Study to Evaluate the Mastery of Inhaler Technique for Budesonide Formoterol (BF) SPIROMAX® as Compared to SYMBICORT® TURBOHALER® as Treatment for Adult Participants With Asthma (ELIOT)

A 12-Week, Randomized, Open-Label, Parallel-Group Study to Evaluate the Mastery of Inhaler Technique for Budesonide Formoterol (BF) SPIROMAX® (160/4.5 and 320/9 mcg) as Compared With SYMBICORT® TURBOHALER® (200/6 and 400/12 mcg) as Treatment for Adult Patients With Asthma (The Easy Low Instruction Over Time [ELIOT] Study)

This study is conducted to assess whether training participants on proper use of BF SPIROMAX and Symbicort TURBOHALER will improve their device-handling technique and potentially improve their treatment outcome, that is, better asthma control.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Budesonide and formoterol fumarate dehydrate (BF) SPIROMAX; Drug: SYMBICORT TURBOHALER budesonide and formoterol fumarate

• Study Type: Interventional
• Enrollment (Actual): 485
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Axbridge, United Kingdom, BS26 2BJ
    • Teva Investigational Site 34092
  • Babbacombe, United Kingdom, TQ1 3SL
    • Teva Investigational Site 34081
  • Beccles, United Kingdom, NR34 9NX
    • Teva Investigational Site 34103
  • Bishops Stortford, United Kingdom, CM22 7EH
    • Teva Investigational Site 34144
  • Burnhope, United Kingdom, DH7 0BD
    • Teva Investigational Site 34066
  • Bury St Edmunds, United Kingdom, IP30 9QU
    • Teva Investigational Site 34064
  • Bury St Edmunds, United Kingdom, IP32 7EW
    • Teva Investigational Site 34107
  • Cheltenham, United Kingdom, GL50 4DP
    • Teva Investigational Site 34072
  • Chippenham, United Kingdom, SN14 6GT
    • Teva Investigational Site 34063
  • Chipping Norton, United Kingdom, OX7 6BW
    • Teva Investigational Site 34122
  • Clacton-on-Sea, United Kingdom, CO15 4DA
    • Teva Investigational Site 34134
  • Colchester, United Kingdom, CO1 2DL
    • Teva Investigational Site 34136
  • Colchester, United Kingdom, CO1 2QS
    • Teva Investigational Site 34143
  • Colchester, United Kingdom, CO2 7GH
    • Teva Investigational Site 34111
  • Colchester, United Kingdom, CO3 4RA
    • Teva Investigational Site 34126
  • Colchester, United Kingdom, CO3 4RY
    • Teva Investigational Site 34135
  • Colchester, United Kingdom, CO7 9PP
    • Teva Investigational Site 34120
  • Daventry, United Kingdom, NN11 4DY
    • Teva Investigational Site 34075
  • Daventry, United Kingdom, NN11 5RA
    • Teva Investigational Site 34112
  • East Hunsbury, United Kingdom, NN4 0NY
    • Teva Investigational Site 34083
  • East Tillbury, United Kingdom, RM18 8SD
    • Teva Investigational Site 34145
  • Exmouth, United Kingdom, EX8 2JF
    • Teva Investigational Site 34099
  • Exmouth, United Kingdom, EX8 2JF
    • Teva Investigational Site 34110
  • Goldhay, United Kingdom, PE2 5GP
    • Teva Investigational Site 34102
  • Great Yarmouth, United Kingdom, NR31 0DW
    • Teva Investigational Site 34119
  • Harrogate, United Kingdom, HG1 5AR
    • Teva Investigational Site 34079
  • Harrogate, United Kingdom, HG1 5JP
    • Teva Investigational Site 34068
  • Hemel Henpstead, United Kingdom, HP1 2LD
    • Teva Investigational Site 34139
  • Hinckley, United Kingdom, LE10 1DS
    • Teva Investigational Site 34142
  • Huntingdon, United Kingdom, PE28 4EQ
    • Teva Investigational Site 34116
