Trial Outcomes & Findings for Safety Study of the Effects of Inhaled Fluticasone Furoate/GW642444 on the Hypothalamic-Pituitary-Adrenal (HPA) Axis (NCT NCT01086410)

NCT ID: NCT01086410

Last Updated: 2017-01-18

Results Overview

Serum cortisol weighted mean was determined for each participant over the time period 0-12 hours on Day -1/1 (Baseline) and Day 42. Serum cortisol weighted mean was derived by dividing the area under the concentration-time curve (AUC; defined as thearea under the concentration-time curve from time zero up to 24 hours) by the sample collection time interval. The sample collection time interval is defined as the difference between the time of the last cortisol sample and the time of the first cortisol sample. Samples were collected at the following time points: 0 (first blood draw/pre-dose); 2, 4, 9, 12, 14, 16, 20, 22, and 24 hours (relative to the "0" time point). Because values are on a logged scale, the ratio of the endpoint to Baseline is presented, as it is a measure of the difference from Baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 185 participants
• Primary outcome timeframe: Day -1/1 (Baseline) and Day 42
• Results posted on: 2017-01-18

Participant Flow

Participants who met all the inclusion criteria entered a 7- to 14-day Run-in Period (screening visit [Visit 1]). Participants were provided with albuterol/salbutamol inhalation aerosol for relief of asthma symptoms during the study.

At the end of the Run-in Period, participants who meet the randomization criteria were admitted to the clinic in the evening (Visit 2) for the Baseline collection of 24-hour serial serum cortisol samples and urine. Eligible participants were randomly assigned to one of four treatment groups in a 4:4:4:1 ratio.

Participant milestones

Measure	Placebo Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Overall Study STARTED	58	56	56	15
Overall Study COMPLETED	55	54	55	13
Overall Study NOT COMPLETED	3	2	1	2

Reasons for withdrawal

Measure	Placebo Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Overall Study Adverse Event	1	0	0	2
Overall Study Lack of Efficacy	1	1	0	0
Overall Study Protocol Violation	1	1	0	0
Overall Study Lost to Follow-up	0	0	1	0

Baseline Characteristics

Safety Study of the Effects of Inhaled Fluticasone Furoate/GW642444 on the Hypothalamic-Pituitary-Adrenal (HPA) Axis

Baseline characteristics by cohort

Measure	Placebo n=58 Participants Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=56 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=56 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=15 Participants Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.	Total n=185 Participants Total of all reporting groups
Age, Continuous	36.1 Years STANDARD_DEVIATION 15.42 • n=93 Participants	34.4 Years STANDARD_DEVIATION 15.63 • n=4 Participants	34.0 Years STANDARD_DEVIATION 13.74 • n=27 Participants	37.5 Years STANDARD_DEVIATION 14.19 • n=483 Participants	35.1 Years STANDARD_DEVIATION 14.82 • n=36 Participants
Gender Female	27 Participants n=93 Participants	31 Participants n=4 Participants	23 Participants n=27 Participants	6 Participants n=483 Participants	87 Participants n=36 Participants
Gender Male	31 Participants n=93 Participants	25 Participants n=4 Participants	33 Participants n=27 Participants	9 Participants n=483 Participants	98 Participants n=36 Participants
Race/Ethnicity, Customized African American/African Heritage	3 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	4 Participants n=36 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	55 Participants n=93 Participants	56 Participants n=4 Participants	53 Participants n=27 Participants	15 Participants n=483 Participants	179 Participants n=36 Participants

PRIMARY outcome

Timeframe: Day -1/1 (Baseline) and Day 42

Population: Serum Cortisol (SC) Population: all participants in the Intent-to-Treat Population who did not have protocol deviations that were considered to affect the SC endpoint and whose serum samples were not considered to have confounding factors affecting results interpretation. Only those participant available at the specified time points were analzyed.

Serum cortisol weighted mean was determined for each participant over the time period 0-12 hours on Day -1/1 (Baseline) and Day 42. Serum cortisol weighted mean was derived by dividing the area under the concentration-time curve (AUC; defined as thearea under the concentration-time curve from time zero up to 24 hours) by the sample collection time interval. The sample collection time interval is defined as the difference between the time of the last cortisol sample and the time of the first cortisol sample. Samples were collected at the following time points: 0 (first blood draw/pre-dose); 2, 4, 9, 12, 14, 16, 20, 22, and 24 hours (relative to the "0" time point). Because values are on a logged scale, the ratio of the endpoint to Baseline is presented, as it is a measure of the difference from Baseline.

Outcome measures

Measure	Placebo n=52 Participants Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=50 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=53 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=13 Participants Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Ratio From Baseline of the Serum Cortisol Weighted Mean (0-24 Hours) on Day -1/1 (Baseline) and Day 42	0.99 ratio from Baseline Geometric Coefficient of Variation 29.6	0.99 ratio from Baseline Geometric Coefficient of Variation 40.0	0.96 ratio from Baseline Geometric Coefficient of Variation 27.2	0.32 ratio from Baseline Geometric Coefficient of Variation 72.9

SECONDARY outcome

Timeframe: Day -1/1 (Baseline) and Day 42

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

Area under the plasma drug concentration-time (AUC[0-24 hour]) curve from time zero (pre-dose) to the last time of quantifiable serum cortisol concentration at 24 hours post-dose on Day -1/1 (Baseline) and Day 42 was measured. AUC reflects the actual body exposure to drug over a specified period of time after administration of a dose. Samples were collected at the following times: 0 (immediately pre-dose inhaled study drug); post-dose at 5 minutes (min), 15 min, 30 min, and 1 hour (hr), 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, and 24 hr. Because values are on a logged scale, the ratio of the endpoint to Baseline is presented, as it is a measure of the difference from Baseline.

Outcome measures

Measure	Placebo n=52 Participants Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=50 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=53 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=13 Participants Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Ratio From Baseline of the Serum Cortisol Area Under the Concentration-time Curve (AUC) (0-24 Hour) on Day -1/1 (Baseline) and Day 42	0.99 ratio from Baseline Geometric Coefficient of Variation 29.6	0.99 ratio from Baseline Geometric Coefficient of Variation 40.1	0.97 ratio from Baseline Geometric Coefficient of Variation 27.2	0.32 ratio from Baseline Geometric Coefficient of Variation 71.9

SECONDARY outcome

Timeframe: Day -1/1 (Baseline) and Day 42

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

Serum cortisol trough is defined as the minimum value of serum cortisol measured over the 24-hour period. Samples were collected at the following times: 0 (immediately pre-dose inhaled study drug); post-dose at 5 minutes (min), 15 min, 30 min, and 1 hour (hr), 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, and 24 hr. Because values are on a logged scale, the ratio of the endpoint to Baseline is presented, as it is a measure of the difference from Baseline.

