Trial Outcomes & Findings for Phase IV Study in Asthma Subjects for Dry Powder Inhaler (DPI) Versus (vs) Metered Dose Inhaler (MDI) Correct Use (NCT NCT02794480)

Last Updated: 2019-07-02

Results Overview

A checklist for correct use of each inhaler was developed based on the steps identified in the package insert. Baseline assessment was conducted when the par were dispensed the inhaler and were guided by a trained healthcare provider (HCP) to demonstrate correct use of the assigned inhaler. A second assessment was conducted after each 28 day dosing period without instruction by HCP. The Correct Use Check list was completed by HCP at each visit. Percentage of par with zero errors in inhaler use at Day 28, was analyzed using a Mainland-Gart test for each ELLIPTA versus MDI comparison separately (Sub-study 1: ELLIPTA vs GSK MDI and Sub-study 2: ELLIPTA vs AZ MDI). For each ELLIPTA vs MDI analyses, only par who made no error in any of the inhalers and at least one error on the other inhaler (discordant cases) were included in the analysis. NA indicates that par did not receive the inhaler in that particular sub-study.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

324 participants

Primary outcome timeframe

Up to Day 56

Results posted on

2019-07-02

Participant Flow

This is a randomized, multi-center, open-label, cross-over study comparing Placebo ELLIPTA Dry Power Inhaler (DPI) with either Placebo GlaxoSmithKline (GSK) Metered Dose Inhaler (MDI) or Placebo Astra Zeneca (AZ) MDI to assess correct inhaler use. A total of 20 sites in the United States (US) participated in the study.

A total of 329 participants (par) were screened out of which 324 were randomized to sub-study 1 and sub-study 2 in a ratio of 1:1. Each par received at least one-dose of placebo from at least one study inhaler. These par comprised the intent to treat (ITT) population. Par were randomized on the same day as screening.

