Trial Outcomes & Findings for Study to Evaluate Handling Errors in Usage of SERETIDE® Metered Dose Inhaler (MDI) (EVOHALER®) by Adult Subjects Currently Using the SERETIDE DISKUS® Inhaler (NCT NCT02416180)

Results Overview

Participant's inhaler use was assessed on Day 14 by the health care professional (HCP) against a predefined list of critical errors (CEs). Critical errors were defined as errors that were most likely to result in no or only minimal medication being inhaled. The participants were asked to demonstrate their usage of the MDI using a placebo demonstration MDI by HCP, critical or non-critical errors (N-CEs) and even no errors made by the participants while using the MDI were recorded. Critical errors in using the MDI were defined as: failure to remove the cap; failure to shake the device; failure to place the device in mouth; no dose actuated during an inhalation manoeuvre; dose coordination that was so poor that the patient was likely to have received no dose or only received minimal dose. 95% confidence interval (CI) is for the % of participants making at least one critical error after the first assessment of the MDI technique, and was calculated using the exact binomial distribution.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

111 participants

Primary outcome timeframe

Day 14

Results posted on

2017-05-30

Participant Flow

Participants with controlled asthma who were treated with fluticasone propionate/salmeterol via DISKUS inhaler, were asked to demonstrate how they currently use their DISKUS inhaler using a demonstration inhaler. Only participants who did not make any critical errors while demonstrating the inhaler technique were considered eligible for the study.

Participant milestones

Participant milestones
Measure	Fluticasone Propionate/Salmeterol MDI Participants received fluticasone propionate/salmeterol via metered dose inhaler (MDI) for 14 days at a dose equivalent to their pre-study fluticasone propionate/salmeterol dose which was administered via DISKUS inhaler. Participants were instructed to read the fluticasone propionate/salmeterol MDI Patient Information Leaflet (PIL) and then to use the provided MDI in accordance with the PIL for approximately 14 days, in replacement of their DISKUS inhaler.
Overall Study STARTED	111
Overall Study COMPLETED	110
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Fluticasone Propionate/Salmeterol MDI Participants received fluticasone propionate/salmeterol via metered dose inhaler (MDI) for 14 days at a dose equivalent to their pre-study fluticasone propionate/salmeterol dose which was administered via DISKUS inhaler. Participants were instructed to read the fluticasone propionate/salmeterol MDI Patient Information Leaflet (PIL) and then to use the provided MDI in accordance with the PIL for approximately 14 days, in replacement of their DISKUS inhaler.
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Study to Evaluate Handling Errors in Usage of SERETIDE® Metered Dose Inhaler (MDI) (EVOHALER®) by Adult Subjects Currently Using the SERETIDE DISKUS® Inhaler

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fluticasone Propionate/Salmeterol MDI n=111 Participants Participants received fluticasone propionate/salmeterol via MDI for 14 days at a dose equivalent to their pre-study fluticasone propionate/salmeterol dose which was administered via DISKUS inhaler. Participants were instructed to read the fluticasone propionate/salmeterol MDI PIL and then to use the provided MDI in accordance with the PIL for approximately 14 days, in replacement of their DISKUS inhaler.
Age, Continuous	45.6 Years STANDARD_DEVIATION 16.76 • n=5 Participants
Sex: Female, Male Female	64 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	2 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	106 Participants n=5 Participants
Race/Ethnicity, Customized White - Mixed Race	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 14

Population: Intent to Treat (ITT) population: comprised of all participants who were screened and received at least one dose of study medication.

Participant's inhaler use was assessed on Day 14 by the health care professional (HCP) against a predefined list of critical errors (CEs). Critical errors were defined as errors that were most likely to result in no or only minimal medication being inhaled. The participants were asked to demonstrate their usage of the MDI using a placebo demonstration MDI by HCP, critical or non-critical errors (N-CEs) and even no errors made by the participants while using the MDI were recorded. Critical errors in using the MDI were defined as: failure to remove the cap; failure to shake the device; failure to place the device in mouth; no dose actuated during an inhalation manoeuvre; dose coordination that was so poor that the patient was likely to have received no dose or only received minimal dose. 95% confidence interval (CI) is for the % of participants making at least one critical error after the first assessment of the MDI technique, and was calculated using the exact binomial distribution.