Outcome measures

Measure	Placebo n=52 Participants Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=51 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=53 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=13 Participants Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Ratio From Baseline of Serum Cortisol Trough (0-24 Hours) at Day -1/1 (Baseline) and Day 42	1.04 ratio from Baseline Geometric Coefficient of Variation 88.2	0.84 ratio from Baseline Geometric Coefficient of Variation 88.7	0.73 ratio from Baseline Geometric Coefficient of Variation 80.7	0.28 ratio from Baseline Geometric Coefficient of Variation 82.3

SECONDARY outcome

Timeframe: Day -1/1 (Baseline) and Day 42

Population: Urine Cortisol (UC) Population: all participants in the ITT Population who did not have protocol deviations that were considered to affect the urine cortisol endpoint and whose urine samples were not considered to have confounding factors that would affect the interpretation of the results.

A 24-hour urine sample was collected for the measurement of 24-hour urinary cortisol excretion at Day -1/1 (Baseline) and Day 42. Only those participants available at the specified time points were analyzed. Because values are on a logged scale, the ratio of the endpoint to Baseline is presented, as it is a measure of the difference from Baseline.

Outcome measures

Measure	Placebo n=49 Participants Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=47 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=53 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=12 Participants Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Ratio From Baseline of 0-24 Hour Urinary Free Cortisol Excretion on Day -1/1 (Baseline) and Day 42	0.87 ratio from Baseline Geometric Coefficient of Variation 77.923	1.03 ratio from Baseline Geometric Coefficient of Variation 110.952	0.92 ratio from Baseline Geometric Coefficient of Variation 96.312	0.40 ratio from Baseline Geometric Coefficient of Variation 204.433

SECONDARY outcome

Timeframe: Day 42

Population: Pharmacokinetic (PK) Population: all participants in the ITT Population for whom a pharmacokinetic sample was obtained and analyzed.

Plasma FF and VI Pharmacokinetic (PK) Concentration were estimates at the following time points:0 (immediately pre-dose inhaled study drug), and post-dose at 5 min, 15 min, 30 min, and 1 hr, 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, 24 hr on Day 42. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the Pharmacokinetic Population.

Outcome measures

Measure	Placebo Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=54 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=56 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Plasma FF and VI Pharmacokinetic (PK) Concentration FF, 0 hour, n=53, 54	—	3.57 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	10.02 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	—
Plasma FF and VI Pharmacokinetic (PK) Concentration FF, 5 minutes post-dose, n=51, 54	—	16.65 picograms per milliliter (pg/mL) Standard Deviation 10.191	25.55 picograms per milliliter (pg/mL) Standard Deviation 14.438	—
Plasma FF and VI Pharmacokinetic (PK) Concentration FF, 15 minutes post-dose, n=50, 54	—	16.35 picograms per milliliter (pg/mL) Standard Deviation 10.198	28.84 picograms per milliliter (pg/mL) Standard Deviation 14.441	—
Plasma FF and VI Pharmacokinetic (PK) Concentration FF, 30 minutes post-dose, n=52, 52	—	17.12 picograms per milliliter (pg/mL) Standard Deviation 10.583	30.68 picograms per milliliter (pg/mL) Standard Deviation 15.461	—
Plasma FF and VI Pharmacokinetic (PK) Concentration FF, 1 hour post-dose, n=54, 54	—	16.91 picograms per milliliter (pg/mL) Standard Deviation 9.637	30.07 picograms per milliliter (pg/mL) Standard Deviation 15.540	—
Plasma FF and VI Pharmacokinetic (PK) Concentration FF, 2 hours post-dose, n=51, 53	—	15.00 picograms per milliliter (pg/mL) Standard Deviation 9.272	30.20 picograms per milliliter (pg/mL) Standard Deviation 18.292	—
Plasma FF and VI Pharmacokinetic (PK) Concentration FF, 4 hours post-dose, n=54, 53	—	9.78 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	21.79 picograms per milliliter (pg/mL) Standard Deviation 11.597	—
Plasma FF and VI Pharmacokinetic (PK) Concentration FF, 9 hours post-dose, n=48, 52	—	6.20 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	15.99 picograms per milliliter (pg/mL) Standard Deviation 11.667	—
Plasma FF and VI Pharmacokinetic (PK) Concentration FF, 12 hours post-dose, n=51, 55	—	4.62 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	13.37 picograms per milliliter (pg/mL) Standard Deviation 9.670	—
Plasma FF and VI Pharmacokinetic (PK) Concentration FF, 16 hours post-dose, n=49, 52	—	2.55 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	11.73 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	—
Plasma FF and VI Pharmacokinetic (PK) Concentration FF, 20 hours post-dose, n=51, 51	—	1.74 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	9.28 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	—
Plasma FF and VI Pharmacokinetic (PK) Concentration FF, 24 hours post-dose, n=48, 53	—	1.55 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	7.58 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	—
Plasma FF and VI Pharmacokinetic (PK) Concentration VI, 0 hours, n=52, 54	—	2.57 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	7.95 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	—
Plasma FF and VI Pharmacokinetic (PK) Concentration VI, 5 minutes post-dose, n=50, 54	—	85.22 picograms per milliliter (pg/mL) Standard Deviation 70.582	90.54 picograms per milliliter (pg/mL) Standard Deviation 88.794	—
Plasma FF and VI Pharmacokinetic (PK) Concentration VI, 15 minutes post-dose, n=48, 55	—	62.94 picograms per milliliter (pg/mL) Standard Deviation 52.020	72.53 picograms per milliliter (pg/mL) Standard Deviation 55.271	—
Plasma FF and VI Pharmacokinetic (PK) Concentration VI, 30 minutes post-dose, n=51, 55	—	33.38 picograms per milliliter (pg/mL) Standard Deviation 33.932	36.88 picograms per milliliter (pg/mL) Standard Deviation 33.157	—
Plasma FF and VI Pharmacokinetic (PK) Concentration VI, 1 hour post-dose, n=52, 53	—	14.63 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	20.07 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	—
Plasma FF and VI Pharmacokinetic (PK) Concentration VI, 2 hours post-dose, n=52, 55	—	7.09 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	6.06 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	—
Plasma FF and VI Pharmacokinetic (PK) Concentration VI, 4 hours post-dose, n=52, 54	—	0.00 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	0.45 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	—
Plasma FF and VI Pharmacokinetic (PK) Concentration VI, 9 hours post-dose, n=52, 55	—	0.00 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	0.47 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	—
Plasma FF and VI Pharmacokinetic (PK) Concentration VI, 12 hours post-dose, n=52, 55	—	0.00 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	1.21 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	—
Plasma FF and VI Pharmacokinetic (PK) Concentration VI, 16 hours post-dose, n=51, 52	—	0.00 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	4.76 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	—
Plasma FF and VI Pharmacokinetic (PK) Concentration VI, 20 hours post-dose, n=50, 54	—	0.00 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	0.00 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	—
Plasma FF and VI Pharmacokinetic (PK) Concentration VI, 24 hours post-dose, n=52, 55	—	1.19 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	0.00 picograms per milliliter (pg/mL) Standard Deviation NA Values below 10 pg/mL are below the limit of quantification and are imputed. Standard deviation is not displayed if \>30% of values are imputed.	—

SECONDARY outcome

Timeframe: Day 42

Population: PK Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the PK Population.

Area under the plasma drug concentration-time (AUC[0-t]) curve from time zero (pre-dose) to the last time of quantifiable FF concentration and AUC(0-24) is the concentration time curve from zero (pre-dose) to 24 hours of quantifiable FF concentration on Day 42 was measured. AUC reflects the actual body exposure to drug over a specified period of time after administration of a dose. Samples were collected at the following times: 0 (immediately pre-dose inhaled study drug); post-dose at 5 minutes (min), 15 min, 30 min, and 1 hour (hr), 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, and 24 hr post-dose on Day 42.

Outcome measures

Measure	Placebo Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=54 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=56 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
AUC(0-t) and AUC(0-24) for FF on Day 42 AUC(0-t), n=54, 55	—	58.842 picograms*hour per milliliter (pg*hr/mL) Interval 37.706 to 91.825	221.694 picograms*hour per milliliter (pg*hr/mL) Interval 152.697 to 321.868	—
AUC(0-t) and AUC(0-24) for FF on Day 42 AUC(0-24), n=49, 53	—	NA picograms*hour per milliliter (pg*hr/mL) Data are not available because \>=50% of values were non-calculable due to non-quantifiable concentrations (below the level of detection).	324.015 picograms*hour per milliliter (pg*hr/mL) Interval 267.233 to 392.862	—

SECONDARY outcome

Timeframe: Day 42

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

Cmax is defined as the maximum observed concentration on Day 42. Samples were collected at the following times: 0 (immediately pre-dose inhaled study drug); post-dose at 5 minutes (min), 15 min, 30 min, and 1 hour (hr), 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, and 24 hr post-dose on Day 42.

Outcome measures

Measure	Placebo Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=54 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=55 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Cmax for FF on Day 42	—	19.388 picograms per milliliter (pg/mL) Interval 16.796 to 22.379	33.017 picograms per milliliter (pg/mL) Interval 28.586 to 38.135	—

SECONDARY outcome

Timeframe: Day 42

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

tmax is defined as the time to reach the observed maximum concentration, and tlast is defined as the time of the last observed quantifiable concentration on Day 42. Samples were collected at the following times: 0 (immediately pre-dose inhaled study drug); post-dose at 5 minutes (min), 15 min, 30 min, and 1hour (hr), 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, and 24 hr post-dose on Day 42.

Outcome measures

Measure	Placebo Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=54 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=55 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Tmax and Tlast of FF at Day 42 tmax	—	0.500 hours Interval 0.03 to 8.97	0.500 hours Interval 0.07 to 4.0	—
Tmax and Tlast of FF at Day 42 tlast	—	9.000 hours Interval 0.98 to 24.0	20.042 hours Interval 0.95 to 24.08	—

SECONDARY outcome

Timeframe: Day 42

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

Area under the concentration-time (AUC[0-t]) curve from time zero (pre-dose) to the last time of quantifiable VI concentration on Day 42 was measured. Samples were collected at the following times: 0 (immediately pre-dose inhaled study drug); post-dose at 5 minutes (min), 15 min, 30 min, and 1 hour (hr), 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, and 24 hr post-dose on Day 42.

Outcome measures

Measure	Placebo Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=52 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=55 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
AUC(0-t) for VI on Day 42	—	41.177 picograms*hour per milliliter (pg*hr/mL) Standard Deviation 53.9720	66.937 picograms*hour per milliliter (pg*hr/mL) Standard Deviation 142.3461	—

SECONDARY outcome

Timeframe: Day 42

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

Cmax is defined as the maximum observed concentration on Day 42. Samples were collected at the following times: 0 (immediately pre-dose inhaled study drug); post-dose at 5 minutes (min), 15 min, 30 min, and 1 hour (hr), 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, and 24 hr post-dose on Day 42.

Outcome measures

Measure	Placebo Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=52 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=55 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Cmax for VI on Day 42	—	101.227 picograms per milliliter (pg/mL) Standard Deviation 73.8233	118.531 picograms per milliliter (pg/mL) Standard Deviation 86.8659	—

SECONDARY outcome

Timeframe: Day 42

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

tmax is defined as the time to reach the observed maximum concentration, and tlast is defined as the time of the last observed quantifiable VI concentration on Day 42. Samples were collected at the following times: 0 (immediately pre-dose inhaled study drug); post-dose at 5 minutes (min), 15 min, 30 min, and 1hour (hr), 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, and 24 hr post-dose on Day 42.

Outcome measures

Measure	Placebo Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=52 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=55 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Tmax and Tlast of VI at Day 42 tmax	—	0.083 hours Interval 0.0 to 2.0	0.083 hours Interval 0.0 to 16.0	—
Tmax and Tlast of VI at Day 42 tlast	—	0.500 hours Interval 0.03 to 2.0	0.950 hours Interval 0.08 to 16.0	—

SECONDARY outcome

Timeframe: From the start of study medication until Day 42 (Visit 5)/Early Withdrawal

Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of study drug.

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General Adverse AE/SAE module for a complete list of AEs and SAEs.

Outcome measures

Measure	Placebo n=58 Participants Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=56 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=56 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=15 Participants Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period Any AE	16 Participants	23 Participants	21 Participants	5 Participants
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period Any SAE	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Day 42/Early Withdrawal (EW)

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, and segmented neutrophils at Baseline and Day 42/EW. For all laboratory assessments, Baseline is the most recent recorded value at Screening or prior to Day -1/1. Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.

