Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
DISKUS, HandiHaler, COPD, Placebo, Cross-over, Dry powder inhaler, ELLIPTA
Brief summary
This randomized, cross over study aims to find out the benefits of delivering triple therapy using a single ELLIPTA® DPI (fixed-dose combination triple therapy) versus delivering triple therapy using two different types of inhalers (open triple therapy) including DISKUS® with HandiHaler® to subjects with COPD. Correct inhaler use, critical errors and performance attributes will also be assessed. Approximately 240 subjects with COPD will be randomized in the study. The study will be conducted in 3 visits and will be completed in approximately 56 days. At Visit 1 (Day 1) and Visit 2 (Day 28) subjects will be randomized to receive a placebo ELLIPTA inhaler once daily (QD) or a placebo DISKUS twice daily (BID) with placebo HandiHaler QD inhaler in 1:1 ratio in a cross-over manner for the study period (28 days for each period). At Visit 3 (Day 56), subjects will be asked to complete preference questionnaire 1 or 2. There will be no active treatment and subjects will continue to take their own prescribed COPD maintenance and rescue medication during the entire study period. ELLIPTA and DISKUS are the registered trademarks of GlaxoSmithKline group of companies. HandiHaler is the registered trademark of Boehringer Ingelheim group of companies.
Interventions
DEVICEELLIPTA placebo DPI
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.
DEVICEDISKUS placebo DPI
DISKUS is a dry powder inhaler used via oral route. It will be a placebo DPI with one blister strip that will contain lactose monohydrate.
DEVICEHandiHaler placebo DPI
HandiHaler is a dry powder inhaler used via oral route. It will be a DPI with placebo capsules that will contain lactose monohydrate.
OTHERInhaler preference questionnaires
Preference questionnaires will be given to subjects to understand the inhaler preference. There will be 2 types of questionnaire, preference questionnaires 1 and 2, which will be randomized at visit 3 (Day 56).
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
This will an open-label study and blinding will not be performed.
Intervention model description
Subjects will be randomized to receive a placebo ELLIPTA inhaler QD or a placebo DISKUS BID with placebo HandiHaler QD inhaler at Visit 1 and Visit 2 in a cross-over manner followed by Preference Questionnaire 1 or 2
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Zero Errors After 28 Days of Inhaler Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Up to Day 56 | 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 |
| Percentage of Participants With Atleast One Error After 28 Days of Inhaler Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Up to Day 56 | 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 |
| Percentage of Participants With Atleast One Error After 28 Days of Inhaler Use in Each Treatment Phase (Supplementary Estimand: Composite) | Up to Day 56 | 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. |
| Percentage of Participants With Zero Errors After 28 Days of Inhaler Use in Each Treatment Phase(Supplementary Estimand: Composite) | Up to Day 56 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Errors for Each Treatment Group in Participants With One or More Errors After 28 Days of Use | Day 1 and Day 28 of each treatment group | 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. |
| Number of Participants With Zero Critical Errors After 28 Days of Each Treatment Group Use (Primary Estimand: Hypothetical) | Up to Day 56 | 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. |
| Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Up to Day 56 | 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 |
| Number of Participants With Atleast One Critical Error After 28 Days of Each Treatment Group Use (Supplementary Estimand: Composite) | Up to Day 56 | 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. |
| Number of Participants With Atleast One Critical Error After 28 Days of Each Treatment Group Use (Primary Estimand: Hypothetical) | Up to Day 56 | 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. |
| Number of Errors Per Participant for Each Treatment Group After 28 Days of Use (Primary Estimand: Hypothetical) | Up to Day 56 | 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. |
| Change in Errors Per Participant for Each Treatment Group After 28 Days of Use | Day 1 and Day 28 of each treatment group | 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. |
| Number of Errors for Each Treatment Group in Participants With One or More Errors After 28 Days of Use (Primary Estimand: Hypothetical) | Up to Day 56 | 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. |
Countries
United States
Participant flow
Recruitment details
This is a randomized, multi-center, open-label study comparing placebo ELLIPTA with placebo DISKUS + HandiHaler to assess correct inhaler use in participants with Chronic Obstructive Pulmonary Disease (COPD). A total of 17 centers across United States participated in the study.
