Impact of Long-acting Bronchodilator- -Corticoid Inhaled Therapy on Ventilation, Lung Function and Breathlessness

Study Overview
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Brief Summary
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Multicentre, prospective, non-randomised, single-arm, open label, mechanistic study to investigate the mechanism of action of BGF 160 on ventilation pattern complexity and variability

Official Title
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Impact of Inhaled BGF 160 on Complexity and Variability of Tidal Breathing and Oscillatory Mechanics in Stable COPD Patient

Conditions
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Copd

Intervention / Treatment
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* Drug: TRIXEO AEROSPHERE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed informed consent prior to any study specific procedure Female or male subjects aged 40-75 years inclusive at the time of enrolment (Visit 1) Documented history of COPD with a post-bronchodilator FEV1/FVC <0.70 and a post-bronchodilator 30 % < FEV1 <70% of predicted normal value (according to ERS 1993 reference values for spirometry ) at screening Smoking history > 10 pack-years Baseline significant dyspnea with a mMRC ≥ 2 Exclusion Criteria: History or current diagnosis of asthma or ACOS (asthma-COPD overlap syndrome) Respiratory infection or COPD exacerbation within 6 weeks (2 months if it resulted in hospitalization) prior to screening Clinically significant or relevant cardiovascular conditions, laboratory tests, electrocardiogram (ECG) parameters: Unstable angina/acute coronary syndrome, or Coronary Artery Bypass Grafting (CABG), Percutaneous Coronary Intervention (PCI) or myocardial infarction within the past 6 months. Congestive heart failure New York Heart Association (NYHA) class III/IV. Structural heart disease (hypertrophic cardiomyopathy, significant valvular disease). Paroxysmal (within the past 6 months) or symptomatic chronic cardiac tachyarrhythmia. Left bundle branch or high-degree AV block (second degree AV block type 2 and third degree AV block) unless the patient has a pacemaker. Sinus node dysfunction with pauses. Ventricular pre-excitation and/or Wolff-Parkinson-White syndrome. QTcF interval >470 msec (QT interval corrected using Fridericia's formula; QTcF=QT/[RR1/3]). Any other ECG abnormality deemed clinically significant by the Investigator. Bradycardia with ventricular rate < 45 bpm. Uncontrolled hypertension (> 165/95 mmHg). Clinically relevant respiratory conditions (other than COPD) Severe renal impairment eGFR < 30 Hepatic impairment Narrow-angle glaucoma that, in the opinion of the Investigator, has not been adequately treated. Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that is clinically significant Patients not able to perform IOS, spirometry, plethysmography, or VT acquisition (10 min) Any contraindication to LABA or LAMA drugs or to Inhaled corticosteroids Pregnancy or breastfeeding Woman of childbearing age without effective contraception Any type of cancer within 5 years Patients under guardianship Refuse or incapacity to give an informed consent Absence of social insurance

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>Symptomatic COPD patients in stable condition treated with BGF 160 (Trixéo Aerosphere®), a combination of budesonide, formoterol and glycopyrronium in a metered dose inhaler, taken twice a day | Drug: TRIXEO AEROSPHERE<br>* BGF 160 (Breztri Aerosphere™ in USA, Trixeo™ in France) Inhalation aerosol: pressurized metered dose inhaler containing a combination of budesonide (160 mcg), glycopyrrolate (9 mcg) and formoterol fumarate (4.8 mcg) as an inhalation aerosol. Oral inhalation: 2 inhalations of BGF 160 twice daily for 30 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in ventilation pattern complexity and variability | Noise limit: % Lyapounov component: bits/iteration no combination possible | between V2 baseline (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose at one month) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change impulse oscillometry or forced oscillation: resistances at 5Hz, reactance at 5Hz | resistance and reactance: kPa/L/s | between V2 base (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose | 
| Changes in FEV1 (spirometry) |  | between V2 base (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose | 
| Change Plethysmographic Functional residual capacity (FRC) |  | between V2 base (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose | 
| Changes measurement for noise limit, respiratory frequency, volume, largest Lyapounov component, resistances at 5Hz, reactance at 5Hz, FEV1and FRC versus TDI at V3 | TDI at V3 (in term of continuous variable and in term of binary variable responder/non responder; a response is defined by a change in TDI ≥ +1 between baseline and V3) | between V2 base measurement (pre-treatment) and V3 peak (2 hours (+/-30min) | 
| Baseline dyspnea index ( BDI) |  | before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes) at one month) | 
| Transition dyspnea index (TDI) |  | before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes) at one month) | 
| Modified dyspnea profile ( MDP) |  | before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes) at one month) | 
| CAT score : COPD assessment test, | range 0 to 40, 40 meaning the worst condition | before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes at one month) | 
| Likert scale for dyspnea and general health | Likert scale change in dyspnea : - 3 to + 3, + 3 maximal improvement, -3 maximal deterioration Likert scale change in general health : - 3 to + 3, + 3 maximal improvement, -3 maximal deterioration | before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes) at one month) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dyspnea, COPD, bronchodilator, ventilatory mode, variability, forced oscillations, spirometry, plethysmography