A 24-Week Treatment Study to Compare Standard of Care Versus the eMDPI DS in Participants 13 Years or Older With Asthma

Study Overview
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Brief Summary
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The primary objective of this study is to demonstrate the effectiveness of the Digital System (DS) in improving asthma control compared to the Standard of Care (SoC) group. The secondary objective is to describe the asthma management actions by investigational center health care providers (iHCPs) for all participants in both groups, to evaluate short-acting beta2 agonist (SABA) usage and the number of SABA-free days in the DS group, to evaluate adherence patterns to maintenance treatment (FS eMDPI) in the DS group, to assess behavioral correlates of responsiveness to digital health technology among participants for all participants in both groups, to evaluate work productivity and activity impairment in asthma participants in both groups, to assess the usability and acceptability of the DS by participants in the DS group and the investigational center personnel, and to evaluate the safety of FS eMDPI and Albuterol eMDPI.

Detailed Description
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Study duration will be approximately 27 weeks including a one-week screening period, 24 week treatment period, and a 2 week follow-up period.

Official Title
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CONNected Electronic Inhalers Asthma Control Trial 2 (CONNECT 2), a 24-Week Treatment, Multicenter, Open-Label, Randomized, Parallel Group Comparison, Feasibility Study of Standard of Care Treatment Versus the eMDPI Digital System, to Optimize Outcomes in Patients at Least 13 Years of Age or Older With Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Fluticasone propionate/salmeterol (FS)
* Drug: Albuterol
* Drug: Standard of Care Asthma Medication
* Drug: Standard of Care Rescue Medication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant has a documented diagnosis of asthma established at the investigational center at the time of informed consent or the investigator confirms a diagnosis of asthma. The participant is currently on treatment with a moderate- to high-dose inhaled corticosteroid (ICS) with long-acting beta agonist (LABA). The participant has an Asthma Control Test score of less than 19 at the screening or baseline visit. The participant is willing to discontinue all other maintenance ICS with LABA medications and rescue medications and replace them with the study-provided fluticasone propionate/salmeterol (FS) multidose dry powder inhaler with integrated electronic module (eMDPI) and Albuterol eMDPI, respectively, for the duration of the trial, if randomized to the Digital System group. All other asthma maintenance medications, except for ICS with LABA, may be continued. Additional criteria apply, please contact the investigator for more information. Exclusion Criteria: The participant is currently being treated prior to enrollment with a digital inhaler system, including the Digihaler system or an external bolt on digital system designed to monitor inhaler usage, such as the Propeller Health or Adherium systems. The participant has any clinically significant uncontrolled medical condition (treated or untreated) other than asthma, which in the view of the investigator would preclude participation. The participant was hospitalized for severe asthma in the last 30 days. The participant has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the patient's ability to participate in this study. Additional criteria apply, please contact the investigator for more information.

Ages Eligible for Study
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Minimum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Digital System (DS)<br>DS group participants utilizing the eMDPI DS, including inhaler, smart device application (App), DHP (Cloud solution), and dashboard | Drug: Fluticasone propionate/salmeterol (FS)<br>* FS administered via electronic multidose dry powder inhaler (eMDPI) Digital System (DS) with component devices including smart device application (App), Digital Health Platform (DHP), and provider-facing dashboard<br>Drug: Albuterol<br>* Albuterol administered via electronic multidose dry powder inhaler (eMDPI) Digital System (DS) with component devices including smart device application (App), Digital Health Platform (DHP), and provider-facing dashboard<br>|
| Active Comparator: Standard of Care (SoC) Group<br>SoC group participants will be treated with their standard of care medications | Drug: Standard of Care Asthma Medication<br>* Current inhaled corticosteroid(ICS)/Long-acting beta agonist(LABA) and any additional controller medication for asthma<br>Drug: Standard of Care Rescue Medication<br>* Current rescue medication<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving Well-Controlled Asthma or Reaching Clinically Important Improvement in Asthma Control | A well-controlled asthma was defined as an Asthma Control Test (ACT) score of greater than or equal to 20. Clinically important improvement in asthma control was defined by an increase of at least 3 ACT units from baseline. The ACT was a simple, participant-completed tool used for the assessment of overall asthma control. The ACT included 5 items that assessed daytime and nighttime asthma symptoms, use of reliever medication, and impact of asthma on daily functioning. Each item in the ACT was scored on a 5-point scale ranging from 1 (poor control of asthma) to 5 (well control of asthma), with summation of all items providing scores ranging from 5 to 25. The scores span the continuum of poor control of asthma (score of 5) to complete control of asthma (score of 25), with a cutoff score of 19 and below indicating participants with poorly controlled asthma. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Discussions Between Participant and Investigational Center Healthcare Professional (iHCP) Regarding Inhaler Technique or Adherence | Number of participants who had discussions with iHCP regarding inhaler technique or adherence are reported. | Baseline up to Week 24 | 
| Number of Decreased Doses of Inhaled Medication | Number of participants who received decreased dose of inhaled medication during the 24-week treatment period are reported. | Baseline up to Week 24 | 
| Number of Increased Doses of Inhaled Medication | Number of participants who received increased dose of inhaled medication during the 24-week treatment period are reported. | Baseline up to Week 24 | 
| Number of Changes to Different Inhaled Medication | Number of participants who received different inhaled medication during the 24-week treatment period are reported. | Baseline up to Week 24 | 
| Number of Additional Inhaled Medication | Number of participants who received additional inhaled medication during the 24-week treatment period are reported. | Baseline up to Week 24 | 
| Number of Addition of a Systemic Corticosteroid Medication for Asthma Therapy | Number of participants who received additional systemic corticosteroid medication for asthma therapy during the 24-week treatment period are reported. | Baseline up to Week 24 | 
| Frequency of Intervention to Manage Comorbid Conditions Associated With Poor Asthma Control | Number of participants with different frequency of intervention to manage comorbid conditions such as Gastroesophageal Reflux Disease (GERD) and Sinusitis are reported. | Baseline up to Week 24 | 
| Change From Baseline in Mean Weekly SABA Usage at Week 24 for the DS Group |  | Baseline, Week 24 | 
| Change From Baseline in the Number of SABA-free Days at Week 24 for the DS Group | Number of days a participant did not use the rescue medication in a week are reported. | Baseline, Week 24 | 
| Change From Baseline in Adherence to Maintenance Treatment (FS eMDPI) at Week 24 for the DS Group | Adherence to maintenance treatment was defined as the percentage of actual inhalation doses taken out of the total number of inhalation doses prescribed over the 24- week treatment period. | Baseline, Week 24 | 
| Change From Baseline in Beliefs About Medicines Questionnaire (BMQ) Concern Subscale Score at Week 24 | The BMQ was used to assess cognitive representations of medicine. The Beliefs About Medicines Questionnaire-Specific 11 (BMQ-S11) was an 11-item questionnaire that assessed the representation of medication prescribed for personal use and the BMQ-General assesses beliefs about medicines in general. BMQ concern is a 6-item scale assessing participant's concerns about potential adverse consequences (range: 1=strongly disagree to 5=strongly agree). Participants indicated their degree of agreement on a 5-point scale, ranging from 1=strongly disagree to 5=strongly agree. Scores obtained for individual items were summed, divided by the total number of items and multiplied by 5 to give a total score ranging from 5 to 25 (higher scores=stronger beliefs). | Baseline, Week 24 | 