Outcome measures

Measure	Placebo n=58 Participants Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=56 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=56 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=15 Participants Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Change From Baseline in Basophil, Eosinophil, Lymphocyte, Monocyte, and Segmented Neutrophil Values at Day 42/Early Withdrawal (EW) Segmented Neutrophils, EW, n=2, 2, 0, 0	-2.30 Percentage Standard Deviation 11.738	-0.85 Percentage Standard Deviation 3.465	NA Percentage Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Percentage Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Basophil, Eosinophil, Lymphocyte, Monocyte, and Segmented Neutrophil Values at Day 42/Early Withdrawal (EW) Basophils, Day 42, n=50, 47, 53, 11	0.05 Percentage Standard Deviation 0.354	0.04 Percentage Standard Deviation 0.356	-0.05 Percentage Standard Deviation 0.350	-0.08 Percentage Standard Deviation 0.223
Change From Baseline in Basophil, Eosinophil, Lymphocyte, Monocyte, and Segmented Neutrophil Values at Day 42/Early Withdrawal (EW) Basophils, EW, n=2, 2, 0, 0	-0.10 Percentage Standard Deviation 0.141	0.10 Percentage Standard Deviation 0.141	NA Percentage Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Percentage Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Basophil, Eosinophil, Lymphocyte, Monocyte, and Segmented Neutrophil Values at Day 42/Early Withdrawal (EW) Eosinophils, Day 42, n=50, 47, 53, 11	0.57 Percentage Standard Deviation 2.837	0.27 Percentage Standard Deviation 2.073	-0.99 Percentage Standard Deviation 2.664	-1.11 Percentage Standard Deviation 1.488
Change From Baseline in Basophil, Eosinophil, Lymphocyte, Monocyte, and Segmented Neutrophil Values at Day 42/Early Withdrawal (EW) Eosinophils, EW, n=2, 2, 0, 0	0.50 Percentage Standard Deviation 0.849	-0.55 Percentage Standard Deviation 2.051	NA Percentage Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Percentage Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Basophil, Eosinophil, Lymphocyte, Monocyte, and Segmented Neutrophil Values at Day 42/Early Withdrawal (EW) Lymphocytes, Day 42, n=50, 47, 53, 11	1.09 Percentage Standard Deviation 6.836	1.54 Percentage Standard Deviation 8.853	-1.32 Percentage Standard Deviation 7.844	-2.48 Percentage Standard Deviation 14.319
Change From Baseline in Basophil, Eosinophil, Lymphocyte, Monocyte, and Segmented Neutrophil Values at Day 42/Early Withdrawal (EW) Lymphocytes, EW, n=2, 2, 0, 0	2.90 Percentage Standard Deviation 10.607	2.00 Percentage Standard Deviation 2.263	NA Percentage Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Percentage Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Basophil, Eosinophil, Lymphocyte, Monocyte, and Segmented Neutrophil Values at Day 42/Early Withdrawal (EW) Monocytes, Day 42, n=50, 47, 53, 11	-0.51 Percentage Standard Deviation 2.074	-0.03 Percentage Standard Deviation 3.333	0.07 Percentage Standard Deviation 2.581	-0.70 Percentage Standard Deviation 1.977
Change From Baseline in Basophil, Eosinophil, Lymphocyte, Monocyte, and Segmented Neutrophil Values at Day 42/Early Withdrawal (EW) Monocytes, EW, n=2, 2, 0, 0	-1.00 Percentage Standard Deviation 0.424	-0.70 Percentage Standard Deviation 3.111	NA Percentage Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Percentage Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Basophil, Eosinophil, Lymphocyte, Monocyte, and Segmented Neutrophil Values at Day 42/Early Withdrawal (EW) Segmented Neutrophils, Day 42, n=50, 47, 53, 11	-1.16 Percentage Standard Deviation 8.291	-1.85 Percentage Standard Deviation 10.279	2.30 Percentage Standard Deviation 9.583	4.37 Percentage Standard Deviation 15.667

SECONDARY outcome

Timeframe: Baseline and Day 42/EW

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of eosinophils, total neutrophils, platelets, and WBC count at Baseline and Day 42/EW. For all laboratory assessments, Baseline is the most recent recorded value at Screening or prior to Day -1/1. Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.

Outcome measures

Measure	Placebo n=58 Participants Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=56 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=56 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=15 Participants Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Change From Baseline in Eosinophil, Total Neutrophil, Platelet, and White Blood Cell (WBC) Count Values at Day 42/EW Eosinophils, Day 42, n=50, 47, 53, 11	0.066 10^9 cells per liter (GI/L) Standard Deviation 0.2282	0.044 10^9 cells per liter (GI/L) Standard Deviation 0.1608	-0.022 10^9 cells per liter (GI/L) Standard Deviation 0.1805	-0.036 10^9 cells per liter (GI/L) Standard Deviation 0.0803
Change From Baseline in Eosinophil, Total Neutrophil, Platelet, and White Blood Cell (WBC) Count Values at Day 42/EW Eosinophils, EW, n=2, 2, 0, 0	0.015 10^9 cells per liter (GI/L) Standard Deviation 0.0071	-0.060 10^9 cells per liter (GI/L) Standard Deviation 0.1697	NA 10^9 cells per liter (GI/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA 10^9 cells per liter (GI/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Eosinophil, Total Neutrophil, Platelet, and White Blood Cell (WBC) Count Values at Day 42/EW Total Neutrophils, Day 42, n=50, 47, 53, 11	0.017 10^9 cells per liter (GI/L) Standard Deviation 1.3317	0.289 10^9 cells per liter (GI/L) Standard Deviation 1.4873	0.704 10^9 cells per liter (GI/L) Standard Deviation 1.2403	1.435 10^9 cells per liter (GI/L) Standard Deviation 2.5515
Change From Baseline in Eosinophil, Total Neutrophil, Platelet, and White Blood Cell (WBC) Count Values at Day 42/EW Total Neutrophils, EW, n=2, 2, 0, 0	-0.420 10^9 cells per liter (GI/L) Standard Deviation 1.7253	-1.165 10^9 cells per liter (GI/L) Standard Deviation 0.9970	NA 10^9 cells per liter (GI/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA 10^9 cells per liter (GI/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Eosinophil, Total Neutrophil, Platelet, and White Blood Cell (WBC) Count Values at Day 42/EW Platelets, Day 42, n=50, 48, 51, 11	-11.1 10^9 cells per liter (GI/L) Standard Deviation 28.72	-8.2 10^9 cells per liter (GI/L) Standard Deviation 31.33	-3.9 10^9 cells per liter (GI/L) Standard Deviation 25.31	16.1 10^9 cells per liter (GI/L) Standard Deviation 16.50
Change From Baseline in Eosinophil, Total Neutrophil, Platelet, and White Blood Cell (WBC) Count Values at Day 42/EW Platelets, EW, n=1, 2, 0, 0	-2.0 10^9 cells per liter (GI/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	-39.5 10^9 cells per liter (GI/L) Standard Deviation 28.99	NA 10^9 cells per liter (GI/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA 10^9 cells per liter (GI/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Eosinophil, Total Neutrophil, Platelet, and White Blood Cell (WBC) Count Values at Day 42/EW WBC Day 42, n=50, 47, 53, 11	0.22 10^9 cells per liter (GI/L) Standard Deviation 1.584	0.71 10^9 cells per liter (GI/L) Standard Deviation 1.787	0.96 10^9 cells per liter (GI/L) Standard Deviation 1.367	1.69 10^9 cells per liter (GI/L) Standard Deviation 2.418
Change From Baseline in Eosinophil, Total Neutrophil, Platelet, and White Blood Cell (WBC) Count Values at Day 42/EW WBC EW, n=2, 2	-0.25 10^9 cells per liter (GI/L) Standard Deviation 1.344	-1.65 10^9 cells per liter (GI/L) Standard Deviation 0.778	NA 10^9 cells per liter (GI/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA 10^9 cells per liter (GI/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.

