Comparative Study of ELLIPTA Dry Powder Inhaler (DPI) Ver... | NCT03227445

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Treatment sequence A	Experimental	Eligible subjects will use ELLIPTA DPI QD for 28 days in Period 1 followed by DISKUS BID with HandiHaler QD use for 28 days in Period 2. These subjects will then be asked to complete preference questionnaire 1 at Visit 3 (Day 56).	Device: ELLIPTA placebo DPI Device: DISKUS placebo DPI Device: HandiHaler placebo DPI Other: Inhaler preference questionnaires
Treatment sequence B	Experimental	Eligible subjects will use ELLIPTA DPI QD for 28 days in Period 1 followed by DISKUS BID with HandiHaler QD use for 28 days in Period 2. These subjects will then be asked to complete preference questionnaire 2 at Visit 3 (Day 56).	Device: ELLIPTA placebo DPI Device: DISKUS placebo DPI Device: HandiHaler placebo DPI Other: Inhaler preference questionnaires
Treatment sequence C	Experimental	Eligible subjects will use DISKUS BID with HandiHaler QD for 28 days in Period 1 followed by ELLIPTA DPI QD use for 28 days in Period 2. These subjects will then be asked to complete preference questionnaire 1 at Visit 3 (Day 56).	Device: ELLIPTA placebo DPI Device: DISKUS placebo DPI Device: HandiHaler placebo DPI Other: Inhaler preference questionnaires
Treatment sequence D	Experimental	Eligible subjects will use DISKUS BID with HandiHaler QD for 28 days in Period 1 followed by ELLIPTA DPI QD use for 28 days in Period 2. These subjects will then be asked to complete preference questionnaire 2 at Visit 3 (Day 56).

Interventions

Name	Type	Description	Arm Group Labels	Other Names
ELLIPTA placebo DPI	Device	ELLIPTA is a dry powder inhaler used via oral route. It will be a placebo DPI with two strips with 30 blisters per strip. First strip will contain lactose monohydrate and the second strip will contain lactose monohydrate blended with magnesium stearate.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Zero Errors After 28 Days of Inhaler Use in Each Treatment Phase (Primary Estimand: Hypothetical)	A checklist for correct use of each inhaler was developed in Patient Instruction Leaflets (PIL's). Participants were guided by trained health care provider (HCP) to demonstrate correct use of inhaler. Baseline assessment was conducted when participant initially dispensed the inhaler. Second assessment was conducted after each 28day dosing period. Correct Use Check list was completed by HCP at each visit. Primary hypothetical estimand is the estimate of treatment effect of all participants who stayed on their randomized study device sequence and did not change their standard COPD maintenance medication device to one delivered via ELLIPTA, DISKUS or HANDIHALER, throughout both 28 day treatment periods. Participants could attend visit without the device/s they were randomised to, in which case correct use cannot be assessed as described in the protocol. Participants who completed error assessments for both randomized treatment groups and experienced no intercurrent events were included	Up to Day 56
Percentage of Participants With Atleast One Error After 28 Days of Inhaler Use in Each Treatment Phase (Primary Estimand: Hypothetical)	Primary estimand is the treatment effect estimated in participants who stayed on their randomised study device sequence and did not change their standard COPD maintenance medication device to one delivered via ELLIPTA, DISKUS or HANDIHALER, throughout both 28 day treatment periods. The participant could attend the visit without the device/s they were randomised to, in which case correct use cannot be assessed as described in the protocol. For primary estimand, a sensitivity analysis using Cochran-Mantel-Haenszel test was performed on participants with discordant results. Only those participants who completed error assessments for both randomized treatment groups and experienced no intercurrent events were included	Up to Day 56
Percentage of Participants With Atleast One Error After 28 Days of Inhaler Use in Each Treatment Phase (Supplementary Estimand: Composite)	Supplementary estimand estimated the composite effect of initial randomized treatment. A sensitivity analysis using the Cochran-Mantel-Haenszel test was performed on participants with discordant results. Participants who withdrew during period 2 were included in the analysis using early withdrawal data where available or imputation otherwise. Participants who experienced an intercurrent event in Period 1 were excluded from the analysis.

Secondary Outcomes

Measure	Description	Time Frame
Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical)	The occurrence of each type of error for each inhaler (ELLIPTA, DISKUS or HANDIHALER) were evaluated based on the information collected in Correct Use Checklists. Primary estimand is the treatment effect estimated in participants who stayed on their randomised study device sequence & did not change their standard COPD maintenance medication device to one delivered via ELLIPTA, DISKUS or HANDIHALER, throughout both 28 day treatment periods. The participant could attend the visit without the device/s they were randomised to, in which case correct use cannot be assessed as described in the protocol. For primary estimand, a sensitivity analysis using Cochran-Mantel-Haenszel test was performed on participants with discordant results. Only those participants who completed error assessments for both randomized treatment groups & experienced no intercurrent events were included. The number of error is reported as NA for the type of error which was not applicable to the particular inhaler type

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects must be capable of giving signed informed consent.
Subjects must have a diagnosis of COPD with a documented history of COPD for at least 12 months, in accordance with the definition by the American Thoracic Society/European Respiratory Society.
Subjects must be 40 years of age inclusive, at the time of signing the informed consent.
Male or female subjects will be included. Females must not be pregnant or planning pregnancy during the study or not lactating.
Subjects must have a documented post albuterol forced expiratory volume in one second (FEV1)/ forced vital capacity (FVC) ratio <0.70 and FEV1 <=70% of predicted obtained within two years of Visit 1.
Current or former (defined as subjects who have quit smoking for at least 3 months prior to Screening/Visit 1) cigarette smokers with a > 10 pack-year smoking history [Number of pack-years = (number of cigarettes per day/20) x number of years smoked (example, 10 pack-years is equal to 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years].
All subjects should be currently receiving maintenance treatment for COPD for at least 4 weeks prior to Randomization/Visit 1 and evaluated as unlikely to change COPD treatment within 4 weeks of Visit 1.
All subjects should be able to stay on their prescribed maintenance COPD inhaler (s) without change throughout the entire treatment period.
Subjects must be able to read, comprehend, and record information in English.

Exclusion Criteria:

Subjects must not have a current diagnosis of asthma.
Subjects must not have used the ELLIPTA, DISKUS, or HandiHaler inhalers in the 12 months prior to Visit 1.
Subjects must not be receiving their current COPD medications with the ELLIPTA, DISKUS, or HandiHaler inhalers.
Subjects must not be receiving only inhaled short-acting beta-adrenergic agonists, i.e., albuterol as their daily COPD therapy (as needed or regularly scheduled).
Subjects must not have experienced more than 1 COPD exacerbation which required hospitalization in the 12 months prior to Visit 1.
Subjects must not have a known or suspected history of alcohol or drug abuse within the last 2 years.
Subjects must not have a history of hypersensitivity to any component of the study inhalers (example, lactose, magnesium stearate). In addition, subjects with a history of severe milk protein allergy that, in the opinion of the study physician, contraindicates participation will also be excluded.
Subjects with other respiratory disorders, including active tuberculosis, active lung cancer, sarcoidosis, lung fibrosis, pulmonary hypertension, or pulmonary disease (including but not confined to asthma, bronchiectasis with the need for treatment, cystic fibrosis, and bronchopulmonary dysplasia), interstitial lung diseases or other active pulmonary diseases.
Subjects with historical, or current evidence of clinically significant or rapidly progressing or unstable cardiovascular, neurological, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the participant at risk through participation, or which would affect the analysis if the disease/condition exacerbated during the study will be excluded.
Subjects with history of psychiatric disease, intellectual impairment, poor motivation or other conditions that will limit the validity of informed consent to participate in the study will be excluded.
Subjects at risk of non-compliance, or unable to comply with the study procedures, or unable to continue their current medications.
Subjects who have received an investigational drug and/or medical device/inhaler within 30 days of entry into this study (Screening/Visit 1), or within five drug half-lives of the investigational drug, whichever is longer.
Subjects will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub investigator, study coordinator, or employee of the participating investigator.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Orlando	Florida	32825	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
32324983	Background	Kerwin EM, Spangenthal S, Zvarich M, Millar V, Jain R, Collison K, Sharma R. ELLIPTA Versus DISKUS plus HandiHaler in COPD: A Randomized, Open-Label, Crossover Study in a Clinical Trial Setting. Chronic Obstr Pulm Dis. 2020 Apr;7(2):118-129. doi: 10.15326/jcopdf.7.2.2019.0153.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	ELLIPTA/DISKUS+HANDIHALER/Q1	Participants received placebo via ELLIPTA dry powder inhaler (DPI) in period 1 and DISKUS DPI + HandiHaler in period 2, followed by preference questionnaire (PQ) version 1. There was no active treatment and participants continued to take their own prescribed COPD medication and rescue medications for the duration of the study

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 17, 2017	Nov 16, 2018

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Zero Errors After 28 Days of Inhaler Use in Each Treatment Phase (Primary Estimand: Hypothetical)

A checklist for correct use of each inhaler was developed in Patient Instruction Leaflets (PIL's). Participants were guided by trained health care provider (HCP) to demonstrate correct use of inhaler. Baseline assessment was conducted when participant initially dispensed the inhaler. Second assessment was conducted after each 28day dosing period. Correct Use Check list was completed by HCP at each visit. Primary hypothetical estimand is the estimate of treatment effect of all participants who stayed on their randomized study device sequence and did not change their standard COPD maintenance medication device to one delivered via ELLIPTA, DISKUS or HANDIHALER, throughout both 28 day treatment periods. Participants could attend visit without the device/s they were randomised to, in which case correct use cannot be assessed as described in the protocol. Participants who completed error assessments for both randomized treatment groups and experienced no intercurrent events were included

Intent-to-treat (ITT) Population comprised of all randomized participants, excluding those who were randomized in error, and did not have at least one error assessment at Visit 1. Only those participants with data available at specified time point were analyzed.

Posted

Number

Percentage of participants

Up to Day 56

ID	Title	Description
OG000	ELLIPTA	Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.
OG001	DISKUS + HANDIHALER	Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.

Units	Counts
Participants	OG000217 OG001217

Title

Denominators

Categories

Title	Measurements
	OG00096 OG00187

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		stratified exact logistic model		<0.001		Odds Ratio (OR)	6.88			2-Sided	95	1.97	54.28			Participants included in the model as fixed strata, treatment option was included in the exact statement and period included as fixed effects.		Superiority		There are three intercurrent events identified which could impact upon the estimand of interest: The participant could withdraw from randomised study device sequence and therefore withdraw from the study The participant could change their standard COPD maintenance medication device to one delivered via ELLIPTA, DISKUS or HANDIHALER; these subjects should have been withdrawn from the study according to the protocol. The participant could attend the visit without the device/s they were randomised to, in which case correct use cannot be assessed as described in the protocol. Rescue Medication use and change to maintenance COPD medication which is not delivered via ELLIPTA, DISKUS or HANDIHALER are not considered intercurrent events

Secondary

Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical)

The occurrence of each type of error for each inhaler (ELLIPTA, DISKUS or HANDIHALER) were evaluated based on the information collected in Correct Use Checklists. Primary estimand is the treatment effect estimated in participants who stayed on their randomised study device sequence & did not change their standard COPD maintenance medication device to one delivered via ELLIPTA, DISKUS or HANDIHALER, throughout both 28 day treatment periods. The participant could attend the visit without the device/s they were randomised to, in which case correct use cannot be assessed as described in the protocol. For primary estimand, a sensitivity analysis using Cochran-Mantel-Haenszel test was performed on participants with discordant results. Only those participants who completed error assessments for both randomized treatment groups & experienced no intercurrent events were included. The number of error is reported as NA for the type of error which was not applicable to the particular inhaler type

ITT Population. Only those participants with data available at specified time point were analyzed.

Posted

Number

Errors

Up to Day 56

ID	Title	Description
OG000	ELLIPTA	Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.
OG001	DISKUS	Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.

Primary

Percentage of Participants With Atleast One Error After 28 Days of Inhaler Use in Each Treatment Phase (Primary Estimand: Hypothetical)

Primary estimand is the treatment effect estimated in participants who stayed on their randomised study device sequence and did not change their standard COPD maintenance medication device to one delivered via ELLIPTA, DISKUS or HANDIHALER, throughout both 28 day treatment periods. The participant could attend the visit without the device/s they were randomised to, in which case correct use cannot be assessed as described in the protocol. For primary estimand, a sensitivity analysis using Cochran-Mantel-Haenszel test was performed on participants with discordant results. Only those participants who completed error assessments for both randomized treatment groups and experienced no intercurrent events were included

ITT Population. Only those participants with data available at specified time point were analyzed.

Posted

Number

Percentage of participants

Up to Day 56

ID	Title	Description
OG000	All Study Participants	Participants received placebo via ELLIPTA dry powder inhaler (DPI) or DISKUS DPI in combination with HandiHaler DPI based on the following treatment sequences: Treatment Sequence A (ELLIPTA in period 1 and DISKUS + HandiHaler in period 2, followed by PQ 1.); Treatment Sequence B (ELLIPTA in period 1 and DISKUS + HandiHaler in period 2, followed by PQ2); Treatment Sequence C (DISKUS + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ1); or Treatment Sequence D (DISKUS + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ2). Participants continued to take their own prescribed COPD medication and rescue medications for the entire 56-day study period. All participants on study received placebo only and participant flow reflects this as the only treatment.

Secondary

Number of Errors Per Participant for Each Treatment Group After 28 Days of Use (Primary Estimand: Hypothetical)

Participants were provided with PIL explaining correct use of inhaler. Overall error includes both critical and non-critical errors. Primary estimand is the treatment effect estimated in participants who stayed on their randomised study device sequence and did not change their standard COPD maintenance medication device to one delivered via ELLIPTA, DISKUS or HANDIHALER, throughout both 28 day treatment periods. The participant could attend the visit without the device/s they were randomised to, in which case correct use cannot be assessed as described in the protocol. For primary estimand, a sensitivity analysis using Cochran-Mantel-Haenszel test was performed on participants with discordant results. Only those participants who completed error assessments for both randomized treatment groups and experienced no intercurrent events were included.

ITT Population. Only those participants with data available at specified time point were analyzed.

Posted

Median

Full Range

Errors per participant

Up to Day 56

ID	Title	Description
OG000	ELLIPTA	Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.
OG001	DISKUS + HandiHaler	Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.

Secondary

Change in Errors Per Participant for Each Treatment Group After 28 Days of Use

Assessment of errors was conducted by HCP trained in the correct inhaler use of the three inhalers based on the checklist of errors. The median number of overall errors made by per participant was assessed for ELLIPTA and DISKUS + HandiHaler both on Day 1 and Day 28 for each treatment group. The difference was calculated by subtracting values of Day 28 from Day1 for each treatment regimen. Only those participants who completed error assessments for both randomized treatment groups and experienced no intercurrent events were included.

ITT Population. Only those participants with data available at specified time point were analyzed.

Posted

Median

Full Range

Errors per participant

Day 1 and Day 28 of each treatment group

ID	Title	Description
OG000	ELLIPTA	Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.
OG001	DISKUS + HandiHaler	Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.

Units	Counts
Participants

Secondary

Number of Errors for Each Treatment Group in Participants With One or More Errors After 28 Days of Use (Primary Estimand: Hypothetical)

Participants were provided with the PIL, explaining correct use of the inhaler. Overall error includes both critical and non-critical errors. Assessment of errors was conducted by HCP trained in the correct inhaler use of the three inhalers based on the checklist of errors. Primary estimand is the treatment effect estimated in participants who stayed on their randomised study device sequence and did not change their standard COPD maintenance medication device to one delivered via ELLIPTA, DISKUS or HANDIHALER, throughout both 28 day treatment periods. The participant could attend the visit without the device/s they were randomised to, in which case correct use cannot be assessed as described in the protocol. For primary estimand, a sensitivity analysis using Cochran-Mantel-Haenszel test was performed on participants with discordant results. Only those participants who completed error assessments for both randomized treatment groups and experienced no intercurrent events were included.

ITT Population. Only those participants with data available at specified time point were analyzed.

Posted

Median

Full Range

Errors per participant

Up to Day 56

ID	Title	Description
OG000	ELLIPTA	Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.
OG001	DISKUS + HandiHaler	Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.

Secondary

Change in Errors for Each Treatment Group in Participants With One or More Errors After 28 Days of Use

Assessment of errors was conducted by health care professionals trained in the correct inhaler use of the three inhalers based on the checklist of errors. The median of overall errors made by each participant was assessed for ELLIPTA and DISKUS + HandiHaler both on Day 1 and Day 28. The difference was calculated by subtracting values of Day 28 from Day1 for each treatment regimen. Only those participants who completed error assessments for both randomized treatment groups and experienced no intercurrent events were included.

ITT Population. Only those participants with data available at specified time point were analyzed.

Posted

Median

Full Range

Errors per participant

Day 1 and Day 28 of each treatment group

ID	Title	Description
OG000	ELLIPTA	Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.
OG001	DISKUS + HandiHaler	Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.

Units	Counts
Participants

Secondary

Number of Participants With Zero Critical Errors After 28 Days of Each Treatment Group Use (Primary Estimand: Hypothetical)

A checklist for correct use of each inhaler was developed based on the steps identified in the PIL. A critical error was defined as an error that was most likely to result in no, or a significantly reduced amount, of medication being inhaled by the participant. Primary estimand is the treatment effect estimated in participants who stayed on their randomised study device sequence and did not change their standard COPD maintenance medication device to one delivered via ELLIPTA, DISKUS or HANDIHALER, throughout both 28 day treatment periods. The participant could attend the visit without the device/s they were randomised to, in which case correct use cannot be assessed as described in the protocol. For primary estimand, a sensitivity analysis using Cochran-Mantel-Haenszel test was performed on participants with discordant results. Only those participants who completed error assessments for both randomized treatment groups and experienced no intercurrent events were included.

ITT Population. Only those participants with data available at specified time point were analyzed.

Posted

Count of Participants

Participants

Up to Day 56

ID	Title	Description
OG000	ELLIPTA	Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.
OG001	DISKUS + HandiHaler	Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.

Primary

Percentage of Participants With Atleast One Error After 28 Days of Inhaler Use in Each Treatment Phase (Supplementary Estimand: Composite)

Supplementary estimand estimated the composite effect of initial randomized treatment. A sensitivity analysis using the Cochran-Mantel-Haenszel test was performed on participants with discordant results. Participants who withdrew during period 2 were included in the analysis using early withdrawal data where available or imputation otherwise. Participants who experienced an intercurrent event in Period 1 were excluded from the analysis.

Posted

Number

Percentage of participants

Up to Day 56

ID	Title	Description
OG000	All Study Participants	Participants received placebo via ELLIPTA dry powder inhaler (DPI) or DISKUS DPI in combination with HandiHaler DPI based on the following treatment sequences: Treatment Sequence A (ELLIPTA in period 1 and DISKUS + HandiHaler in period 2, followed by PQ 1.); Treatment Sequence B (ELLIPTA in period 1 and DISKUS + HandiHaler in period 2, followed by PQ2); Treatment Sequence C (DISKUS + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ1); or Treatment Sequence D (DISKUS + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ2). Participants continued to take their own prescribed COPD medication and rescue medications for the entire 56-day study period. All participants on study received placebo only and participant flow reflects this as the only treatment.

Units	Counts

Secondary

Number of Participants With Atleast One Critical Error After 28 Days of Each Treatment Group Use (Primary Estimand: Hypothetical)

A critical error was defined as an error that was most likely to result in no, or a significantly reduced amount, of medication being inhaled by the participant. Primary estimand is the treatment effect estimated in participants who stayed on their randomised study device sequence and did not change their standard COPD maintenance medication device to one delivered via ELLIPTA, DISKUS or HANDIHALER, throughout both 28 day treatment periods. The participant could attend the visit without the device/s they were randomised to, in which case correct use cannot be assessed as described in the protocol. For primary estimand, a sensitivity analysis using Cochran-Mantel-Haenszel test was performed on participants with discordant results. Only those participants who completed error assessments for both randomized treatment groups and experienced no intercurrent events were included.

ITT Population. Only those participants with data available at specified time point were analyzed.

Posted

Number

Participants

Up to Day 56

ID	Title	Description
OG000	All Study Participants	Participants received placebo via ELLIPTA dry powder inhaler (DPI) or DISKUS DPI in combination with HandiHaler DPI based on the following treatment sequences: Treatment Sequence A (ELLIPTA in period 1 and DISKUS + HandiHaler in period 2, followed by PQ 1.); Treatment Sequence B (ELLIPTA in period 1 and DISKUS + HandiHaler in period 2, followed by PQ2); Treatment Sequence C (DISKUS + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ1); or Treatment Sequence D (DISKUS + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ2). Participants continued to take their own prescribed COPD medication and rescue medications for the entire 56-day study period. All participants on study received placebo only and participant flow reflects this as the only treatment.

Secondary

Number of Participants With Atleast One Critical Error After 28 Days of Each Treatment Group Use (Supplementary Estimand: Composite)

ITT Population. Only those participants with data available at specified time point were analyzed.

Posted

Count of Participants

Participants

Up to Day 56

ID	Title	Description
OG000	All Study Participants	Participants received placebo via ELLIPTA dry powder inhaler (DPI) or DISKUS DPI in combination with HandiHaler DPI based on the following treatment sequences: Treatment Sequence A (ELLIPTA in period 1 and DISKUS + HandiHaler in period 2, followed by PQ 1.); Treatment Sequence B (ELLIPTA in period 1 and DISKUS + HandiHaler in period 2, followed by PQ2); Treatment Sequence C (DISKUS + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ1); or Treatment Sequence D (DISKUS + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ2). Participants continued to take their own prescribed COPD medication and rescue medications for the entire 56-day study period. All participants on study received placebo only and participant flow reflects this as the only treatment.

Primary

Percentage of Participants With Zero Errors After 28 Days of Inhaler Use in Each Treatment Phase(Supplementary Estimand: Composite)

Supplementary estimand estimated the composite effect of initial randomized treatment. The analysis was performed using stratified exact logistic model. Participants were included in the model as fixed strata, treatment option was included in the exact statement and period included as fixed effects. Participants who withdrew during period 2 were included in the analysis using early withdrawal data where available or imputation otherwise. Participants who experienced an intercurrent event in Period 1 were excluded from the analysis.

ITT Population. Only those participants with data available at specified time point were analyzed.

Posted

Number

Percentage of participants

Up to Day 56

ID	Title	Description
OG000	ELLIPTA	Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.
OG001	DISKUS + HandiHaler	Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0005 events5 affected239 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0002 events2 affected239 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected239 at risk
Pneumonia	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0003 events3 affected239 at risk
Bronchitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected239 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected239 at risk
Chest pain	General disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected239 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected239 at risk
Dysarthria	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected239 at risk
Hemiparesis	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected239 at risk

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms