NCT02982187

A Clinical Study Assessing Critical Errors, Training/Teaching Time, and Preference Attributes of the ELLIPTA® Dry Powder Inhaler, in Comparison to Combinations of Dry Powder Inhalers Used to Provide Triple Therapy, in Patients With Chronic Obstructive Pulmonary Disease

Completed Phase 4 Results posted Last updated 21 October 2019

What this trial tests

Phase 4 trial testing Placebo ELLIPTA in Pulmonary Disease, Chronic Obstructive in 160 participants. Completed in 19 June 2017.

Timeline

30 December 2016

Primary endpoint
19 June 2017

19 June 2017

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	none
Primary purpose	treatment
Enrollment	160
Start date	30 December 2016
Primary completion	19 June 2017
Estimated completion	19 June 2017
Sites	5 locations across United Kingdom, Netherlands

Drugs / interventions tested

• Placebo ELLIPTA
• Placebo DISKUS
• Placebo TURBUHALER
• Placebo HANDIHALER
• PQ1
• PQ2
• PQ3
• PQ4

Conditions studied

• Pulmonary Disease, Chronic Obstructive — all drugs for Pulmonary Disease, Chronic Obstructive →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

40 and older, any sex, with Pulmonary Disease, Chronic Obstructive. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Making at Least One Critical Error After Reading the Patient Information Leaflets (PIL) Primary · Day 1

Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. 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. After reading the PIL for each DPI to be tested, participants demonstrated the DPI and critical errors made by the participants while using each DPI were recorded by the Healthcare Professional (HCP) on the checklists provided. Percentage of participants making at least one critical error after reading PIL w

Group	Value	95% CI
Sub-study 1 : ELLIPTA	9
Sub-study 1 : DISKUS + HandiHaler	75
Sub-study 2 : ELLIPTA	9
Sub-study 2 : Turbuhaler + HandiHaler	73

Percentage of Participants Making at Least One Critical Error After the First Instruction From the HCP Secondary · Day 1

Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. 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. After reading PIL for each DPI to be tested, participants demonstrated the DPI and errors made by the participants while using each DPI were recorded by the HCP on the checklists provided. If a participant made errors while demonstrating DPI, HCP provided instruction on the correct use of the DPI. The partic

Group	Value	95% CI
Sub-study 1 : ELLIPTA	1
Sub-study 1 : DISKUS + HandiHaler	9
Sub-study 2 : ELLIPTA	3
Sub-study 2 : Turbuhaler + HandiHaler	14

Percentage of Participants Making at Least One Critical Error After the Second Instruction From the HCP Secondary · Day 1

Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. 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. After reading the PIL for each DPI to be tested, participants demonstrated the DPI and errors made by the participants while using each DPI were recorded by the HCP on the checklists provided. If a participant made an error while demonstrating DPI use after first instruction from the HCP, then the HCP provid

Group	Value	95% CI
Sub-study 1 : ELLIPTA	0
Sub-study 1 : DISKUS + HandiHaler	6
Sub-study 2 : ELLIPTA	0
Sub-study 2 : Turbuhaler + HandiHaler	5

Percentage of Participants Making at Least One Overall Error After Reading the PIL Secondary · Day 1

Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. Overall error was defined as an error including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL. For each DPI to be tested, overall errors including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL were recorded by the HCP on the checklists provided. Percentage of participants making at least one overall error after reading the PIL were reported.

Group	Value	95% CI
Sub-study 1 : ELLIPTA	24
Sub-study 1 : DISKUS + HandiHaler	80
Sub-study 2 : ELLIPTA	22
Sub-study 2 : Turbuhaler + HandiHaler	80

Percentage of Participants Making at Least One Overall Error After the First Instruction From the HCP Secondary · Day 1

For each DPI to be tested, overall errors including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL following first instruction from the HCP were recorded by the HCP on the checklists provided. Percentage of participants making at least one overall error after the first instruction from the HCP were reported.

Group	Value	95% CI
Sub-study 1 : ELLIPTA	5
Sub-study 1 : DISKUS + HandiHaler	15
Sub-study 2 : ELLIPTA	5
Sub-study 2 : Turbuhaler + HandiHaler	20

Percentage of Participants Making at Least One Overall Error After the Second Instruction From the HCP Secondary · Day 1

For each DPI to be tested, overall errors including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL following first, and second instruction from the HCP were recorded by the HCP on the checklists provided. Percentage of participants making at least one overall error after the second instruction from the HCP were reported. These statistics are only presented when the model has successfully converged.