  • Ipswich, United Kingdom, IP1 6DW
    • Teva Investigational Site 34113
  • Lancashire, United Kingdom, FY4 3AD
    • Teva Investigational Site 34098
  • Leicester, United Kingdom, LE2 6UL
    • Teva Investigational Site 34128
  • Leicester, United Kingdom, LE5 4BP
    • Teva Investigational Site 34127
  • Leigh-on-Sea, United Kingdom, SS9 2SQ
    • Teva Investigational Site 34141
  • Liskeard, United Kingdom, PL14 3XA
    • Teva Investigational Site 34082
  • Lister House, United Kingdom, CM18 7LU
    • Teva Investigational Site 34146
  • Liverpool, United Kingdom, L36 0UB
    • Teva Investigational Site 34147
  • Loughborough, United Kingdom, LE11 1NH
    • Teva Investigational Site 34080
  • Lowestoft, United Kingdom, NR33 8LG
    • Teva Investigational Site 34086
  • Luton, United Kingdom, PU2 9SB
    • Teva Investigational Site 34138
  • Manchester, United Kingdom, OL9 0LH
    • Teva Investigational Site 34076
  • Newton Aycliffe, United Kingdom, DL5 4SE
    • Teva Investigational Site 34109
  • Norwich, United Kingdom, NR11 6AA
    • Teva Investigational Site 34095
  • Norwich, United Kingdom, NR12 8DU
    • Teva Investigational Site 34108
  • Norwich, United Kingdom, NR5 0GB
    • Teva Investigational Site 34091
  • Norwich, United Kingdom, NR5 9HA
    • Teva Investigational Site 34123
  • Norwich', United Kingdom, NR3 2HW
    • Teva Investigational Site 34106
  • Oadby, United Kingdom, LE2 4PE
    • Teva Investigational Site 34085
  • Oldham, United Kingdom, OL9 8NH
    • Teva Investigational Site 34070
  • Orby, United Kingdom, NN17 1QP
    • Teva Investigational Site 34114
  • Oxon, United Kingdom, OX33 1YJ
    • Teva Investigational Site 34118
  • Pickering, United Kingdom, YO18 8BL
    • Teva Investigational Site 34137
  • Reading, United Kingdom, RG8 7DP
    • Teva Investigational Site 34124
  • Redditch, United Kingdom, B98 0NR
    • Teva Investigational Site 34089
  • Sheringham, United Kingdom, NR26 8RT
    • Teva Investigational Site 34100
  • Stalham, United Kingdom, NR12 9BU
    • Teva Investigational Site 34117
  • Stanley, United Kingdom, DH9 7TD
    • Teva Investigational Site 34105
  • Stowmarket, United Kingdom, IP14 1NL
    • Teva Investigational Site 34065
  • Strensall, United Kingdom, YO32 5UA
    • Teva Investigational Site 34067
  • Swindon, United Kingdom, SN2 1UU
    • Teva Investigational Site 34078
  • Thaxted, United Kingdom, CM6 2QN
    • Teva Investigational Site 34140
  • Thornton-Cleveleys, United Kingdom, FY5 2TZ
    • Teva Investigational Site 34096
  • Trowbridge, United Kingdom, BA14 8QA
    • Teva Investigational Site 34088
  • Trowbridge, United Kingdom, BA14 9AR
    • Teva Investigational Site 34077
  • Waterlooville, United Kingdom, PO7 5XP
    • Teva Investigational Site 34071
  • Waterlooville, United Kingdom, PO7 7AH
    • Teva Investigational Site 34073
  • Wells-Next-Sea, United Kingdom, NR23 1JP
    • Teva Investigational Site 34084
  • Wisbech, United Kingdom, PE14 7RR
    • Teva Investigational Site 34115
  • Woodbridge, United Kingdom, IP12 3DA
    • Teva Investigational Site 34069
  • Woodbridge, United Kingdom, IP12 4FD
    • Teva Investigational Site 34074
  • Worcester, United Kingdom, WR1 2BS
    • Teva Investigational Site 34090
  • Wymondham, United Kingdom, NR18 0RF
    • Teva Investigational Site 34121
  • York, United Kingdom, YO24 4HD
    • Teva Investigational Site 34101

