Peak Inspiratory Flow and Dry Powder Inhaler Performance in COPD

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

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

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: Trelegy Ellipta 100/62.5/25Mcg Inh 30D; Drug: Ventolin 90Mcg/Actuation Inhalation Aerosol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Farmington Hills, Michigan, United States, 48336
      • Pulmonary Research Institute of Southeast Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pulmonary Research Institute of Southeast Michigan
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Gary T Ferguson, MD, Pulmonary Research Institute of Southeast Michigan

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2020
• Primary Completion (Actual): December 15, 2021
• Study Completion (Actual): December 15, 2021

Study Registration Dates

• First Submitted: October 19, 2020
• First Submitted That Met QC Criteria: October 22, 2020
• First Posted (Actual): October 28, 2020

Study Record Updates

• Last Update Posted (Actual): May 8, 2023
• Last Update Submitted That Met QC Criteria: May 4, 2023
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: FEV1; DPI; PIF
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Respiratory Aspiration; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol
• Other Study ID Numbers: 001 (NavyGHB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes