Trial Outcomes & Findings for Clinical Study Evaluating Safety and Efficacy of Fluticasone Furoate in People With Asthma (NCT NCT01436071)

NCT ID: NCT01436071

Last Updated: 2017-01-11

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. Evening clinic visit FEV1 is defined as the clinic visit (pre-bronchodilator and pre-dose) FEV1 measurement taken at the Week 12 clinic visit. Pre-dose and pre-rescue albuterol/salbutamol trough FEV1 were measured electronically by spirometry in the evening at the Baseline through Week 12 clinic visits. The highest of 3 technically acceptable measurements was recorded. Baseline was the pre-dose value obtained at Visit 2. Change from Baseline was calculated as the Week 12 value minus the Baseline value. Analysis was performed using analysis of covariance (ANCOVA) with covariates of Baseline, region, sex, age, and treatment. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing, pre-dose, post-Baseline on-treatment measurement at scheduled clinic visits was used to impute the missing value.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 248 participants
• Primary outcome timeframe: Baseline and Week 12
• Results posted on: 2017-01-11

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 were then randomized to a 12-week Treatment Period. A total of 449 participants were screened; 248 were randomized, and 242 received >=1 dose of study treatment.

Participant milestones

Measure	Placebo Participants receieved placebo via a Dry Powder Inhaler (DPI) once daily (OD) in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 50 µg OD Participants received fluticasone furoate (FF) 50 micrograms (µg) inhalation powder via a DPI OD in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
Overall Study STARTED	124	124
Overall Study Safety Population	121	121
Overall Study COMPLETED	98	110
Overall Study NOT COMPLETED	26	14

Reasons for withdrawal

Measure	Placebo Participants receieved placebo via a Dry Powder Inhaler (DPI) once daily (OD) in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 50 µg OD Participants received fluticasone furoate (FF) 50 micrograms (µg) inhalation powder via a DPI OD in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
Overall Study Adverse Event	1	0
Overall Study Lack of Efficacy	16	7
Overall Study Protocol Violation	0	1
Overall Study Lost to Follow-up	3	1
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Subject	2	2
Overall Study Did Not Receive Trial Medication	3	3

Baseline Characteristics

Clinical Study Evaluating Safety and Efficacy of Fluticasone Furoate in People With Asthma

Baseline characteristics by cohort

Measure	Placebo n=121 Participants Participants receieved placebo via a Dry Powder Inhaler (DPI) once daily (OD) in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 50 µg OD n=121 Participants Participants received fluticasone furoate (FF) 50 micrograms (µg) inhalation powder via a DPI OD in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	Total n=242 Participants Total of all reporting groups
Age, Continuous	33.5 Years STANDARD_DEVIATION 13.81 • n=93 Participants	36.8 Years STANDARD_DEVIATION 15.98 • n=4 Participants	35.2 Years STANDARD_DEVIATION 14.99 • n=27 Participants
Gender Female	75 Participants n=93 Participants	70 Participants n=4 Participants	145 Participants n=27 Participants
Gender Male	46 Participants n=93 Participants	51 Participants n=4 Participants	97 Participants n=27 Participants
Race/Ethnicity, Customized African American/African Heritage	6 Participants n=93 Participants	7 Participants n=4 Participants	13 Participants n=27 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	59 Participants n=93 Participants	46 Participants n=4 Participants	105 Participants n=27 Participants
Race/Ethnicity, Customized Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized White	32 Participants n=93 Participants	44 Participants n=4 Participants	76 Participants n=27 Participants
Race/Ethnicity, Customized African American/African Heritage & White	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Race/Ethnicity, Customized American Indian or Alaska Native & White	21 Participants n=93 Participants	24 Participants n=4 Participants	45 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-Treat (ITT) Population: all participants (par.) randomized to treatment who received \>=1 dose of study medication, except for the par. of one investigator (excluded after good clinical practice \[GCP\] issues identified during a site audit). Only those par. with non-missing covariates and a post-Baseline FEV1 measurement 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. Evening clinic visit FEV1 is defined as the clinic visit (pre-bronchodilator and pre-dose) FEV1 measurement taken at the Week 12 clinic visit. Pre-dose and pre-rescue albuterol/salbutamol trough FEV1 were measured electronically by spirometry in the evening at the Baseline through Week 12 clinic visits. The highest of 3 technically acceptable measurements was recorded. Baseline was the pre-dose value obtained at Visit 2. Change from Baseline was calculated as the Week 12 value minus the Baseline value. Analysis was performed using analysis of covariance (ANCOVA) with covariates of Baseline, region, sex, age, and treatment. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing, pre-dose, post-Baseline on-treatment measurement at scheduled clinic visits was used to impute the missing value.