SECONDARY outcome

Timeframe: Baseline and Day 42/EW

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of hemoglobin at Baseline and Day 42/EW. For all laboratory assessments, Baseline is the most recent recorded value at Screening or prior to Day -1/1. Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.

Outcome measures

Measure	Placebo n=58 Participants Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=56 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=56 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=15 Participants Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Change From Baseline in Hemoglobin Values at Day 42/EW Day 42, n=50, 48, 53, 11	-5.8 Grams per liter (g/L) Standard Deviation 10.28	-6.2 Grams per liter (g/L) Standard Deviation 6.23	-5.7 Grams per liter (g/L) Standard Deviation 6.59	-3.5 Grams per liter (g/L) Standard Deviation 9.27
Change From Baseline in Hemoglobin Values at Day 42/EW EW, n=2, 2, 0, 0	-10.5 Grams per liter (g/L) Standard Deviation 2.12	-3.0 Grams per liter (g/L) Standard Deviation 8.49	NA Grams per liter (g/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Grams per liter (g/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.

SECONDARY outcome

Timeframe: Baseline and Day 42/EW

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of hematocrit at Baseline and Day 42/EW. For all laboratory assessments, Baseline is the most recent recorded value at Screening or prior to Day -1/1. Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.

Outcome measures

Measure	Placebo n=58 Participants Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=56 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=56 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=15 Participants Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Change From Baseline in Hematocrit Values at Day 42/EW Day 42, n=50, 48, 53, 11	-0.0123 Proportion of 1 Standard Deviation 0.02957	-0.0120 Proportion of 1 Standard Deviation 0.02125	-0.0114 Proportion of 1 Standard Deviation 0.02151	-0.0072 Proportion of 1 Standard Deviation 0.02955
Change From Baseline in Hematocrit Values at Day 42/EW EW, n=2, 2, 0, 0	-0.0175 Proportion of 1 Standard Deviation 0.00071	-0.0050 Proportion of 1 Standard Deviation 0.02263	NA Proportion of 1 Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Proportion of 1 Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.

SECONDARY outcome

Timeframe: Baseline and Day 42/EW

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of ALT, ALP, AST, CK, and GGT at Baseline and Day 42/EW. For all laboratory assessments, Baseline is the most recent recorded value at Screening or prior to Day -1/1. Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.

Outcome measures

Measure	Placebo n=58 Participants Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=56 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=56 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=15 Participants Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), and Gamma Glutamyl Transferase (GGT) Values at Day 42/EW ALT, Day 42, n=55, 51, 55, 12	-1.3 International units per liter (IU/L) Standard Deviation 13.05	-2.0 International units per liter (IU/L) Standard Deviation 8.49	-2.2 International units per liter (IU/L) Standard Deviation 10.86	0.8 International units per liter (IU/L) Standard Deviation 3.33
Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), and Gamma Glutamyl Transferase (GGT) Values at Day 42/EW ALT, EW, n=2, 2, 0, 0	-5.0 International units per liter (IU/L) Standard Deviation 8.49	0.5 International units per liter (IU/L) Standard Deviation 2.12	NA International units per liter (IU/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA International units per liter (IU/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), and Gamma Glutamyl Transferase (GGT) Values at Day 42/EW ALP, Day 42, n=55, 51, 55, 12	-6.8 International units per liter (IU/L) Standard Deviation 11.06	-2.1 International units per liter (IU/L) Standard Deviation 13.96	-2.6 International units per liter (IU/L) Standard Deviation 8.33	-4.9 International units per liter (IU/L) Standard Deviation 9.86
Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), and Gamma Glutamyl Transferase (GGT) Values at Day 42/EW ALP, EW, n=2, 2, 0, 0	1.5 International units per liter (IU/L) Standard Deviation 9.19	-1.0 International units per liter (IU/L) Standard Deviation 1.41	NA International units per liter (IU/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA International units per liter (IU/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), and Gamma Glutamyl Transferase (GGT) Values at Day 42/EW AST, Day 42, n=54, 50, 51, 12	-0.1 International units per liter (IU/L) Standard Deviation 12.42	-1.4 International units per liter (IU/L) Standard Deviation 6.82	-0.6 International units per liter (IU/L) Standard Deviation 6.91	-1.8 International units per liter (IU/L) Standard Deviation 5.67
Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), and Gamma Glutamyl Transferase (GGT) Values at Day 42/EW AST, EW, n=2, 2, 0, 0	0.5 International units per liter (IU/L) Standard Deviation 0.71	0.0 International units per liter (IU/L) Standard Deviation 1.41	NA International units per liter (IU/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA International units per liter (IU/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), and Gamma Glutamyl Transferase (GGT) Values at Day 42/EW CK, Day 42, n=55, 51, 55, 12	-42.3 International units per liter (IU/L) Standard Deviation 342.74	-18.5 International units per liter (IU/L) Standard Deviation 289.98	5.5 International units per liter (IU/L) Standard Deviation 67.57	-17.3 International units per liter (IU/L) Standard Deviation 95.02
Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), and Gamma Glutamyl Transferase (GGT) Values at Day 42/EW CK, EW, n=2, 2, 0, 0	15.0 International units per liter (IU/L) Standard Deviation 21.21	33.0 International units per liter (IU/L) Standard Deviation 73.54	NA International units per liter (IU/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA International units per liter (IU/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), and Gamma Glutamyl Transferase (GGT) Values at Day 42/EW GGT, Day 42, n=55, 51, 55, 12	-3.3 International units per liter (IU/L) Standard Deviation 10.65	-2.5 International units per liter (IU/L) Standard Deviation 6.94	2.2 International units per liter (IU/L) Standard Deviation 17.24	3.1 International units per liter (IU/L) Standard Deviation 7.32
Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), and Gamma Glutamyl Transferase (GGT) Values at Day 42/EW GGT, EW, n=2, 2, 0, 0	-2.5 International units per liter (IU/L) Standard Deviation 6.36	-0.5 International units per liter (IU/L) Standard Deviation 0.71	NA International units per liter (IU/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA International units per liter (IU/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.