Group	Value	95% CI
Sub-study 1 : ELLIPTA	4
Sub-study 1 : DISKUS + HandiHaler	8
Sub-study 2 : ELLIPTA	1
Sub-study 2 : Turbuhaler + HandiHaler	6

Number of Participants With Instructions (0, 1 or 2 Times) From the HCP Which Are Needed to Demonstrate Correct Inhaler Use Secondary · Day 1

In each sub-study, if the participant made error while demonstrating the use of the DPI after reading the PIL, the HCP demonstrated the correct usage instructions to the participant. The participant was then asked to demonstrate the DPI again. Any errors made were recorded by the HCP, and the same process was repeated one more time. In total, the HCP instructed the participants on the use of the DPI up to two times after which there were no assessment scheduled. Number of participants with instructions (0, 1 or 2) needed to demonstrate correct DPI use by the participants were reported.

Number of Instructions, 0

Group	Value	95% CI
Sub-study 1 : ELLIPTA	61
Sub-study 1 : DISKUS + HandiHaler	16
Sub-study 2 : ELLIPTA	62
Sub-study 2 : Turbuhaler + HandiHaler	16

Number of Instructions, 1

Group	Value	95% CI
Sub-study 1 : ELLIPTA	15
Sub-study 1 : DISKUS + HandiHaler	52
Sub-study 2 : ELLIPTA	13
Sub-study 2 : Turbuhaler + HandiHaler	47

Number of Instructions, 2

Group	Value	95% CI
Sub-study 1 : ELLIPTA	1
Sub-study 1 : DISKUS + HandiHaler	6
Sub-study 2 : ELLIPTA	3
Sub-study 2 : Turbuhaler + HandiHaler	11

Failed to demonstrate correct use

Group	Value	95% CI
Sub-study 1 : ELLIPTA	3
Sub-study 1 : DISKUS + HandiHaler	6
Sub-study 2 : ELLIPTA	1
Sub-study 2 : Turbuhaler + HandiHaler	5

The Median Time to Demonstrate Correct Inhaler Use (T1+T2) Secondary · Day 1

For each DPI being tested, the total time taken from when participant started reading the PIL until when correct use was demonstrated (that is the time required to read PIL, and two attempts for correct use of DPI following instructions provided by the HCP ) was recorded. A participant who did not demonstrate correct use at the end of the time period was censored. The median time to demonstrate correct DPI use (minutes) is taken from the Kaplan-Meier analysis. If more than 50% of the data is censored therefore the median is not applicable.

Group	Value	95% CI
Sub-study 1 : ELLIPTA	2.68	0.8 – 12.9
Sub-study 1 : DISKUS + HandiHaler	10.57	1.5 – 42.4
Sub-study 2 : ELLIPTA	2.58	0.7 – 25.2
Sub-study 2 : Turbuhaler + HandiHaler	11.30	3.3 – 55.8

Time Taken to Read the PIL and Demonstrate Correct Inhaler Use (T1) Secondary · Day 1

For each DPI being tested, the time taken from when participant started reading the PIL until when correct use was demonstrated with no need of instructions by HCP was reported. A participant who did not demonstrate correct use at the end of the time period was censored. The median time to demonstrate correct DPI use (minutes) is taken from the Kaplan-Meier analysis. If more than 50% of the data is censored therefore the median is not applicable.

Group	Value	95% CI
Sub-study 1 : ELLIPTA	2.88	0.8 – 7.2
Sub-study 1 : DISKUS + HandiHaler	NA	1.5 – 19.2
Sub-study 2 : ELLIPTA	2.78	0.7 – 8.6
Sub-study 2 : Turbuhaler + HandiHaler	NA	3.3 – 15.1

Time Taken to be Given Instruction by the HCP (up to 2 Times) on Use of the Inhaler and to Demonstrate Correct Inhaler Use (T2) Secondary · Day 1

The time in minutes from when the HCP started to instruct participant for the correct use of DPI until correct use was demonstrated including maximum of two attempts only, was recorded. A participant who did not demonstrate correct use at the end of the time period was censored. Participants who demonstrated correct use after reading the PIL (T1) were included with a time of 0 for T2. The median time to demonstrate correct DPI use (minutes) is taken from the Kaplan-Meier analysis. If more than 50% of the data is censored then the median is not applicable. Participants who demonstrated correct

Group	Value	95% CI
Sub-study 1 : ELLIPTA	0.00	0.0 – 3.3
Sub-study 1 : DISKUS + HandiHaler	2.89	0.0 – 16.5
Sub-study 2 : ELLIPTA	0.00	0.0 – 6.3
Sub-study 2 : Turbuhaler + HandiHaler	3.12	0.0 – 14.3

Number of Participants With Treatment Preference Based on Responses to the Preference Questionnaire, Which Considered the Number of Steps Required to Take the COPD Medication Secondary · Day 1

Participants demonstrated the use of ELLIPTA, and depending on the substudy DISKUS plus HandiHaler or Turbuhaler plus Handihaler. At the end of Visit 1, participants completed specific versions of the inhaler PQ (PQ1, PQ2, PQ3 or PQ4) according to the questionnaire they were randomized to. Participants assessed the inhaler preference based on the number of steps needed to take the COPD medication. Participants checked the response from the choice of ELLIPTA, DISKUS + HandiHaler (sub-study 1), Turbuhaler + Handihaler (sub-study 2) and No Preference. Number of participants with treatment prefere

ELLIPTA

Group	Value	95% CI
Sub Study 1: ELLIPTA vs DISKUS + HandiHaler	71
Sub Study 2: ELLIPTA vs Turbuhaler + HandiHaler	72

DISKUS + HandiHaler

Group	Value	95% CI
Sub Study 1: ELLIPTA vs DISKUS + HandiHaler	6
Sub Study 2: ELLIPTA vs Turbuhaler + HandiHaler	4

No Preference

Group	Value	95% CI
Sub Study 1: ELLIPTA vs DISKUS + HandiHaler	3
Sub Study 2: ELLIPTA vs Turbuhaler + HandiHaler	3

Number of Participants With Treatment Preference Based on Responses to the Preference Questionnaire, Which Considered Overall Treatment Preference Secondary · Day 1

Participants demonstrated the use of ELLIPTA, and depending on the substudy DISKUS plus HandiHaler or Turbuhaler plus Handihaler. At the end of Visit 1, participants completed specific versions of the inhaler PQ (PQ1, PQ2, PQ3 or PQ4) according to the questionnaire they were randomized to. Participants assessed the inhaler preference based on overall treatment preference. Participants checked the response from the choice of ELLIPTA, DISKUS + HandiHaler (sub-study 1), Turbuhaler + Handihaler (sub-study 2) and No Preference. Number of participants with treatment preference based on responses to

ELLIPTA

Group	Value	95% CI
Sub Study 1: ELLIPTA vs DISKUS + HandiHaler	65
Sub Study 2: ELLIPTA vs Turbuhaler + HandiHaler	66

DISKUS + HandiHaler

Group	Value	95% CI
Sub Study 1: ELLIPTA vs DISKUS + HandiHaler	7
Sub Study 2: ELLIPTA vs Turbuhaler + HandiHaler	3

No Preference

Group	Value	95% CI
Sub Study 1: ELLIPTA vs DISKUS + HandiHaler	8
Sub Study 2: ELLIPTA vs Turbuhaler + HandiHaler	10

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Sub Study 1: ELLIPTA vs DISKUS + HandiHaler

Serious: 0/80 (0%)

Deaths: 0/80

Sub Study 2: ELLIPTA vs Turbuhaler + HandiHaler

Serious: 0/79 (0%)

Deaths: 0/79

Other adverse events (1 terms — click to expand)

Reaction	System	Sub Study 1: ELLIPTA vs DI…	Sub Study 2: ELLIPTA vs Tu…
Laceration	Injury, poisoning and procedural complications	—	—

Data from ClinicalTrials.gov NCT02982187 adverse events section.

Sponsor's own description

This is a randomized, multi-centre, open-label, placebo-device, cross-over study, with a 2x2 complete block design in subjects with chronic obstructive pulmonary disease (COPD) to assess the benefits of delivering triple therapy using a single ELLIPTA dry powder inhaler (DPI) (closed triple therapy) versus delivering triple therapy using two different types of DPI (open triple therapy). The primary objective of the study is to evaluate the proportion of COPD subjects who make critical errors when using a single ELLIPTA DPI versus those using combinations of DISKUS® with HANDIHALER®, or TURBUHALER® with HANDIHALER. At Visit 1, all subjects will demonstrate the use of ELLIPTA DPI, and HANDIHALER DPI in combination with either DISKUS DPI (in sub-study 1) or TURBUHALER DPI (in sub-study 2), based on the treatment sequences. At the end Visit 1, subjects will complete the inhaler preference questionnaire (PQ). There is no active treatment and subjects will continue to take their own prescribed COPD medication for the duration of the study. ELLIPTA and DISKUS are registered trademarks of the GSK group of companies; TURBUHALER is a registered trademark of AstraZeneca and HANDIHALER is a registered trademark of Boehringer Ingelheim Pharma GmbH \& Co. KG.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. A randomized, open-label, single-visit, crossover study simulating triple-drug delivery with Ellipta compared with dual inhaler combinations in patients with COPD.
   van der Palen J, Moeskops-van Beurden W, Dawson CM, James WY, et al · · 2018 · cited 24× · PMID 30174421 · DOI 10.2147/copd.s169060
2. Critical Error Frequency and the Impact of Training with Inhalers Commonly used for Maintenance Treatment in Chronic Obstructive Pulmonary Disease.
   Collier DJ, Wielders P, van der Palen J, Heyes L, et al · · 2020 · cited 13× · PMID 32606640 · DOI 10.2147/copd.s224209
3. Correct use and ease-of-use of placebo ELLIPTA dry-powder inhaler in adult patients with chronic obstructive pulmonary disease.
   Siler TM, Jain R, Collison K, Sharma R, et al · · 2022 · cited 2× · PMID 35969632 · DOI 10.1371/journal.pone.0273170