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

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

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

Study Overview

• Status: Recruiting
• Conditions: Copd
• Intervention / Treatment: Drug: TRIXEO AEROSPHERE

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Thierry PEREZ, MD; Phone Number: +33 0320445962; Email: thierry.perez@chu-lille.fr

Study Locations

• France
  • Lille, France
    • Recruiting
    • CHU de Lille
    • Principal Investigator: Thierry PEREZ, md
    • Contact: Thierry PEREZ, md

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

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
Experimental: Experimental group; 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; 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.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Thierry PEREZ, MD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: February 21, 2023
• First Submitted That Met QC Criteria: October 30, 2023
• First Posted (Actual): October 31, 2023

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: COPD; forced oscillations; spirometry; dyspnea; variability; bronchodilator; plethysmography; ventilatory mode
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Lung Diseases, Obstructive; Signs and Symptoms, Respiratory; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Dyspnea
• Other Study ID Numbers: 2022_0422; 2022-003784-15 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No