Participant milestones

Participant milestones
Measure	Sub-Study 1 (Seq 3: Ellipta/GSK MDI) Par were randomized to treatment sequence 3 or 4. In treatment sequence 3, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo GSK MDI at Visit 2 for treatment period 2. In treatment sequence 4, the par were dispensed Placebo GSK MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. GSK MDI contained propellant (1,1,1,2-Tetrafluoroethane). ELLIPTA DPI was taken as one inhalation, once daily and GSK MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.	Sub-Study 1 (Seq 4: GSK MDI/Ellipta) Par were randomized to treatment sequence 3 or 4. In treatment sequence 3, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo GSK MDI at Visit 2 for treatment period 2. In treatment sequence 4, the par were dispensed Placebo GSK MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. GSK MDI contained propellant (1,1,1,2-Tetrafluoroethane). ELLIPTA DPI was taken as one inhalation, once daily and GSK MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.	Sub-Study 2 (Seq 1: Ellipta/AZ MDI) Par were randomized to treatment sequence 1 or 2. In treatment sequence 1, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo AZ MDI at Visit 2 for treatment period 2. In treatment sequence 2, the par were dispensed Placebo AZ MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. AZ MDI was a placebo inhaler containing liquid aerosol. ELLIPTA DPI was taken as one inhalation, once daily and AZ MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.	Sub-Study 2 (Seq 2: AZ MDI/Ellipta) Par were randomized to treatment sequence 1 or 2. In treatment sequence 1, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo AZ MDI at Visit 2 for treatment period 2. In treatment sequence 2, the par were dispensed Placebo AZ MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. AZ MDI was a placebo inhaler containing liquid aerosol. ELLIPTA DPI was taken as one inhalation, once daily and AZ MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.
Period 1: Treatment Period 1 (28 Days) STARTED	80	82	81	81
Period 1: Treatment Period 1 (28 Days) COMPLETED	80	80	79	78
Period 1: Treatment Period 1 (28 Days) NOT COMPLETED	0	2	2	3
Period 2: Treatment Period 2 (28 Days) STARTED	80	80	79	78
Period 2: Treatment Period 2 (28 Days) COMPLETED	79	80	79	77
Period 2: Treatment Period 2 (28 Days) NOT COMPLETED	1	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Sub-Study 1 (Seq 3: Ellipta/GSK MDI) Par were randomized to treatment sequence 3 or 4. In treatment sequence 3, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo GSK MDI at Visit 2 for treatment period 2. In treatment sequence 4, the par were dispensed Placebo GSK MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. GSK MDI contained propellant (1,1,1,2-Tetrafluoroethane). ELLIPTA DPI was taken as one inhalation, once daily and GSK MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.	Sub-Study 1 (Seq 4: GSK MDI/Ellipta) Par were randomized to treatment sequence 3 or 4. In treatment sequence 3, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo GSK MDI at Visit 2 for treatment period 2. In treatment sequence 4, the par were dispensed Placebo GSK MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. GSK MDI contained propellant (1,1,1,2-Tetrafluoroethane). ELLIPTA DPI was taken as one inhalation, once daily and GSK MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.	Sub-Study 2 (Seq 1: Ellipta/AZ MDI) Par were randomized to treatment sequence 1 or 2. In treatment sequence 1, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo AZ MDI at Visit 2 for treatment period 2. In treatment sequence 2, the par were dispensed Placebo AZ MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. AZ MDI was a placebo inhaler containing liquid aerosol. ELLIPTA DPI was taken as one inhalation, once daily and AZ MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.	Sub-Study 2 (Seq 2: AZ MDI/Ellipta) Par were randomized to treatment sequence 1 or 2. In treatment sequence 1, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo AZ MDI at Visit 2 for treatment period 2. In treatment sequence 2, the par were dispensed Placebo AZ MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. AZ MDI was a placebo inhaler containing liquid aerosol. ELLIPTA DPI was taken as one inhalation, once daily and AZ MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.
Period 1: Treatment Period 1 (28 Days) Adverse Event	0	0	1	0
Period 1: Treatment Period 1 (28 Days) Protocol Violation	0	0	1	0
Period 1: Treatment Period 1 (28 Days) Lost to Follow-up	0	0	0	2
Period 1: Treatment Period 1 (28 Days) Withdrawal by Subject	0	2	0	1
Period 2: Treatment Period 2 (28 Days) Withdrawal by Subject	1	0	0	1

Baseline Characteristics

Phase IV Study in Asthma Subjects for Dry Powder Inhaler (DPI) Versus (vs) Metered Dose Inhaler (MDI) Correct Use

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sub-Study 1 (Seq 3: Ellipta/GSK MDI; Seq 4: GSK MDI/Ellipta) n=157 Participants Par were randomized to treatment sequence 3 or 4. In treatment sequence 3, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo GSK MDI at Visit 2 for treatment period 2. In treatment sequence 4, the par were dispensed Placebo GSK MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. GSK MDI contained propellant (1,1,1,2-Tetrafluoroethane). ELLIPTA DPI was taken as one inhalation, once daily and GSK MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.	Sub-Study 2 (Seq 1: Ellipta/AZ MDI; Seq 2: AZ MDI/Ellipta) n=153 Participants Par were randomized to treatment sequence 1 or 2. In treatment sequence 1, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo AZ MDI at Visit 2 for treatment period 2. In treatment sequence 2, the par were dispensed Placebo AZ MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. AZ MDI was a placebo inhaler containing liquid aerosol. ELLIPTA DPI was taken as one inhalation, once daily and AZ MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.	Total n=310 Participants Total of all reporting groups
Age, Continuous	51.4 Years STANDARD_DEVIATION 15.87 • n=5 Participants	50.9 Years STANDARD_DEVIATION 15.08 • n=7 Participants	51.1 Years STANDARD_DEVIATION 15.46 • n=5 Participants
Sex: Female, Male Female	108 Participants n=5 Participants	108 Participants n=7 Participants	216 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants	45 Participants n=7 Participants	94 Participants n=5 Participants
Race/Ethnicity, Customized race customized · AMERICAN INDIAN OR ALASKA NATIVE	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized race customized · ASIAN - CENTRAL/SOUTH ASIAN HERITAGE	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized race customized · ASIAN - EAST ASIAN HERITAGE	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized race customized · ASIAN - JAPANESE HERITAGE	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized race customized · ASIAN - SOUTH EAST ASIAN HERITAGE	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized race customized · BLACK OR AFRICAN AMERICAN	36 Participants n=5 Participants	33 Participants n=7 Participants	69 Participants n=5 Participants
Race/Ethnicity, Customized race customized · WHITE - ARABIC/NORTH AFRICAN HERITAGE	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized race customized · WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE	115 Participants n=5 Participants	113 Participants n=7 Participants	228 Participants n=5 Participants
Race/Ethnicity, Customized race customized · MULTIPLE	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Day 56