| Change From Baseline in BMQ Necessity Subscale Score at Week 24 | The BMQ was used to assess cognitive representations of medicine. The Beliefs About Medicines Questionnaire-Specific 11 (BMQ-S11) was an 11-item questionnaire that assessed the representation of medication prescribed for personal use and the BMQ-General assesses beliefs about medicines in general. BMQ necessity is a 5-item scale assessing participant's beliefs about necessity of medications for controlling disease. Participants indicated degree of agreement on a 5-point scale, ranging from 1=strongly disagree to 5=strongly agree. Scores obtained for individual items were summed, divided by the total number of items and multiplied by 5 to give a total score ranging from 5 to 25 (higher scores=stronger beliefs). | Baseline, Week 24 | 
| Change From Baseline in Brief Illness Perception Questionnaire (BIPQ) Illness Comprehensibility Subscale Score at Week 24 | The BIPQ was a 9-item questionnaire designed to rapidly assess cognitive and emotional representations of illness. Only one item assesses illness comprehensibility or coherence of illness (Item 7: How well do you feel you understand your illness?). This item was rated using a 0 (do not understand at all) to 10 (understand very clearly) response scale. A higher score indicates a stronger illness comprehensibility. | Baseline, Week 24 | 
| Change From Baseline in BIPQ Cognitive Subscale Score at Week 24 | BIPQ was a 9-item questionnaire designed to rapidly assess cognitive and emotional representations of illness. It comprised 5 items on cognitive representation of illness perception: consequences (Item 1: How much does your illness affect your life? Response range 0 [no affect] - 10 [severe affect]), timeline (Item 2: How long do you think your illness will continue? Response range 0 [a very short time] - 10 [forever]), personal control (Item 3: How much control do you feel you have over your illness? Response range 0 [no control] - 10 [extreme amount of control]), treatment control (Item 4: How much do you think your treatment can help your illness? Response range 0 [not at all] - 10 [extremely helpful]), and identity (Item 5: How much do you experience symptoms from your illness? Response range 0 [no symptoms] - 10 [severe symptoms]). Total BIPQ Cognitive Subscale Score was the sum of all item score and ranged from 0 to 50. A higher score indicates stronger illness perception. | Baseline, Week 24 | 
| Change From Baseline in BIPQ Emotional Representations Subscale Score at Week 24 | BIPQ was a 9-item questionnaire designed to rapidly assess cognitive and emotional representations of illness. It comprised 2 items on emotional representation: concern (Item 6: How concerned are you about your illness? Response range 0 [not at all concerned] - 10 [extremely concerned]) and emotions (Item 8: How much does your illness affect you emotionally; for example, does it make you angry, scared, upset or depressed? Response range 0 [not at all affected emotionally] - 10 [extremely affected emotionally]). Total BIPQ Emotional Subscale Score was the sum of above 2 items score and ranged from 0 to 20. A higher score indicates extreme emotional representation. | Baseline, Week 24 | 
| Change From Baseline in Work Productivity and Activity Impairment (WPAI) Asthma Questionnaire Score at Week 24 | WPAI-asthma is a self-administered instrument to measure asthma-specific performance impairment of work and regular daily activity within the last 7 days and yields 4 types of scores: work time missed (absenteeism), impairment while working (presenteeism or reduced on-the-job effectiveness), overall work impairment (WI) (work productivity loss or absenteeism plus presenteeism) and activity impairment (daily activity impairment). Total score and each score ranged from 0 (not affected/no impairment) to 100 (completely affected/impaired). Higher scores indicated greater impairment and less productivity. | Baseline, Week 24 | 
| System Usability Scale (SUS) Overall Score for DS Group | The SUS was used to explore device acceptability and usability for participants in the DS group. It covered a variety of aspects of system usability, such as the need for support, training, and complexity, and thus giving a global view of subjective assessments of usability. It was a 10-question tool (with five response options; from 1=strongly disagree to 5=strongly agree) that provided a composite measure, ranging from 0 to 100, of the overall usability of the system being studied. Higher scores represent better usability level for the tool. | Week 24 | 
| Number of Participants With Adverse Events (AEs) | An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'. Number of participants with any AEs, and device-related AEs has been reported. | Baseline up to Week 26 |