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The participant has a diagnosis of asthma in accordance with Global Initiative for Asthma (GINA) criteria as evidenced by a United Kingdom (UK) quality outcome framework approved Read code (UK diagnostic coding system).
• The participant is receiving step 3 or 4 therapy for asthma as defined by the British Thoracic Society (BTS) guidelines (daily doses of beclomethasone dipropionate [BDP]-equivalent ICS) ≥800 mcg to 2000 μg as part of fixed- or free combinations with long-acting β2-agonists (LABA).
• If participant is a female of childbearing potential (post-menarche or less than 2 years post-menopausal or not surgically sterile), the participant must be willing to commit to using a medically accepted method of contraception for the duration of study and 30 days after discontinuing study drug.
• The participant, as judged by the investigator, must be willing and able to understand risks and benefits of study participation to give informed consent and to comply with all study requirements as specified in this protocol for the entire duration of their study participation.
• The participant is SPIROMAX and TURBOHALER naïve (no use of a SYMBICORT TURBOHALER device in the last 6 months, minimizing carryover from prior device use).

• If female and of childbearing potential, the participant must have a negative urine pregnancy test.

  • other criteria apply, please contact the investigator for additional information.

Exclusion Criteria:

• The participant has any clinically significant uncontrolled medical condition (treated or untreated) that, in the judgment of the investigator, will cause participation in the study to be detrimental to the participant.
• The participant has participated in a Teva-sponsored clinical study with BF SPIROMAX in the last 6 months.
• The participant is a pregnant, attempting to become pregnant, or breast feeding. (Any woman becoming pregnant during the study will be withdrawn from the study.)
• The participant has used a clinical trial investigational drug within 1 month before the screening visit.
• The participant has an ongoing asthma exacerbation or has received OCS and/or antibiotics for a lower respiratory condition (proxy measure for identifying an asthma exacerbation and/or lower respiratory infection, suggestive of altered inspiratory capabilities) in the 2 weeks preceding visit 1.
• The participant is currently receiving any OCS (including long or short courses).
• The participant has a significant chronic lower respiratory tract disease other than asthma (for example chronic obstructive pulmonary disease [COPD], cystic fibrosis or interstitial lung disease). Conditions that are not predominant, such as minor degrees of bronchiectasis, are not a reason for exclusion.

• The participant has a known allergy or severe sensitivity to the constituents of the study drugs (SPIROMAX or TURBOHALER),for example, to lactose or to milk protein.