Population: Modified ITT Population (MITT) comprises of all par in the ITT Population who provided Day 28 inhaler use data for both of their randomized inhalers.

Outcome measures

Outcome measures
Measure	Sub-Study 1 n=24 Participants Par were randomized to treatment sequence 3 or 4. In treatment sequence 3, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo GSK MDI at Visit 2 for treatment period 2. In treatment sequence 4, the par were dispensed Placebo GSK MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. GSK MDI contained propellant (1,1,1,2-Tetrafluoroethane). ELLIPTA DPI was taken as one inhalation, once daily and GSK MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.	Sub-Study 2 n=15 Participants Par were randomized to treatment sequence 1 or 2. In treatment sequence 1, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo AZ MDI at Visit 2 for treatment period 2. In treatment sequence 2, the par were dispensed Placebo AZ MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. AZ MDI was a placebo inhaler containing liquid aerosol. ELLIPTA DPI was taken as one inhalation, once daily and AZ MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.
Percentage of Participants With Zero Errors in ELLIPTA DPI Versus GSK MDI and AZ MDI After 28 Days of Use in Each Treatment Phase ELLIPTA	87 Percentage of Participants	87 Percentage of Participants
Percentage of Participants With Zero Errors in ELLIPTA DPI Versus GSK MDI and AZ MDI After 28 Days of Use in Each Treatment Phase GSK MDI	13 Percentage of Participants	NA Percentage of Participants NA indicates that the par did not receive the inhaler in that particular sub-study.
Percentage of Participants With Zero Errors in ELLIPTA DPI Versus GSK MDI and AZ MDI After 28 Days of Use in Each Treatment Phase AZ MDI	NA Percentage of Participants NA indicates that the par did not receive the inhaler in that particular sub-study.	13 Percentage of Participants

SECONDARY outcome

Timeframe: Up to Day 56

Population: MITT Population

The occurrence of each type of error while using ELLIPTA inhaler was evaluated based on the information collected in the Correct Use Checklists. The number of errors for each type of inhaler was assessed at Visit 2 and Visit 3. The par were counted more than once depending on the reasons for incorrect use. Only par who made at least one error was included in the summary (represented by the number of Participants).

Outcome measures

Outcome measures
Measure	Sub-Study 1 n=7 Participants Par were randomized to treatment sequence 3 or 4. In treatment sequence 3, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo GSK MDI at Visit 2 for treatment period 2. In treatment sequence 4, the par were dispensed Placebo GSK MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. GSK MDI contained propellant (1,1,1,2-Tetrafluoroethane). ELLIPTA DPI was taken as one inhalation, once daily and GSK MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.	Sub-Study 2 n=3 Participants Par were randomized to treatment sequence 1 or 2. In treatment sequence 1, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo AZ MDI at Visit 2 for treatment period 2. In treatment sequence 2, the par were dispensed Placebo AZ MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. AZ MDI was a placebo inhaler containing liquid aerosol. ELLIPTA DPI was taken as one inhalation, once daily and AZ MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.
Frequency of Errors by Type for ELLIPTA After 28 Days of Use in Each Treatment Phase Par did shake the inhaler (ir)	3 Participants	0 Participants
Frequency of Errors by Type for ELLIPTA After 28 Days of Use in Each Treatment Phase Par didn't exhale when ir was held away from mouth	2 Participants	2 Participants
Frequency of Errors by Type for ELLIPTA After 28 Days of Use in Each Treatment Phase Par breathed into the mouthpiece (mp)	2 Participants	0 Participants
Frequency of Errors by Type for ELLIPTA After 28 Days of Use in Each Treatment Phase Mp was not placed with lips closed around it	1 Participants	0 Participants
Frequency of Errors by Type for ELLIPTA After 28 Days of Use in Each Treatment Phase Par did not take one long steady deep breath	1 Participants	1 Participants
Frequency of Errors by Type for ELLIPTA After 28 Days of Use in Each Treatment Phase Par didn't remove ir from mouth and hold breath	1 Participants	1 Participants
Frequency of Errors by Type for ELLIPTA After 28 Days of Use in Each Treatment Phase Par did not breathe out slowly and gently	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to Day 56

