A Randomized Study to Evaluate the Effect of Reminder Notifications and Motivational/Adaptive Messaging on Treatment Adherence

Study Overview
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Brief Summary
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This study was evaluating the effect of reminder notifications and motivational/adaptive messages on treatment adherence behavior in subjects with COPD. The effect will be measured over 24 weeks on the subject's on time treatment adherence and total treatment adherence. The delivery of the medication and tracking of inhaler use is done by the Concept2 inhaler. The reminder notification, feedback on inhaler use and motivational messages are provided by the patient application, who is receiving the inhaler use information from the Concept2 inhaler.

Detailed Description
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This study was evaluating whether subjects with COPD on Ultibro® Breezhaler® clinical trial formulation once daily dosing regimen using the Concept2 inhaler in conjunction with a patient application collecting data and sending reminder notifications and motivational/adaptive messages aimed at encouraging treatment adherence, have improved treatment adherence compared to subjects using the Concept2 inhaler alone (usual care). The delivery of the medication and tracking of inhaler use is done by the Concept2 inhaler. The reminder notifications, feedback on inhaler use and motivational messages for the subject are sent by the patient application based on the received subjects inhaler use information from the Concept2 inhaler. The effect will be measured over 24 weeks on the subject's on time treatment adherence (days when the subjects inhaled within +/- 2 hours of the subjects preferred inhalation time) and total treatment adherence (days when patient inhaled at least one dose). The study population consisted male and female adult patients, 18 years or older with a clinical diagnosis of COPD, a smoking history of 10 pack years, receiving Ultibro Breezhaler treatment for at least 3 months prior to screening and documented poor treatment adherence. After 6 weeks of screening patients will be randomized to either the Usual Care group in which they will continue to receive Ultibro Breezhaler treatment via the Concept2, or the Telehealth group in which they will additionally receive a tablet device pre-installed with a patient app. In addition to on time treatment adherence and total treatment adherence, illness and treatment beliefs will be collected via a questionnaire and patient's health status from the EQ5D-5L and SGRQ-C Questionnaire. Key safety assessments are COPD exacerbation and AE/SAE, device deficiencies and device events, drug administration errors, physical exam, vital signs and urine or serum pregnancy test.

Official Title
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A 24-week Randomized, Controlled, Multicenter, Open-label Study to Evaluate the Effect of Reminder Notifications and Motivational/Adaptive Messaging on Treatment Adherence of COPD Subjects Receiving Ultibro® Breezhaler® Treatment Using the Concept2 Inhaler for Dose Administration and Tracking

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Combination Product: Concept2 inhaler
* Combination Product: Concept2 inhaler with patient application


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Have a total adherence of more than 10% but less than or equal to 70% during Screening period Current or ex-smokers who have a smoking history of at least 10 pack years. A diagnosed COPD Taking Ultibro® Breezhaler® for at least 3 month prior to Visit 1 Have been in the Screening period ≥ 35 days. Exclusion Criteria: Pregnant or lactating women Women of child-bearing potential Subjects having a history of reactions/hypersensitivity to inhaled drugs or drugs of a similar class Subjects having a history of reactions/hypersensitivity to lactose or any of the other ingredients of trial medication. Subjects with relevant concomitant diseases Subjects who have had a COPD exacerbation 6 weeks prior to Visit 1 or between V1 and randomization Subjects who have had a respiratory tract infection within 3 weeks prior to Visit 1 or between V1 and randomization Use of investigational drugs or other investigational devices at the time of enrollment Subjects with a preferred inhalation time between 10.00 pm and 2.00 am. Subjects taken off Ultibro® Breezhaler® treatment/inhaler use by the investigator during the Screening period for more than 7 days. Subjects not returning all Concept2 inhalers received during the Screening period Subjects who have demonstrated inability or unwillingness to use the digital system or to fill in questionnaires. Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 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: Device Feasibility
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Usual Care<br>Concept2 inhaler | Combination Product: Concept2 inhaler<br>* Fixed combination of Indacaterol maleate (QAB149) and glycopyrronium bromide (NVA237), 110/50 μg, capsule added to Concept2 inhaler<br>|
| Experimental: Telehealth<br>Concept2 inhaler with patient application | Combination Product: Concept2 inhaler with patient application<br>* Fixed combination of Indacaterol maleate (QAB149) and glycopyrronium bromide (NVA237), 110/50 μg, capsule added to Concept2 inhaler with application used for monitoring<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Participant's On-time Adherence Over 24 Weeks of Intervention Compared to Baseline | On-time treatment adherence was defined as percentage of days on which the participant inhaled at least one dose on-time. Dose inhaled on-time was a dose inhaled within (+ or -) 2 hours of the agreed predefined preferred daily inhalation time (PIT). PIT was defined by the participant at study start. | Baseline 6 weeks, intervention 24 weeks | 
| Change in Participant's Total Adherence Over 24 Weeks of Intervention Compared to Baseline | Total adherence was defined as percentage of days on which the participant inhaled at least one dose and represented the sum of on-time adherence and off-time adherence. Off-time adherence was defined as percentage of days on which the participant did not inhale the daily dose within the (+ or -) 2 hours of the predefined PIT, but outside. The number of doses not inhaled on-time was recorded by the Concept2 inhaler. | Baseline 6 weeks, intervention 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Participant's 6 Weeks Baseline On-time Adherence to the Participant's On-time Adherence Over the Last Four Weeks of Intervention | On-time treatment adherence was defined as percentage of days on which the participant inhaled at least one dose on-time. Dose inhaled on-time was a dose inhaled within (+ or -) 2 hours of the agreed predefined preferred daily inhalation time (PIT). PIT was defined by the participant at study start. | Baseline, Week 21 - 24 | 
| Change From Participant's 6 Weeks Baseline Total Adherence to the Participant's Total Adherence Over the Last Four Weeks of Intervention | Total adherence was defined as percentage of days on which the participant inhaled at least one dose and represented the sum of on-time adherence and off-time adherence. Off-time adherence was defined as percentage of days on which the participant did not inhale the daily dose within the (+ or -) 2 hours of the predefined PIT, but outside. The number of doses not inhaled on-time was recorded by the Concept2 inhaler. | Baseline, Week 21 - 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease, Adherence, Dose Tracking, Concept2, Digital Adherence System, Ultibro Breezhaler