SECONDARY outcome

Timeframe: Baseline and Day 42/EW

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of albumin and total protein at Baseline and Day 42/EW. For all laboratory assessments, Baseline is the most recent recorded value at Screening or prior to Day -1/1. Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.

Outcome measures

Measure	Placebo n=58 Participants Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=56 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=56 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=15 Participants Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Change From Baseline in Albumin and Total Protein Values at Day 42/EW Albumin, Day 42, n=55, 51, 55, 12	-2.7 Grams per liter Standard Deviation 3.29	-1.5 Grams per liter Standard Deviation 3.02	-1.3 Grams per liter Standard Deviation 3.11	-0.3 Grams per liter Standard Deviation 2.81
Change From Baseline in Albumin and Total Protein Values at Day 42/EW Albumin, EW, n=2, 2, 0, 0	-1.5 Grams per liter Standard Deviation 3.54	0.5 Grams per liter Standard Deviation 2.12	NA Grams per liter Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Grams per liter Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Albumin and Total Protein Values at Day 42/EW Total Protein, Day 42, n=55, 51, 55, 12	-4.1 Grams per liter Standard Deviation 5.06	-1.9 Grams per liter Standard Deviation 4.39	-1.8 Grams per liter Standard Deviation 4.65	-0.8 Grams per liter Standard Deviation 4.18
Change From Baseline in Albumin and Total Protein Values at Day 42/EW Total Protein, EW, n=2, 2, 0, 0	-0.5 Grams per liter Standard Deviation 3.54	0.0 Grams per liter Standard Deviation 0.00	NA Grams per liter Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Grams per liter Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.

SECONDARY outcome

Timeframe: Baseline and Day 42/EW

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of direct bilirubin, indirect bilirubin, total bilirubin, and creatinine at Baseline and Day 42/EW. For all laboratory assessments, Baseline is the most recent recorded value at Screening or prior to Day -1/1. Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.

Outcome measures

Measure	Placebo n=58 Participants Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=56 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=56 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=15 Participants Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine Values at Day 42/EW Direct Bilirubin, Day 42, n=55, 51, 55, 12	-0.6 Micromoles per liter (µmol/L) Standard Deviation 1.12	-0.6 Micromoles per liter (µmol/L) Standard Deviation 1.02	-0.5 Micromoles per liter (µmol/L) Standard Deviation 1.10	0.3 Micromoles per liter (µmol/L) Standard Deviation 0.75
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine Values at Day 42/EW Direct Bilirubin, EW, n=2, 2, 0, 0	-1.0 Micromoles per liter (µmol/L) Standard Deviation 0.00	0.0 Micromoles per liter (µmol/L) Standard Deviation 0.00	NA Micromoles per liter (µmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Micromoles per liter (µmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine Values at Day 42/EW Indirect Bilirubin, Day 42, n=55, 51, 55, 12	-2.0 Micromoles per liter (µmol/L) Standard Deviation 4.89	-2.5 Micromoles per liter (µmol/L) Standard Deviation 3.20	-1.4 Micromoles per liter (µmol/L) Standard Deviation 4.72	-1.0 Micromoles per liter (µmol/L) Standard Deviation 2.76
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine Values at Day 42/EW Indirect Bilirubin, EW, n=2, 2, 0, 0	-1.5 Micromoles per liter (µmol/L) Standard Deviation 2.12	-2.0 Micromoles per liter (µmol/L) Standard Deviation 0.00	NA Micromoles per liter (µmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Micromoles per liter (µmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine Values at Day 42/EW Total Bilirubin, Day 42, n=55, 51, 55, 12	-2.5 Micromoles per liter (µmol/L) Standard Deviation 5.66	-3.2 Micromoles per liter (µmol/L) Standard Deviation 3.72	-1.8 Micromoles per liter (µmol/L) Standard Deviation 5.67	-0.8 Micromoles per liter (µmol/L) Standard Deviation 2.86
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine Values at Day 42/EW Total Bilirubin, EW, n=2, 2, 0, 0	-2.5 Micromoles per liter (µmol/L) Standard Deviation 2.12	-2.0 Micromoles per liter (µmol/L) Standard Deviation 0.00	NA Micromoles per liter (µmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Micromoles per liter (µmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine Values at Day 42/EW Creatinine, Day 42, n=55, 51, 55, 12	-0.41 Micromoles per liter (µmol/L) Standard Deviation 8.688	0.35 Micromoles per liter (µmol/L) Standard Deviation 8.088	0.04 Micromoles per liter (µmol/L) Standard Deviation 8.052	4.61 Micromoles per liter (µmol/L) Standard Deviation 9.585
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine Values at Day 42/EW Creatinine, EW, n=2, 2, 0, 0	0.00 Micromoles per liter (µmol/L) Standard Deviation 13.435	0.95 Micromoles per liter (µmol/L) Standard Deviation 6.435	NA Micromoles per liter (µmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Micromoles per liter (µmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.

SECONDARY outcome

Timeframe: Baseline and Day 42/EW

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of chloride, carbon dioxide (CO2) content/bicarbonate, glucose, potassium, sodium, and urea/blood urea nitrogen (BUN) at Baseline and Day 42/EW. For all laboratory assessments, Baseline is the most recent recorded value at Screening or prior to Day -1/1. Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.

Outcome measures

Measure	Placebo n=58 Participants Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=56 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=56 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=15 Participants Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Change From Baseline in Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 42/EW Chloride, Day 42, n=55, 51, 55, 12	1.2 Millimoles per liter (mmol/L) Standard Deviation 2.54	0.9 Millimoles per liter (mmol/L) Standard Deviation 2.76	0.7 Millimoles per liter (mmol/L) Standard Deviation 3.06	-1.0 Millimoles per liter (mmol/L) Standard Deviation 2.41
Change From Baseline in Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 42/EW Chloride, EW, n=2, 2, 0, 0	2.0 Millimoles per liter (mmol/L) Standard Deviation 1.41	-0.5 Millimoles per liter (mmol/L) Standard Deviation 0.71	NA Millimoles per liter (mmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Millimoles per liter (mmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 42/EW CO2 content/bicarbonate, Day 42, n=54, 50, 51, 12	-1.0 Millimoles per liter (mmol/L) Standard Deviation 2.86	-2.0 Millimoles per liter (mmol/L) Standard Deviation 2.98	-1.5 Millimoles per liter (mmol/L) Standard Deviation 2.35	-0.1 Millimoles per liter (mmol/L) Standard Deviation 3.12
Change From Baseline in Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 42/EW CO2 content/bicarbonate, EW, n=2, 2, 0, 0	-3.5 Millimoles per liter (mmol/L) Standard Deviation 2.12	0.0 Millimoles per liter (mmol/L) Standard Deviation 1.41	NA Millimoles per liter (mmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Millimoles per liter (mmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 42/EW Glucose, Day 42, n=55, 51, 55, 12	0.11 Millimoles per liter (mmol/L) Standard Deviation 1.117	0.23 Millimoles per liter (mmol/L) Standard Deviation 1.037	-0.03 Millimoles per liter (mmol/L) Standard Deviation 0.573	0.40 Millimoles per liter (mmol/L) Standard Deviation 1.397
Change From Baseline in Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 42/EW Glucose, EW, n=2, 2, 0, 0	1.00 Millimoles per liter (mmol/L) Standard Deviation 0.283	0.40 Millimoles per liter (mmol/L) Standard Deviation 0.849	NA Millimoles per liter (mmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Millimoles per liter (mmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 42/EW Potassium, Day 42, n=54, 50, 51, 12	-0.10 Millimoles per liter (mmol/L) Standard Deviation 0.385	-0.11 Millimoles per liter (mmol/L) Standard Deviation 0.405	-0.16 Millimoles per liter (mmol/L) Standard Deviation 0.379	0.03 Millimoles per liter (mmol/L) Standard Deviation 0.599
Change From Baseline in Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 42/EW Potassium, EW, n=2, 2, 0, 0	-0.20 Millimoles per liter (mmol/L) Standard Deviation 0.283	-0.65 Millimoles per liter (mmol/L) Standard Deviation 0.071	NA Millimoles per liter (mmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Millimoles per liter (mmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 42/EW Sodium, Day 42, n=55, 51, 55, 12	0.0 Millimoles per liter (mmol/L) Standard Deviation 2.03	-0.1 Millimoles per liter (mmol/L) Standard Deviation 1.98	-0.1 Millimoles per liter (mmol/L) Standard Deviation 3.01	-0.2 Millimoles per liter (mmol/L) Standard Deviation 1.85
Change From Baseline in Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 42/EW Sodium, EW, n=2, 2, 0, 0	1.5 Millimoles per liter (mmol/L) Standard Deviation 3.54	-3.5 Millimoles per liter (mmol/L) Standard Deviation 0.71	NA Millimoles per liter (mmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Millimoles per liter (mmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.
Change From Baseline in Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 42/EW Urea/BUN, Day 42, n=55, 51, 55, 12	-0.14 Millimoles per liter (mmol/L) Standard Deviation 1.432	0.48 Millimoles per liter (mmol/L) Standard Deviation 1.441	-0.00 Millimoles per liter (mmol/L) Standard Deviation 1.236	0.94 Millimoles per liter (mmol/L) Standard Deviation 1.331
Change From Baseline in Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 42/EW Urea/BUN, EW, n=2, 2, 0, 0	1.30 Millimoles per liter (mmol/L) Standard Deviation 0.283	-0.85 Millimoles per liter (mmol/L) Standard Deviation 0.919	NA Millimoles per liter (mmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.	NA Millimoles per liter (mmol/L) Standard Deviation NA Data are not available (missing) for some participants who withdrew from the study early.

SECONDARY outcome

Timeframe: Days 14, 28, 42, and EW

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

SBP and DBP were measured at Baseline and at Days 14, 28, 42, and EW. Change from Baseline was calculated as the Day 42/EW value minus the Baseline value. Scheduled, unscheduled, and early withdrawal visits were used for the maximum post-Baseline assessment.

Outcome measures

Measure	Placebo n=58 Participants Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=56 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=56 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=15 Participants Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Days 14, 28, 42, and Maximum Post-Baseline SBP, Day 14, n=58, 55, 56, 14	-0.5 Millimeters of mercury (mmHg) Standard Deviation 11.68	-1.9 Millimeters of mercury (mmHg) Standard Deviation 10.88	-1.3 Millimeters of mercury (mmHg) Standard Deviation 10.53	-1.0 Millimeters of mercury (mmHg) Standard Deviation 13.33
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Days 14, 28, 42, and Maximum Post-Baseline SBP, Day 28, n=57, 55, 56, 14	-0.9 Millimeters of mercury (mmHg) Standard Deviation 9.55	-0.7 Millimeters of mercury (mmHg) Standard Deviation 10.70	-2.3 Millimeters of mercury (mmHg) Standard Deviation 11.66	-3.9 Millimeters of mercury (mmHg) Standard Deviation 13.35
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Days 14, 28, 42, and Maximum Post-Baseline SBP, Day 42, n=55, 54, 56, 13	2.3 Millimeters of mercury (mmHg) Standard Deviation 11.96	-0.4 Millimeters of mercury (mmHg) Standard Deviation 12.72	-1.8 Millimeters of mercury (mmHg) Standard Deviation 11.20	1.5 Millimeters of mercury (mmHg) Standard Deviation 8.26
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Days 14, 28, 42, and Maximum Post-Baseline SBP, maximum post-Baseline, n=58, 56, 56, 15	6.2 Millimeters of mercury (mmHg) Standard Deviation 11.44	5.0 Millimeters of mercury (mmHg) Standard Deviation 10.88	3.9 Millimeters of mercury (mmHg) Standard Deviation 10.80	4.9 Millimeters of mercury (mmHg) Standard Deviation 8.61
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Days 14, 28, 42, and Maximum Post-Baseline DBP, Day 14, n=58, 55, 56, 14	0.0 Millimeters of mercury (mmHg) Standard Deviation 7.92	-1.1 Millimeters of mercury (mmHg) Standard Deviation 8.26	-0.6 Millimeters of mercury (mmHg) Standard Deviation 9.08	0.1 Millimeters of mercury (mmHg) Standard Deviation 8.55
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Days 14, 28, 42, and Maximum Post-Baseline DBP, Day 28, n=57, 55, 56, 14	1.8 Millimeters of mercury (mmHg) Standard Deviation 8.38	-0.6 Millimeters of mercury (mmHg) Standard Deviation 7.63	0.1 Millimeters of mercury (mmHg) Standard Deviation 9.97	-0.4 Millimeters of mercury (mmHg) Standard Deviation 8.11
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Days 14, 28, 42, and Maximum Post-Baseline DBP, Day 42, n=55, 54, 56, 13	1.2 Millimeters of mercury (mmHg) Standard Deviation 8.77	-1.2 Millimeters of mercury (mmHg) Standard Deviation 9.13	0.3 Millimeters of mercury (mmHg) Standard Deviation 8.74	1.2 Millimeters of mercury (mmHg) Standard Deviation 8.69
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Days 14, 28, 42, and Maximum Post-Baseline DBP, maximum post-Baseline, n=58, 56, 56, 15	-3.3 Millimeters of mercury (mmHg) Standard Deviation 7.04	-5.2 Millimeters of mercury (mmHg) Standard Deviation 7.76	-5.4 Millimeters of mercury (mmHg) Standard Deviation 9.00	-4.9 Millimeters of mercury (mmHg) Standard Deviation 7.97

SECONDARY outcome

Timeframe: Days 14, 28, 42, and EW

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

Heart rate was measured at Baseline and at Days 14, 28, 42, and EW. Change from Baseline was calculated as the Day 42/EW value minus the Baseline value. Scheduled, unscheduled, and early withdrawal visits were used for the maximum post-Baseline assessment.

Outcome measures

Measure	Placebo n=58 Participants Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=56 Participants Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=56 Participants Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=15 Participants Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Change From Baseline in Pulse Rate at Days 14, 28, 42, and Maximum Post-Baseline Day 14, n=58, 55, 56, 14	1.5 Beats per minute Standard Deviation 13.05	1.7 Beats per minute Standard Deviation 10.70	0.0 Beats per minute Standard Deviation 8.72	-1.8 Beats per minute Standard Deviation 7.92
Change From Baseline in Pulse Rate at Days 14, 28, 42, and Maximum Post-Baseline Day 28, n=57, 55, 56, 14	2.9 Beats per minute Standard Deviation 13.45	-0.9 Beats per minute Standard Deviation 9.32	-1.9 Beats per minute Standard Deviation 12.05	-2.7 Beats per minute Standard Deviation 11.89
Change From Baseline in Pulse Rate at Days 14, 28, 42, and Maximum Post-Baseline Day 42, n=55, 54, 56, 13	-0.1 Beats per minute Standard Deviation 12.65	-0.9 Beats per minute Standard Deviation 11.43	0.9 Beats per minute Standard Deviation 8.96	-2.3 Beats per minute Standard Deviation 9.10
Change From Baseline in Pulse Rate at Days 14, 28, 42, and Maximum Post-Baseline Maximum post-Baseline, n=58, 56, 56, 15	8.0 Beats per minute Standard Deviation 12.47	6.0 Beats per minute Standard Deviation 9.86	5.5 Beats per minute Standard Deviation 8.64	2.9 Beats per minute Standard Deviation 9.13

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

FF/VI 100/25 µg PM

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

FF/VI 200/25 µg PM

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Prednisolone 10 mg AM

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=58 participants at risk Participants received placebo via a Dry Powder Inhaler (DPI) for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening for 6 weeks and to take one placebo capsule each morning on the last 7 days of treatment.	FF/VI 100/25 µg PM n=56 participants at risk Participants received Fluticasone Furoate/Vilanterol (FF/VI) 100/25 micrograms (µg) via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	FF/VI 200/25 µg PM n=56 participants at risk Participants received FF/VI 200/25 µg via a DPI for 6 weeks, plus a placebo capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one placebo capsule each morning (AM) on the last 7 days of treatment.	Prednisolone 10 mg AM n=15 participants at risk Participants received placebo via a DPI for 6 weeks, plus a prednisolone 10 milligram (mg) capsule on the last 7 days of treatment. Participants were instructed to self-administer one inhalation of placebo from the DPI once daily at approximately the same time each evening (PM) for 6 weeks and to take one Prednisolone capsule each morning (AM) on the last 7 days of treatment.
Nervous system disorders Headache	8.6% 5/58	26.8% 15/56	16.1% 9/56	13.3% 2/15
Nervous system disorders Sinus headache	0.00% 0/58	1.8% 1/56	3.6% 2/56	0.00% 0/15
Nervous system disorders Dizziness	0.00% 0/58	0.00% 0/56	0.00% 0/56	6.7% 1/15
Nervous system disorders Facial palsy	0.00% 0/58	0.00% 0/56	0.00% 0/56	6.7% 1/15
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.4% 2/58	1.8% 1/56	0.00% 0/56	0.00% 0/15
Respiratory, thoracic and mediastinal disorders Cough	3.4% 2/58	0.00% 0/56	0.00% 0/56	0.00% 0/15
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/58	3.6% 2/56	0.00% 0/56	0.00% 0/15
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/58	0.00% 0/56	0.00% 0/56	6.7% 1/15
Infections and infestations Nasopharyngitis	1.7% 1/58	3.6% 2/56	1.8% 1/56	0.00% 0/15
Infections and infestations Sinusitis	0.00% 0/58	3.6% 2/56	0.00% 0/56	0.00% 0/15
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/58	1.8% 1/56	3.6% 2/56	6.7% 1/15
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/58	3.6% 2/56	0.00% 0/56	0.00% 0/15
Gastrointestinal disorders Nausea	1.7% 1/58	0.00% 0/56	0.00% 0/56	6.7% 1/15
Vascular disorders Hypotension	0.00% 0/58	0.00% 0/56	0.00% 0/56	6.7% 1/15
Vascular disorders Varicose vein	0.00% 0/58	0.00% 0/56	0.00% 0/56	6.7% 1/15
General disorders Fatigue	0.00% 0/58	0.00% 0/56	0.00% 0/56	6.7% 1/15
Psychiatric disorders Insomnia	0.00% 0/58	0.00% 0/56	0.00% 0/56	6.7% 1/15

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