Peak Inspiratory Flow and Dry Powder Inhaler Performance in COPD

Study Overview
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Brief Summary
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The purpose of the study is to determine whether PIF is clinically important when using the Ellipta DPI device. In addition, the study will validate the best/most clinically appropriate way to perform a PIF maneuver, to determine the testing capabilities of the preferred PIF maneuver and to relate this PIF measurement to meaningful clinical outcomes in COPD patients

Detailed Description
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Study Design and Methods Rationale The expected FEV1 response to a bronchodilator is uncertain as multiple factors influence this measure, including severity of disease, day to day variability, varying reversibility in COPD patients, the delivery of the drug to a patient and the effectiveness of the medication delivered. Thus, the measurement of an acute bronchodilator response after delivering a long acting bronchodilator may not identify whether a medication has been effectively delivered to a patient. However, if a long acting bronchodilator has not been effectively delivered to the lung, then subsequent delivery of a short acting bronchodilator should produce a significant additional bronchodilator response. On the other hand, if a long acting bronchodilator has been effectively delivered to the lung, then subsequent delivery of a short acting bronchodilator should not produce any further significant bronchodilation. Based on this rationale, comparison of the acute bronchodilator response to a short acting bronchodilator after receiving a long acting should identify whether drug delivery is ineffective in a selected patient population, irrespective of baseline FEV1 and of any partial response to the long acting bronchodilator. Comparison of the short acting bronchodilator measurement between patient groups with differing PIF thresholds should identify whether PIF has an impact of drug delivery of a long acting bronchodilator via a DPI. Open label design comparing the acute bronchodilator response after delivery of a long acting bronchodilator via Ellipta DPI in patients with normal, suboptimal and minimal PIF.

Official Title
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Peak Inspiratory Flow (PIF) and Dry Powder Inhaler (DPI) Performance in Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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COPD

Intervention / Treatment
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* Drug: Trelegy Ellipta 100/62.5/25Mcg Inh 30D
* Drug: Ventolin 90Mcg/Actuation Inhalation Aerosol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: smoking history >10 pack years pre-bronchodilator FEV1 <60% predicted post-bronchodilator FEV1/FVC <70% female participants are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential OR agree to follow the contraceptive guidance during the treatment period and until the safety follow-up contact after the last dose of study treatment stratification requiring at least 1/3 of patients having a PIF of < 60L/min (AM pre-dose based on using the level 2 InCheck Dial resistance setting with a sharp maximal effort starting after exhaling fully) Exclusion Criteria: any subject with unstable disease, including COPD exacerbation in the last 6 weeks upper respiratory tract in in the last 4 weeks COPD or upper respiratory tract infection during run-in (subjects may be re-screened x 1 when stable after an acute event) pulmonary disease other than COPD any lung resection unstable cardiac conditions (at the discretion of the investigator) other unstable medical conditions (at the discretion of the investigator)

Ages Eligible for Study
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Minimum Age: 40 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
Intervention Model: Single Group Assignment
Interventional Model Description: Open label comparative design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Open label treatment<br>All subjects receive Trelegy and Ventolin for 2 weeks | Drug: Trelegy Ellipta 100/62.5/25Mcg Inh 30D<br>* Administration of Trelegy in all patients<br>* Other names: DPI Delivery;Drug: Ventolin 90Mcg/Actuation Inhalation Aerosol<br>* 2 hours after the administration of Trelegy, administer Ventolin in all patients<br>* Other names: pMDI Delivery;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DPI Responder Analysis in Patients With Suboptimal PIF (<60 L/Min) | Outcome = the number of subject test days (2 test days per subject) meeting responder criteria defined as: DPI Responder - a positive (>50 ml) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a negative (<50mL) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) DPI Partial Responder a positive (>50 ml) peak FEV1 response 2 hours after Trelegy® Ellipta DPI with a positive (>50 ml) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) DPI Failure - a negative (<50mL) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a positive (>50 ml) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) Irreversible - a negative (<50mL) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a negative (<50mL) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DPI Responder Analysis in Patients With Reduced PIF (<45 L/Min) | Outcome = the number of subject test days (2 test days per subject) meeting responder criteria defined as: DPI Responder - a positive (>50 ml) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a negative (<50mL) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) DPI Partial Responder a positive (>50 ml) peak FEV1 response 2 hours after Trelegy® Ellipta DPI with a positive (>50 ml) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) DPI Failure - a negative (<50mL) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a positive (>50 ml) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) Irreversible - a negative (<50mL) peak FEV1 response 2 hours after Trelegy Ellipta® DPI with a negative (<50mL) peak FEV1 response 30 minutes after Ventolin® pMDI (2.5 hours post Trelegy) | 2 weeks | 
| PIF Measurement Techniques | PIF value (L/min) based on different PIF measurement techniques | Baseline on day of testing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DPI, PIF, FEV1