Population: MITT Population

The occurrence of each type of error while using GSK MDI in Sub-Study 1 and AZ MDI in Sub-Study 2 was evaluated based on the information collected in the Correct Use Checklists. The number of errors for each type of inhaler was assessed at Visit 2 and Visit 3. The par were counted more than once depending on the reasons for incorrect use. The number of errors is reported as NA for the type of error which was not applicable to the particular inhaler type. Only par who made at least one error are included in the summary (represented by the number of Participants).

Outcome measures

Outcome measures
Measure	Sub-Study 1 n=25 Participants Par were randomized to treatment sequence 3 or 4. In treatment sequence 3, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo GSK MDI at Visit 2 for treatment period 2. In treatment sequence 4, the par were dispensed Placebo GSK MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. GSK MDI contained propellant (1,1,1,2-Tetrafluoroethane). ELLIPTA DPI was taken as one inhalation, once daily and GSK MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.	Sub-Study 2 n=14 Participants Par were randomized to treatment sequence 1 or 2. In treatment sequence 1, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo AZ MDI at Visit 2 for treatment period 2. In treatment sequence 2, the par were dispensed Placebo AZ MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. AZ MDI was a placebo inhaler containing liquid aerosol. ELLIPTA DPI was taken as one inhalation, once daily and AZ MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.
Frequency of Errors by Type for MDI After 28 Days of Use in Each Treatment Phase Par did not shake the inhaler	5 Participants	5 Participants
Frequency of Errors by Type for MDI After 28 Days of Use in Each Treatment Phase Par did not check the mp for foreign objects	14 Participants	9 Participants
Frequency of Errors by Type for MDI After 28 Days of Use in Each Treatment Phase Par did not hold the inhaler with the mp down	1 Participants	NA Participants The number of errors are reported as NA for the type of error which was not applicable to the particular inhaler type.
Frequency of Errors by Type for MDI After 28 Days of Use in Each Treatment Phase Par did not breathe out fully	5 Participants	0 Participants
Frequency of Errors by Type for MDI After 28 Days of Use in Each Treatment Phase Mp was not placed with lips closed around it	2 Participants	0 Participants
Frequency of Errors by Type for MDI After 28 Days of Use in Each Treatment Phase Par did not press top of canister all way down	2 Participants	2 Participants
Frequency of Errors by Type for MDI After 28 Days of Use in Each Treatment Phase Ability to release actuation was not demonstrated	4 Participants	2 Participants
Frequency of Errors by Type for MDI After 28 Days of Use in Each Treatment Phase Par did not take finger off the canister	3 Participants	2 Participants
Frequency of Errors by Type for MDI After 28 Days of Use in Each Treatment Phase Par did not remove inhaler from mouth & closed it	2 Participants	NA Participants The number of errors are reported as NA for the type of error which was not applicable to the particular inhaler type.
Frequency of Errors by Type for MDI After 28 Days of Use in Each Treatment Phase Par didn't hold breath for 10 s & exhale slowly	3 Participants	2 Participants
Frequency of Errors by Type for MDI After 28 Days of Use in Each Treatment Phase Par did not snap the cap back firmly into place	2 Participants	0 Participants
Frequency of Errors by Type for MDI After 28 Days of Use in Each Treatment Phase Inhaler was not kept upright & removed from mouth	NA Participants The number of errors are reported as NA for the type of error which was not applicable to the particular inhaler type.	2 Participants
Frequency of Errors by Type for MDI After 28 Days of Use in Each Treatment Phase Par did not close the inhaler completely	NA Participants The number of errors are reported as NA for the type of error which was not applicable to the particular inhaler type.	1 Participants