Pre-assignment details
Out of 240 randomized participants (par), 239 entered the study as 1 par was randomized in error. In order to minimize potential bias the order of placebo devices & order of responses, in preference questionnaire (PQ), was randomized in a crossover design. All par on study received placebo only & participant flow reflects this as the only treatment
Participants by arm
| Arm | Count |
|---|---|
| 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. | 239 |
| Total | 239 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 (28 Days) | Adverse Event | 1 | 2 | 0 | 1 |
| Period 1 (28 Days) | Protocol Violation | 1 | 0 | 0 | 0 |
| Period 1 (28 Days) | Withdrawal by Subject | 0 | 0 | 1 | 1 |
| Period 2 (28 Days) | Adverse Event | 1 | 0 | 2 | 1 |
| Period 2 (28 Days) | Protocol Violation | 0 | 0 | 0 | 1 |
| Period 2 (28 Days) | Withdrawal by Subject | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 65.9 Years STANDARD_DEVIATION 8.25 |
| Race/Ethnicity, Customized African American/African Heritage | 23 Count of Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 3 Count of Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 213 Count of Participants |
| Sex: Female, Male Female | 108 Participants |
| Sex: Female, Male Male | 131 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 239 |
| other Total, other adverse events | 0 / 239 |
| serious Total, serious adverse events | 10 / 239 |
Outcome results
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
Time frame: Up to Day 56
Population: ITT Population. Only those participants with data available at specified time point were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ELLIPTA | Percentage of Participants With Atleast One Error After 28 Days of Inhaler Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Atleast 1 error-ELLIPTA&0 errors-DISKUS+HandiHaler | 3 Percentage of participants |
| ELLIPTA | Percentage of Participants With Atleast One Error After 28 Days of Inhaler Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Atleast 1error-DISKUS+HandiHaler&0errors-ELLIPTA | 23 Percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
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.
Time frame: Up to Day 56
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ELLIPTA | Percentage of Participants With Atleast One Error After 28 Days of Inhaler Use in Each Treatment Phase (Supplementary Estimand: Composite) | Atleast 1 error-ELLIPTA&0 errors-DISKUS+HandiHaler | 4 Percentage of participants |
| ELLIPTA | Percentage of Participants With Atleast One Error After 28 Days of Inhaler Use in Each Treatment Phase (Supplementary Estimand: Composite) | Atleast 1error-DISKUS+HandiHaler&0errors-ELLIPTA | 27 Percentage of participants |
p-value: <0.001Cochran-Mantel-Haenszel
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
Time frame: Up to Day 56
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ELLIPTA | Percentage of Participants With Zero Errors After 28 Days of Inhaler Use in Each Treatment Phase (Primary Estimand: Hypothetical) | 96 Percentage of participants |
| DISKUS + HANDIHALER | Percentage of Participants With Zero Errors After 28 Days of Inhaler Use in Each Treatment Phase (Primary Estimand: Hypothetical) | 87 Percentage of participants |
p-value: <0.00195% CI: [1.97, 54.28]stratified exact logistic model
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.
Time frame: Up to Day 56
Population: ITT Population. Only those participants with data available at specified time point were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ELLIPTA | Percentage of Participants With Zero Errors After 28 Days of Inhaler Use in Each Treatment Phase(Supplementary Estimand: Composite) | 95 Percentage of participants |
| DISKUS + HANDIHALER | Percentage of Participants With Zero Errors After 28 Days of Inhaler Use in Each Treatment Phase(Supplementary Estimand: Composite) | 85 Percentage of participants |
p-value: <0.00195% CI: [2.08, 24.55]stratified exact logistic model
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.
Time frame: Day 1 and Day 28 of each treatment group
Population: ITT Population. Only those participants with data available at specified time point were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ELLIPTA | Change in Errors for Each Treatment Group in Participants With One or More Errors After 28 Days of Use | 0.7 Errors per participant |
| DISKUS + HANDIHALER | Change in Errors for Each Treatment Group in Participants With One or More Errors After 28 Days of Use | 2.6 Errors per participant |
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.
Time frame: Day 1 and Day 28 of each treatment group
Population: ITT Population. Only those participants with data available at specified time point were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ELLIPTA | Change in Errors Per Participant for Each Treatment Group After 28 Days of Use | 0.0 Errors per participant |
| DISKUS + HANDIHALER | Change in Errors Per Participant for Each Treatment Group After 28 Days of Use | 0.0 Errors per participant |
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
Time frame: Up to Day 56
Population: ITT Population. Only those participants with data available at specified time point were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par closed the cover of the inhaler | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par takes long steady deep breath in through mouth | 2 Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par heard or felt the capsule vibrate | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par breathed out slowly | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par breathes out slowly and gently | 1 Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par closed lips tightly around mouthpiece | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par removed Diskus from mouth,held breath for long | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par opened cover | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par placed capsule in center chamber of inhaler | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par took a quick deep breath through the Diskus | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par slid lever away from mouthpiece | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par held breath for few seconds & removed inhaler | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par didn't tilt/shake device post dose preparation | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par exhaled fully | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par opened only 1 capsule from the blister card | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par resumed normal breathing | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par breathed in deeply | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par opened mouthpiece & center chamber is showing | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par didn't pierce use capsule for 2nd inhalation | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par didn't block air intake vents with fingers | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par did not exhale into the mouthpiece | NA Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par exhales while holding inhaler away from mouth | 6 Errors |
| ELLIPTA | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par pressed green piercing button&released button | NA Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par placed capsule in center chamber of inhaler | NA Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par closed lips tightly around mouthpiece | NA Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par didn't block air intake vents with fingers | NA Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par breathed in deeply | NA Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par heard or felt the capsule vibrate | NA Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par held breath for few seconds & removed inhaler | NA Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par resumed normal breathing | NA Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par didn't pierce use capsule for 2nd inhalation | NA Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par exhales while holding inhaler away from mouth | 9 Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par takes long steady deep breath in through mouth | NA Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par breathes out slowly and gently | NA Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par opened cover | 1 Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par slid lever away from mouthpiece | 1 Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par didn't tilt/shake device post dose preparation | 2 Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par took a quick deep breath through the Diskus | 1 Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par removed Diskus from mouth,held breath for long | 2 Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par breathed out slowly | 1 Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par closed the cover of the inhaler | 2 Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par opened mouthpiece & center chamber is showing | NA Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par opened only 1 capsule from the blister card | NA Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par did not exhale into the mouthpiece | NA Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par pressed green piercing button&released button | NA Errors |
| DISKUS + HANDIHALER | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par exhaled fully | NA Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par breathed in deeply | 10 Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par breathed out slowly | NA Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par exhales while holding inhaler away from mouth | 14 Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par exhaled fully | 7 Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par closed the cover of the inhaler | NA Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par didn't pierce use capsule for 2nd inhalation | 1 Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par did not exhale into the mouthpiece | 10 Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par resumed normal breathing | 9 Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par pressed green piercing button&released button | 4 Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par opened mouthpiece & center chamber is showing | 1 Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par held breath for few seconds & removed inhaler | 10 Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par didn't block air intake vents with fingers | 9 Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par opened only 1 capsule from the blister card | 5 Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par slid lever away from mouthpiece | NA Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par heard or felt the capsule vibrate | 14 Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par didn't tilt/shake device post dose preparation | 1 Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par opened cover | NA Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par closed lips tightly around mouthpiece | 9 Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par took a quick deep breath through the Diskus | NA Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par breathes out slowly and gently | NA Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par placed capsule in center chamber of inhaler | 1 Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par removed Diskus from mouth,held breath for long | NA Errors |
| HandiHaler | Number of Errors by Type for Each Inhaler After 28 Days of Use in Each Treatment Phase (Primary Estimand: Hypothetical) | Par takes long steady deep breath in through mouth | NA Errors |
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.
Time frame: Up to Day 56
Population: ITT Population. Only those participants with data available at specified time point were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ELLIPTA | Number of Errors for Each Treatment Group in Participants With One or More Errors After 28 Days of Use (Primary Estimand: Hypothetical) | 1.0 Errors per participant |
| DISKUS + HANDIHALER | Number of Errors for Each Treatment Group in Participants With One or More Errors After 28 Days of Use (Primary Estimand: Hypothetical) | 4.4 Errors per participant |
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.
Time frame: Up to Day 56
Population: ITT Population. Only those participants with data available at specified time point were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ELLIPTA | Number of Errors Per Participant for Each Treatment Group After 28 Days of Use (Primary Estimand: Hypothetical) | 0.0 Errors per participant |
| DISKUS + HANDIHALER | Number of Errors Per Participant for Each Treatment Group After 28 Days of Use (Primary Estimand: Hypothetical) | 0.6 Errors per participant |
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.
Time frame: Up to Day 56
Population: ITT Population. Only those participants with data available at specified time point were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ELLIPTA | Number of Participants With Atleast One Critical Error After 28 Days of Each Treatment Group Use (Primary Estimand: Hypothetical) | Atleast 1 critical error with ELLIPTA | 1 Participants |
| ELLIPTA | Number of Participants With Atleast One Critical Error After 28 Days of Each Treatment Group Use (Primary Estimand: Hypothetical) | Atleast 1 critical error with DISKUS+HandiHaler | 23 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Number of Participants With Atleast One Critical Error After 28 Days of Each Treatment Group Use (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.
Time frame: Up to Day 56
Population: ITT Population. Only those participants with data available at specified time point were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ELLIPTA | Number of Participants With Atleast One Critical Error After 28 Days of Each Treatment Group Use (Supplementary Estimand: Composite) | Atleast 1 error-ELLIPTA&0 errors-DISKUS+HandiHaler | 3 Participants |
| ELLIPTA | Number of Participants With Atleast One Critical Error After 28 Days of Each Treatment Group Use (Supplementary Estimand: Composite) | Atleast 1error-DISKUS+HandiHaler&0errors-ELLIPTA | 27 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
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.
Time frame: Up to Day 56
Population: ITT Population. Only those participants with data available at specified time point were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ELLIPTA | Number of Participants With Zero Critical Errors After 28 Days of Each Treatment Group Use (Primary Estimand: Hypothetical) | 215 Participants |
| DISKUS + HANDIHALER | Number of Participants With Zero Critical Errors After 28 Days of Each Treatment Group Use (Primary Estimand: Hypothetical) | 193 Participants |
p-value: <0.001stratified exact logistic model