Outcome measures

Measure	Placebo n=106 Participants Participants receieved placebo via a Dry Powder Inhaler (DPI) once daily (OD) in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 50 µg OD n=108 Participants Participants received fluticasone furoate (FF) 50 micrograms (µg) inhalation powder via a DPI OD in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
Change From Baseline in Clinic Visit Evening (Pre-bronchodilator and Pre-dose) Forced Expiratory Volume in One Second (FEV1) at the End of the 12-week Treatment Period	0.038 Liters Standard Error 0.0333	0.157 Liters Standard Error 0.0330

SECONDARY outcome

Timeframe: From Baseline up to Week 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The number of inhalations of rescue bronchodilator, albuterol/salbutamol inhalation aerosol, used during the day and night was recorded by the participants in a daily electronic diary (eDiary). 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 to be rescue free. A 24-hour period was considered as missing if both day time and night time values were missing or if one of the day time or night time values were missing and the other value indicated no use of rescue medication. The Baseline value is the average of the values over the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.

Outcome measures

Measure	Placebo n=110 Participants Participants receieved placebo via a Dry Powder Inhaler (DPI) once daily (OD) in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 50 µg OD n=111 Participants Participants received fluticasone furoate (FF) 50 micrograms (µg) inhalation powder via a DPI OD in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods Over the 12-week Treatment Period	17.1 Percentage of rescue-free 24-hr periods Standard Error 2.78	28.7 Percentage of rescue-free 24-hr periods Standard Error 2.77

SECONDARY outcome

Timeframe: From Baseline up to Week 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

PEF is a measure of lung function and is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each morning and evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Change from Baseline (defined as the average of the values of the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily trough PM PEF over the 12-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.

Outcome measures

Measure	Placebo n=110 Participants Participants receieved placebo via a Dry Powder Inhaler (DPI) once daily (OD) in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 50 µg OD n=111 Participants Participants received fluticasone furoate (FF) 50 micrograms (µg) inhalation powder via a DPI OD in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
Change From Baseline in Daily Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the 12-week Treatment Period	19.5 Liters/minute (L/min) Standard Error 3.72	22.8 Liters/minute (L/min) Standard Error 3.70

SECONDARY outcome

Timeframe: From Baseline up to Week 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

PEF is a measure of lung function and is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each morning and evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Change from Baseline (defined as the average of the values of the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily AM PEF over the 12-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.

Outcome measures

Measure	Placebo n=110 Participants Participants receieved placebo via a Dry Powder Inhaler (DPI) once daily (OD) in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 50 µg OD n=111 Participants Participants received fluticasone furoate (FF) 50 micrograms (µg) inhalation powder via a DPI OD in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
Change From Baseline in Daily Morning (AM) PEF Averaged Over the 12-week Treatment Period	22.9 L/min Standard Error 3.65	34.5 L/min Standard Error 3.64

SECONDARY outcome

Timeframe: From Baseline up to Week 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Asthma symptoms were recorded in a daily eDairy by the participants every day in the morning and evening before taking any rescue or study medication and before the peak expiratory flow measurement. A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no symptoms was considered to be symptom free. A 24-hour period was considered as missing if both the day time and night time data were missing or if one was symptom-free but the other was missing. The Baseline value was the average of the values of the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 12-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.

Outcome measures

Measure	Placebo n=110 Participants Participants receieved placebo via a Dry Powder Inhaler (DPI) once daily (OD) in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 50 µg OD n=111 Participants Participants received fluticasone furoate (FF) 50 micrograms (µg) inhalation powder via a DPI OD in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods Over the 12-week Treatment Period	14.0 Percentage of symptom-free 24-hr periods Standard Error 2.49	22.6 Percentage of symptom-free 24-hr periods Standard Error 2.47

SECONDARY outcome

Timeframe: From the first dose of the study medication until Week 12/Early Withdrawal

Population: ITT Population

The reason for withdrawal was lack of efficacy if a participant was withdrawn due to: clinic FEV1 falling below the FEV1 stability limit; participant experiencing at least 4 days of AM or PM PEF falling below the PEF stability limit and/or at least 3 days of >=12 inhalations/day of albuterol/salbutamol usage during the 7 days immediately preceding any contact; or the occurrence of an asthma exacerbation, defined as the deterioration of asthma requiring the use of systemic (oral, parenteral, or depot) corticosteroids for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. The FEV1 stability limit was calculated as the best pre-salbutamol/albuterol FEV1 at Visit 2 * 80%. The PEF stability limit was calculated as the mean AM PEF from the available 7 consecutive days preceding Visit 2 * 80%.