SECONDARY outcome

Timeframe: Up to Day 56

Population: MITT Population

The number of errors per par for each inhaler (ELLIPTA and GSK MDI or AZ MDI) was evaluated based on the information collected in the Correct Use Checklists. The number of errors per par was summarised as continuous data by inhaler for each of the ELLIPTA versus MDI comparisons. NA indicates that the par did not receive the inhaler in that particular sub-study.

Outcome measures

Outcome measures
Measure	Sub-Study 1 n=157 Participants Par were randomized to treatment sequence 3 or 4. In treatment sequence 3, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo GSK MDI at Visit 2 for treatment period 2. In treatment sequence 4, the par were dispensed Placebo GSK MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. GSK MDI contained propellant (1,1,1,2-Tetrafluoroethane). ELLIPTA DPI was taken as one inhalation, once daily and GSK MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.	Sub-Study 2 n=153 Participants Par were randomized to treatment sequence 1 or 2. In treatment sequence 1, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo AZ MDI at Visit 2 for treatment period 2. In treatment sequence 2, the par were dispensed Placebo AZ MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. AZ MDI was a placebo inhaler containing liquid aerosol. ELLIPTA DPI was taken as one inhalation, once daily and AZ MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.
Number of Errors Per Participant for Each Inhaler After 28 Days of Use (All Evaluable Par) ELLIPTA	0.07 Errors Standard Deviation 0.393	0.04 Errors Standard Deviation 0.299
Number of Errors Per Participant for Each Inhaler After 28 Days of Use (All Evaluable Par) GSK MDI	0.35 Errors Standard Deviation 1.139	NA Errors Standard Deviation NA NA indicates that the par did not receive the inhaler in that particular study.
Number of Errors Per Participant for Each Inhaler After 28 Days of Use (All Evaluable Par) AZ MDI	NA Errors Standard Deviation NA NA indicates that the par did not receive the inhaler in that particular study.	0.21 Errors Standard Deviation 0.838

SECONDARY outcome

Timeframe: Up to Day 56

Population: MITT Population

The number of errors for each inhaler (ELLIPTA and GSK MDI or AZ MDI) in par with one or more errors were evaluated based on the information collected in the Correct Use Checklists. The number of errors per par was summarised as continuous data by inhaler for each of the ELLIPTA versus MDI comparisons. NA indicates that the par. did not receive the inhaler in that particular sub-study. Only those par who made at least one error were included in the summary (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	Sub-Study 1 n=157 Participants Par were randomized to treatment sequence 3 or 4. In treatment sequence 3, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo GSK MDI at Visit 2 for treatment period 2. In treatment sequence 4, the par were dispensed Placebo GSK MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. GSK MDI contained propellant (1,1,1,2-Tetrafluoroethane). ELLIPTA DPI was taken as one inhalation, once daily and GSK MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.	Sub-Study 2 n=153 Participants Par were randomized to treatment sequence 1 or 2. In treatment sequence 1, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo AZ MDI at Visit 2 for treatment period 2. In treatment sequence 2, the par were dispensed Placebo AZ MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. AZ MDI was a placebo inhaler containing liquid aerosol. ELLIPTA DPI was taken as one inhalation, once daily and AZ MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.
Number of Errors Per Participant for Each After 28 Days of Use (Par With at Least One Error) ELLIPTA; n=7, 3	1.57 Errors Standard Deviation 1.134	2.00 Errors Standard Deviation 1.000
Number of Errors Per Participant for Each After 28 Days of Use (Par With at Least One Error) GSK MDI; n=25, 0	2.20 Errors Standard Deviation 2.062	—
Number of Errors Per Participant for Each After 28 Days of Use (Par With at Least One Error) AZ MDI; n=0, 14	—	2.29 Errors Standard Deviation 1.773