  • other criteria apply, please contact the investigator for additional information.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Stage 1: Empty Spiromax Followed by Empty Turbohaler; Participants will be trained on the proper use of empty Spiromax followed by empty Turbohaler devices.
No Intervention: Stage 1: Empty Turbohaler Followed by Empty Spiromax; Participants will be trained on the proper use of empty Turbohaler followed by empty Spiromax devices.
Experimental: Stage 2: BF Spiromax; Participants who have currently received 800 to 1000 micrograms (μg) beclomethasone-equivalent inhaled corticosteroid (ICS) per day will receive budesonide/formoterol twice daily using the BF Spiromax 160/4.5 device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using BF Spiromax will be 640 μg and 18 μg, respectively. Participants who have currently received 1600 to 2000 μg beclomethasone-equivalent ICS per day will receive budesonide/formoterol twice daily using the BF Spiromax 320/9 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using BF Spiromax will be 1280 μg and 36 μg, respectively.	Drug: Budesonide and formoterol fumarate dehydrate (BF) SPIROMAX; SPIROMAX (BF) Budesonide and formoterol fumarate dehydrate (160/4.5 and 320/9 μg); Other Names: SPIROMAX®
Active Comparator: Stage 2: Symbicort Turbohaler; Participants who have currently received 800 to 1000 μg beclomethasone-equivalent ICS per day will receive budesonide/formoterol twice daily using the Symbicort Turbohaler 200/6 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using Symbicort Turbohaler will be 800 μg and 24 μg respectively. Participants who have currently received 1600 to 2000 μg beclomethasone-equivalent ICS per day will receive budesonide/formoterol twice daily using the Symbicort Turbohaler 400/12 μg device. Therefore, the daily, ex-mouthpiece doses of budesonide and formoterol using Symbicort Turbohaler will be 1600 μg and 48 μg respectively.	Drug: SYMBICORT TURBOHALER budesonide and formoterol fumarate; SYMBICORT® TURBOHALER® (200/6 and 400/12 μg); Other Names: SYMBICORT®; TURBOHALER®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1: Percentage of Participants Achieving Device Mastery	Device mastery was defined as absence of healthcare professional (HCP)-observed errors by the end of Step 3 of a 6-step standardized device training protocol for empty Spiromax compared to empty Turbohaler. The 6 steps of device training protocol were: Step 1 - Intuitive use; Step 2 - Patient information leaflet; Step 3 - Instructional video; Step 4 - HCP tuition; Step 5 - HCP tuition (1st repeat); Step 6 - HCP tuition (2nd repeat).	Baseline (Day 1)
Stage 2: Percentage of Participants Maintaining Device Mastery	Maintenance of device mastery was defined as absence of HCP-observed errors after 12 weeks of device use.	Baseline up to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1: Number of Nurse-Observed Errors		Day 1
Stage 2: Number of Technology-Observed Errors (Vitalograph Pneumotrac Spirometer)		Week 12
Stage 1: Percentage of Participants Achieving Device Mastery by Step 1	The number of participants achieving device mastery by Step 1 (no training/intuitive use) of the device training process. Device mastery was defined as the absence of nurse-observed errors by the end of Step 3 of a 6-step standardized device training protocol for each device. The 6 training steps were as follows: Step 1, intuitive use; Step 2, patient device information leaflet; Step 3, instructional video; Step 4, nurse tuition; Step 5, nurse tuition (1st repeat); Step 6, nurse tuition (2nd repeat). After each training step an assessment of device use was carried out by the nurse using a pre-defined list of inhaler errors.	Day 1
Stage 1: Percentage of Participants Achieving Device Mastery by Step 2	The number of participants achieving device mastery by Step 2 (patient device information leaflet) of the device training process. Device mastery was defined as the absence of nurse-observed errors by the end of Step 3 of a 6-step standardized device training protocol for each device. The 6 training steps were as follows: Step 1, intuitive use; Step 2, patient device information leaflet; Step 3, instructional video; Step 4, nurse tuition; Step 5, nurse tuition (1st repeat); Step 6, nurse tuition (2nd repeat). After each training step an assessment of device use was carried out by the nurse using a pre-defined list of inhaler errors.	Day 1
Stage 1: Number of Steps Taken to Achieve Device Mastery		Baseline (Day 1)
Stage 1: Patient Satisfaction and Preference Questionnaire (PASAPQ) Total Score	The PASAPQ is a multi-item measure of inhalation device satisfaction and preference designed specifically for participants with asthma and chronic obstructive pulmonary disease. The PASAPQ includes a total of 14 device satisfaction items, including an overall satisfaction item. The total score was the sum of the 13 items related to performance and convenience domains (7 items for performance domain: Questions 1-5, 10-11, and 6 items for convenience domain: Questions 6-9, 12-13). Each PASAPQ item had response options ranging from 1 (very dissatisfied) to 7 (very satisfied). To calculate the total score, the items within each domain were first summed and then transformed to a 0 (least) or 100 (most) point scale, with higher scores indicating greater satisfaction.	Baseline (Day 1)
Composite Endpoint: Stage 2: Total Number of Observed Errors (Nurse and Technology [Vitalograph Pneumotrac Spirometer])	Composite score calculated as the sum of nurse observed errors and technology-observed errors.	Baseline up to Week 12
Stage 2: Total Number of Handling Errors	Total number of device handling errors included HCP observed errors and technology observed errors.	Baseline up to Week 12
Stage 2: Change in Handling Errors From Stage 1 to Stage 2	The difference in the number of handling errors identified after participant training using the patient device information leaflet at stage 1 and after 12 weeks of treatment (end of stage 2).	Baseline (Day 1), Week 12
Stage 2: Number of Participants In Pre-specified Treatment Adherence Categories (Assessed by Device Dose Counters)	Treatment adherence was categorized (as less than or equal to 50%, 51%-70%, 71%-99%, and 100%) and compared across treatment groups using a chi-square test.	Baseline up to Week 12
Stage 2: Change From Baseline in 6-Item Asthma Control Questionnaire (ACQ) (Excluding Forced Expiratory Volume in 1 Second [FEV1] Question) Score at Weeks 4, 8, and 12	The ACQ is a 7-item, validated tool for assessing asthma control (Juniper et al 1999). Thinking about their asthma for the last 7 days, participants were asked to evaluate their asthma against 5 symptom items and a rescue bronchodilator use question using a 7-point scale (0=no impairment and 6=maximum impairment). Spirometry data were used to grade the percent predicted forced expiratory volume in 1 second (FEV1) on a 7-point scale (0 to 6). The score is the mean of the first 6 questions (excluding the FEV1 question), generating a value from 0 (totally controlled) to 6 (severely uncontrolled). A negative change from Baseline indicates improvement.	Baseline, Weeks 4, 8, and 12
Stage 2: Change From Baseline in 7-Item ACQ	The ACQ is a 7-item, validated tool for assessing asthma control (Juniper et al 1999). Thinking about their asthma for the last 7 days, participants were asked to evaluate their asthma against 5 symptom items and a rescue bronchodilator use question using a 7-point scale (0=no impairment and 6=maximum impairment). Spirometry data were used to grade the percent predicted FEV1 on a 7-point scale (0 to 6). The ACQ score is the mean of the 7 questions, generating a value from 0 (totally controlled) to 6 (severely uncontrolled). A negative change from Baseline indicates improvement.	Baseline, Week 12
Stage 2: Time to First Treatment Failure	Time to treatment failure was defined as change of asthma treatment or treatment for an asthma exacerbation or lower respiratory tract infection.	Baseline up to Week 12
Stage 2: Number of Participants With Severe Asthma Exacerbations	Severe asthma exacerbation was defined as a hospitalization or emergency room attendance for asthma, or an acute course of oral corticosteroids (OCS).	Week 12
Stage 2: Impact of Maintaining Device Mastery on Time to Treatment Failure	The impact of maintaining device mastery on time to treatment failure (defined as change of asthma treatment or treatment for an asthma exacerbation or lower respiratory tract infection) was assessed by comparing the time to treatment failure for participants with and without device mastery. Device mastery was defined as the absence of nurse-observed errors by the end of Step 3 of a 6-step standardized device training protocol for each device.	Baseline Up to Week 12
Stage 2: Impact of Maintaining Device Mastery on Asthma Control Questionnaire Score	The impact of maintaining device mastery on asthma control was assessed by comparing the 7-item ACQ scores for participants with and without device mastery. The ACQ is a 7-item, validated tool for assessing asthma control (Juniper et al 1999). Thinking about their asthma for the last 7 days, participants were asked to evaluate their asthma against 5 symptom items and a rescue bronchodilator use question using a 7-point scale (0=no impairment and 6=maximum impairment). Spirometry data were used to grade the percent predicted FEV1 on a 7-point scale (0 to 6). The ACQ score is the mean of the 7 questions, generating a value from 0 (totally controlled) to 6 (severely uncontrolled). Device mastery was defined as the absence of nurse-observed errors by the end of Step 3 of a 6-step standardized device training protocol for each device.	Baseline Up to Week 12
Number of Participants With Adverse Events (AEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.	Baseline up to Week 12

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Investigators: Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2014
• Primary Completion (Actual): March 13, 2015
• Study Completion (Actual): March 13, 2015

Study Registration Dates

• First Submitted: February 12, 2014
• First Submitted That Met QC Criteria: February 12, 2014
• First Posted (Estimated): February 13, 2014

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: September 7, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Budesonide; Formoterol Fumarate; Budesonide, Formoterol Fumarate Drug Combination
• Other Study ID Numbers: BFS-AS-40035; 2013-004630-14 (EudraCT Number)