Outcome measures

Measure	Placebo n=111 Participants Participants receieved placebo via a Dry Powder Inhaler (DPI) once daily (OD) in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 50 µg OD n=111 Participants Participants received fluticasone furoate (FF) 50 micrograms (µg) inhalation powder via a DPI OD in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
Number of Participants Who Withdrew Due to a Lack of Efficacy During the 12-week Treatment Period	15 Participants	7 Participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 27 other events

Deaths: 0 deaths

FF 50 µg OD

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=121 participants at risk Participants receieved placebo via a Dry Powder Inhaler (DPI) once daily (OD) in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 50 µg OD n=121 participants at risk Participants received fluticasone furoate (FF) 50 micrograms (µg) inhalation powder via a DPI OD in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
Infections and infestations Appendicitis perforated	0.00% 0/121 • On-treatment adverse events (AEs), defined as those events occurring while participants were on treatment, up to and including the day after the last dose (up to 12 weeks), are reported. Serious AEs (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.83% 1/121 • On-treatment adverse events (AEs), defined as those events occurring while participants were on treatment, up to and including the day after the last dose (up to 12 weeks), are reported. Serious AEs (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Injury, poisoning and procedural complications Multiple injuries	0.83% 1/121 • On-treatment adverse events (AEs), defined as those events occurring while participants were on treatment, up to and including the day after the last dose (up to 12 weeks), are reported. Serious AEs (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/121 • On-treatment adverse events (AEs), defined as those events occurring while participants were on treatment, up to and including the day after the last dose (up to 12 weeks), are reported. Serious AEs (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.

Other adverse events

Measure	Placebo n=121 participants at risk Participants receieved placebo via a Dry Powder Inhaler (DPI) once daily (OD) in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.	FF 50 µg OD n=121 participants at risk Participants received fluticasone furoate (FF) 50 micrograms (µg) inhalation powder via a DPI OD in the evening for 12 weeks. In addition, all participants were provided with albuterol/salbutamol aerosol to be used as rescue medication as needed.
Infections and infestations Nasopharyngitis	4.1% 5/121 • On-treatment adverse events (AEs), defined as those events occurring while participants were on treatment, up to and including the day after the last dose (up to 12 weeks), are reported. Serious AEs (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	5.8% 7/121 • On-treatment adverse events (AEs), defined as those events occurring while participants were on treatment, up to and including the day after the last dose (up to 12 weeks), are reported. Serious AEs (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Infections and infestations Pharyngitis	5.0% 6/121 • On-treatment adverse events (AEs), defined as those events occurring while participants were on treatment, up to and including the day after the last dose (up to 12 weeks), are reported. Serious AEs (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	5.0% 6/121 • On-treatment adverse events (AEs), defined as those events occurring while participants were on treatment, up to and including the day after the last dose (up to 12 weeks), are reported. Serious AEs (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Infections and infestations Influenza	3.3% 4/121 • On-treatment adverse events (AEs), defined as those events occurring while participants were on treatment, up to and including the day after the last dose (up to 12 weeks), are reported. Serious AEs (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.83% 1/121 • On-treatment adverse events (AEs), defined as those events occurring while participants were on treatment, up to and including the day after the last dose (up to 12 weeks), are reported. Serious AEs (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Nervous system disorders Headache	11.6% 14/121 • On-treatment adverse events (AEs), defined as those events occurring while participants were on treatment, up to and including the day after the last dose (up to 12 weeks), are reported. Serious AEs (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	5.0% 6/121 • On-treatment adverse events (AEs), defined as those events occurring while participants were on treatment, up to and including the day after the last dose (up to 12 weeks), are reported. Serious AEs (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study 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.
• Publication restrictions are in place

Restriction type: OTHER