POST_HOC outcome

Timeframe: Up to Day 56

Population: MITT

A supportive post-hoc analysis on the primary endpoint was performed to address possible concerns due to the exclusion of data from a large number of participants who made no errors or at least one error on either inhaler tested in the primary analysis (only discordant cases involved in the analysis). For each ELLIPTA versus MDI comparison separately (Sub-study 1: Ellipta vs GSK MDI and Sub-study 2: Ellipta vs AZ MDI), the percentage of par having zero errors in inhaler use at Day 28 was analyzed using a Conditional Logistic Regression adjusting for treatment (inhaler) and treatment period. NA indicates that the par did not receive the inhaler in that particular sub-study.

Outcome measures

Outcome measures
Measure	Sub-Study 1 n=157 Participants Par were randomized to treatment sequence 3 or 4. In treatment sequence 3, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo GSK MDI at Visit 2 for treatment period 2. In treatment sequence 4, the par were dispensed Placebo GSK MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. GSK MDI contained propellant (1,1,1,2-Tetrafluoroethane). ELLIPTA DPI was taken as one inhalation, once daily and GSK MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.	Sub-Study 2 n=153 Participants Par were randomized to treatment sequence 1 or 2. In treatment sequence 1, the par were dispensed Placebo ELLIPTA DPI at Visit 1 for treatment period 1 and Placebo AZ MDI at Visit 2 for treatment period 2. In treatment sequence 2, the par were dispensed Placebo AZ MDI at Visit 1 for treatment period 1 and Placebo ELLIPTA DPI at Visit 2 for treatment period 2. ELLIPTA was a two strip inhaler with one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. AZ MDI was a placebo inhaler containing liquid aerosol. ELLIPTA DPI was taken as one inhalation, once daily and AZ MDI was taken as two inhalations, twice daily. Par continued taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period.
Percentage of Participants With Zero Errors in ELLIPTA DPI Versus GSK MDI and AZ MDI After 28 Days of Use in Each Treatment Phase Zero Errors after 28 Days of Use ELLIPTA	96 Percentage of Participants	98 Percentage of Participants
Percentage of Participants With Zero Errors in ELLIPTA DPI Versus GSK MDI and AZ MDI After 28 Days of Use in Each Treatment Phase Zero Errors after 28 Days of Use GSK MDI	84 Percentage of Participants	NA Percentage of Participants NA indicates that the par. did not receive the inhaler in that particular sub-study.
Percentage of Participants With Zero Errors in ELLIPTA DPI Versus GSK MDI and AZ MDI After 28 Days of Use in Each Treatment Phase Zero Errors after 28 Days of Use AZ MDI	NA Percentage of Participants NA indicates that the par. did not receive the inhaler in that particular sub-study.	91 Percentage of Participants
Percentage of Participants With Zero Errors in ELLIPTA DPI Versus GSK MDI and AZ MDI After 28 Days of Use in Each Treatment Phase At least one Error after 28 Days of Use ELLIPTA	4 Percentage of Participants	2 Percentage of Participants
Percentage of Participants With Zero Errors in ELLIPTA DPI Versus GSK MDI and AZ MDI After 28 Days of Use in Each Treatment Phase At least one Error after 28 Days of Use GSK MDI	16 Percentage of Participants	NA Percentage of Participants NA indicates that the par. did not receive the inhaler in that particular sub-study.
Percentage of Participants With Zero Errors in ELLIPTA DPI Versus GSK MDI and AZ MDI After 28 Days of Use in Each Treatment Phase At least one Error after 28 Days of Use AZ MDI	NA Percentage of Participants NA indicates that the par. did not receive the inhaler in that particular sub-study.	9 Percentage of Participants

Adverse Events

Sub-Study 1 - Ellipta (Sequence 3,4)

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Sub-Study 1 - GSK MDI (Sequence 3,4)

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Sub-Study 2 - Ellipta (Sequence 1,2)

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Sub-Study 2 - AZ MDI (Sequence 1,2)

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER