in the AM and FF 100 µg in the PM for 14 days (+/-2 days) via a DPI. During treatment C participants received placebo via a DPI for 14 days (+/-2 days) in the AM and PM. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	Placebo/FF 100 µg AM/FF 100 µg PM Participants received 3 treatments (A, B, and C) in sequence CAB. During treatment A participants received FF 100 µg in the AM at approximately 09:00 and received placebo in the PM at approximately 21:00 for 14 days (+/-2 days) via a DPI. During treatment B participants received placebo in the AM and FF 100 µg in the PM for 14 days (+/-2 days) via a DPI. During treatment C participants received placebo via a DPI for 14 days (+/-2 days) in the AM and PM. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	Placebo/FF 100 µg PM /FF 100 µg AM Participants received 3 treatments (A, B, and C) in sequence CBA. During treatment A participants received FF 100 µg in the AM at approximately 09:00 and received placebo in the PM at approximately 21:00 for 14 days (+/-2 days) via a DPI. During treatment B participants received placebo in the AM and FF 100 µg in the PM for 14 days (+/-2 days) via a DPI. During treatment C participants received placebo via a DPI for 14 days (+/-2 days) in the AM and PM. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
Treatment Period 1 (14 Days) Met Protocol-defined Stopping Criteria	0	0	1	2	1
Treatment Period 1 (14 Days) Withdrawal by Subject	1	0	1	0	0
Treatment Period 3 (14 Days) Met Protocol-defined Stopping Criteria	0	1	0	0	0

Baseline Characteristics

To Investigate the Effects of Altering the Time of Day of Dosing (Morning or Evening) With Fluticasone Furoate 100 Micrograms Once Daily Administered Via a Dry Powder Inhaler in Subjects With Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FF 100 µg AM/FF 100 µg PM/Placebo n=28 Participants Participants received 3 treatments (A, B, and C) in either of the six sequences: ABC , ACB, BAC, BCA, CAB, or CBA. During treatment A participants received fluticasone furoate (FF) 100 micrograms (100 µg) in the morning (AM) at approximately 09:00 and received placebo in the evening (PM) at approximately 21:00 for 14 days (+/-2 days) via a dry powder inhaler (DPI), during treatment B: participants received placebo in the AM and FF 100 µg in the PM for 14 days (+/-2 days) via a DPI during treatment C: participants received placebo via a DPI for 14 days (+/-2 days) in the AM and PM. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
Age, Continuous	31.7 Years STANDARD_DEVIATION 10.99 • n=5 Participants
Gender Female	15 Participants n=5 Participants
Gender Male	13 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	1 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	21 Participants n=5 Participants
Race/Ethnicity, Customized White - Mixed Race	1 Participants n=5 Participants
Race/Ethnicity, Customized Mixed Race	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 hours post-PM dose on Day 14 of each treatment period (up to Study Day 105)

Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of study medication, and had at least one Baseline and post-dose FEV1 measurement performed. Only those participants with non-missing covariates and a post-Baseline FEV1 measurement were analyzed.

Outcome measures

Outcome measures
Measure	FF 100 µg AM n=21 Participants Participants received fluticasone furoate (FF) 100 micrograms (100 µg) in the morning (AM) at approximately 09:00 and received placebo in the evening (PM) at approximately 21:00 for 14 days (+/-2 days) via a dry powder inhaler (DPI) in one of the three treatment periods. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 100 µg PM n=22 Participants Participants received placebo in the AM at approximately 09:00 and FF 100 µg in the PM at approximately 21:00 for 14 days (+/-2 days) via a DPI in one of the three treatment periods. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	Placebo n=22 Participants Participants received placebo via a DPI for 14 days (+/-2 days) in the AM and PM. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
Weighted Mean Forced Expiratory Volume in 1 Second (FEV1) Measured Over 24 Hours at Day 14 of Each Treatment Period	3.303 Liters Standard Error 0.0589	3.332 Liters Standard Error 0.0584	3.227 Liters Standard Error 0.0585

SECONDARY outcome

Timeframe: Day 14 of each treatment period (up to Study Day 105)

Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of study medication, and had at least one Baseline and post-dose FEV1 measurement performed. Only those participants available at the specified time points were analyzed

FEV1 is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured using site equipment (KoKo Pneumotach Spirometer). FEV1 PM trough FEV1 values were the values taken pre-treatment on Day 14, and AM trough FEV1 values were the values taken pre-treatment on Day 15 in each treatment period; thus, there is only one value (pre-treatment record) per period for AM and PM trough.

Outcome measures

Outcome measures
Measure	FF 100 µg AM n=21 Participants Participants received fluticasone furoate (FF) 100 micrograms (100 µg) in the morning (AM) at approximately 09:00 and received placebo in the evening (PM) at approximately 21:00 for 14 days (+/-2 days) via a dry powder inhaler (DPI) in one of the three treatment periods. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 100 µg PM n=22 Participants Participants received placebo in the AM at approximately 09:00 and FF 100 µg in the PM at approximately 21:00 for 14 days (+/-2 days) via a DPI in one of the three treatment periods. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	Placebo n=22 Participants Participants received placebo via a DPI for 14 days (+/-2 days) in the AM and PM. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
Pre-treatment AM and PM Trough FEV1 on Day 14 of Each Treatment Period AM Trough FEV1	3.299 Liters Standard Error 0.0707	3.359 Liters Standard Error 0.0702	3.286 Liters Standard Error 0.0703
Pre-treatment AM and PM Trough FEV1 on Day 14 of Each Treatment Period PM Trough FEV1	3.236 Liters Standard Error 0.0607	3.290 Liters Standard Error 0.0598	3.177 Liters Standard Error 0.0600

SECONDARY outcome

Timeframe: Up to 18 weeks

Population: All Subjects Population: all participants who received at least one dose of study medication

An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs were collected from the start of dosing with investigational product and until follow-up.

Outcome measures

Outcome measures
Measure	FF 100 µg AM n=23 Participants Participants received fluticasone furoate (FF) 100 micrograms (100 µg) in the morning (AM) at approximately 09:00 and received placebo in the evening (PM) at approximately 21:00 for 14 days (+/-2 days) via a dry powder inhaler (DPI) in one of the three treatment periods. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 100 µg PM n=24 Participants Participants received placebo in the AM at approximately 09:00 and FF 100 µg in the PM at approximately 21:00 for 14 days (+/-2 days) via a DPI in one of the three treatment periods. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	Placebo n=25 Participants Participants received placebo via a DPI for 14 days (+/-2 days) in the AM and PM. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
Number of Participants With Any Adverse Event (AE)	18 Participants	18 Participants	16 Participants

SECONDARY outcome

Timeframe: Up to 18 weeks

PEF is a measure of lung function and is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. AM and PM pre-treatment PEF was measured throughout the study for the purposes of monitoring participants' asthma stability, and was measured from the start of the Run-in Period until completion of Treatment Period 3 (including during the washout periods), prior to study medication and/or any rescue albuterol/salbutamol inhalation aerosol use. The data collected were only assessed by the Investigator on an individual basis during the study and were not formally summarized or statistically analyzed; consequently, data are not reported.

Outcome measures

Outcome data not reported

Adverse Events

FF 100 µg AM

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

FF 100 µg PM

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

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