Outcome measures

Outcome measures
Measure	Fluticasone Propionate/Salmeterol MDI n=111 Participants Participants received fluticasone propionate/salmeterol via MDI for 14 days at a dose equivalent to their pre-study fluticasone propionate/salmeterol dose which was administered via DISKUS inhaler. Participants were instructed to read the fluticasone propionate/salmeterol MDI PIL and then to use the provided MDI in accordance with the PIL for approximately 14 days, in replacement of their DISKUS inhaler.
Percentage of Participants Making at Least One Critical Error After the First Assessment of Metered Dose Inhaler (MDI) Technique on Day 14	14 Percentage of Participants Interval 8.0 to 21.0

SECONDARY outcome

Timeframe: Day 14

Population: ITT population

Inhaler use was assessed on Day 14 for overall errors. Overall errors included CEs or N-CEs. Demonstration of usage was with MDI and placebo, CE or N-CEs and even no errors were recorded. CEs were defined as: failure to remove the cap; failure to shake the device; failure to place the device in mouth; no dose actuated during an inhalation manoeuvre; dose coordination that was so poor that the patient was likely to have received no dose or only received minimal dose. N-CEs were defined as: failure to inhale within 5 seconds of shaking the device; no exhalation before an inhalation; the inhalation manoeuvre was not slow and/or was not deep; dose coordination was sub-optimal but patient likely to have received some dose; more than one actuation during an inhalation manoeuvre; did not hold breath. The exact 95% confidence interval is for percent of participants making at least one CE after the first assessment of the MDI technique, and was calculated using exact binomial distribution.

Outcome measures

Outcome measures
Measure	Fluticasone Propionate/Salmeterol MDI n=111 Participants Participants received fluticasone propionate/salmeterol via MDI for 14 days at a dose equivalent to their pre-study fluticasone propionate/salmeterol dose which was administered via DISKUS inhaler. Participants were instructed to read the fluticasone propionate/salmeterol MDI PIL and then to use the provided MDI in accordance with the PIL for approximately 14 days, in replacement of their DISKUS inhaler.
Percentage of Participants Making at Least One Overall Error After the First Assessment of MDI Technique on Day 14.	41 Percentage of participants Interval 31.0 to 50.0

SECONDARY outcome

Timeframe: Day 14

Population: ITT Population

Participant's inhaler use was assessed on Day 14 by the HCP against a predefined list of critical errors. If a participant made a critical error during this initial assessment, the HCP demonstrated the correct use of the inhaler to the participant and gave verbal instructions. The participant was then asked to demonstrate inhaler use. Any errors were recorded by the HCP. If the participant made a critical error then the HCP repeated the demonstration of inhaler use to the participant for a second time. If the participant continued to make a critical error in the use of the inhaler, the HCP demonstrated the correct use of the inhaler and gave verbal instructions one more time and the participant was then asked to demonstrate inhaler use. Instructions are only given to subjects who make a critical error. Any errors made after this final demonstration were recorded.

Outcome measures

Outcome measures
Measure	Fluticasone Propionate/Salmeterol MDI n=111 Participants Participants received fluticasone propionate/salmeterol via MDI for 14 days at a dose equivalent to their pre-study fluticasone propionate/salmeterol dose which was administered via DISKUS inhaler. Participants were instructed to read the fluticasone propionate/salmeterol MDI PIL and then to use the provided MDI in accordance with the PIL for approximately 14 days, in replacement of their DISKUS inhaler.
Number of Health Care Professional (HCP) Instructions Required on Day 14 2 Instructions	2 Participants
Number of Health Care Professional (HCP) Instructions Required on Day 14 0 Instruction	96 Participants
Number of Health Care Professional (HCP) Instructions Required on Day 14 1 Instruction	12 Participants
Number of Health Care Professional (HCP) Instructions Required on Day 14 3 Instructions	1 Participants

SECONDARY outcome

Timeframe: Day 14

Population: ITT Population

If a participant made a critical error during the initial assessment, the HCP demonstrated the correct use of the inhaler to the participant and gave verbal instructions. The HCP could have demonstrated the use of the inhaler a maximum of three times. Any errors made after this final demonstration were recorded. The time taken for the HCP to train the participant in the correct technique was recorded as T1: the time from when the participants started their demonstration of MDI use until they had completed their demonstration of MDI use (i.e., with no HCP support), T2: the time from when the HCP started to demonstrate/instruct device use until correct use was demonstrated by the participant (up to a maximum of three attempts only). T3 is defined as T1+T2, which is the time from when the participant started to demonstrate MDI use until correct use was demonstrated by the subject (up to a maximum of three attempts following demonstration by HCP).

Outcome measures

Outcome measures
Measure	Fluticasone Propionate/Salmeterol MDI n=111 Participants Participants received fluticasone propionate/salmeterol via MDI for 14 days at a dose equivalent to their pre-study fluticasone propionate/salmeterol dose which was administered via DISKUS inhaler. Participants were instructed to read the fluticasone propionate/salmeterol MDI PIL and then to use the provided MDI in accordance with the PIL for approximately 14 days, in replacement of their DISKUS inhaler.
Time Taken to Correctly Completing Inhaler Use at Day 14 T1, n=96	1.14 Minutes Interval 0.4 to 3.9
Time Taken to Correctly Completing Inhaler Use at Day 14 T2, n=15	3.23 Minutes Interval 1.1 to 6.2
Time Taken to Correctly Completing Inhaler Use at Day 14 T3, n=111	1.25 Minutes Interval 0.4 to 8.7

Adverse Events

Fluticasone Propionate/Salmeterol MDI

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Fluticasone Propionate/Salmeterol MDI n=111 participants at risk Participants received fluticasone propionate/salmeterol via MDI for 14 days at a dose equivalent to their pre-study fluticasone propionate/salmeterol dose which was administered via DISKUS inhaler. Participants were instructed to read the fluticasone propionate/salmeterol MDI PIL and then to use the provided MDI in accordance with the PIL for approximately 14 days, in replacement of their DISKUS inhaler.
Infections and infestations Perirectal abscess	0.90% 1/111 • Adverse events (AEs) and serious adverse events (SAE) were collected from the start of the study treatment until the follow-up contact (up to 23 days). AEs and SAEs were collected in the members of ITT Population, comprised of all participants in the treatment arm who gave informed consent and received at least one dose of study medication.

Other adverse events

Other adverse events
Measure	Fluticasone Propionate/Salmeterol MDI n=111 participants at risk Participants received fluticasone propionate/salmeterol via MDI for 14 days at a dose equivalent to their pre-study fluticasone propionate/salmeterol dose which was administered via DISKUS inhaler. Participants were instructed to read the fluticasone propionate/salmeterol MDI PIL and then to use the provided MDI in accordance with the PIL for approximately 14 days, in replacement of their DISKUS inhaler.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.90% 1/111 • Adverse events (AEs) and serious adverse events (SAE) were collected from the start of the study treatment until the follow-up contact (up to 23 days). AEs and SAEs were collected in the members of ITT Population, comprised of all participants in the treatment arm who gave informed consent and received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.90% 1/111 • Adverse events (AEs) and serious adverse events (SAE) were collected from the start of the study treatment until the follow-up contact (up to 23 days). AEs and SAEs were collected in the members of ITT Population, comprised of all participants in the treatment arm who gave informed consent and received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.90% 1/111 • Adverse events (AEs) and serious adverse events (SAE) were collected from the start of the study treatment until the follow-up contact (up to 23 days). AEs and SAEs were collected in the members of ITT Population, comprised of all participants in the treatment arm who gave informed consent and received at least one dose of study medication.
General disorders Asthenia	0.90% 1/111 • Adverse events (AEs) and serious adverse events (SAE) were collected from the start of the study treatment until the follow-up contact (up to 23 days). AEs and SAEs were collected in the members of ITT Population, comprised of all participants in the treatment arm who gave informed consent and received at least one dose of study medication.
General disorders Fatigue	0.90% 1/111 • Adverse events (AEs) and serious adverse events (SAE) were collected from the start of the study treatment until the follow-up contact (up to 23 days). AEs and SAEs were collected in the members of ITT Population, comprised of all participants in the treatment arm who gave informed consent and received at least one dose of study medication.
Infections and infestations Hand-foot-and-mouth disease	0.90% 1/111 • Adverse events (AEs) and serious adverse events (SAE) were collected from the start of the study treatment until the follow-up contact (up to 23 days). AEs and SAEs were collected in the members of ITT Population, comprised of all participants in the treatment arm who gave informed consent and received at least one dose of study medication.
Metabolism and nutrition disorders Decreased appetite	0.90% 1/111 • Adverse events (AEs) and serious adverse events (SAE) were collected from the start of the study treatment until the follow-up contact (up to 23 days). AEs and SAEs were collected in the members of ITT Population, comprised of all participants in the treatment arm who gave informed consent and received at least one dose of study medication.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

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

Restriction type: OTHER