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

Copd Clinical Trial

— VARI-OSCIL  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06110403
• Other study ID #: 2022_0422
• Secondary ID: 2022-003784-15
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 29, 2023
• Est. completion date: September 2025

Study information

• Verified date: October 2023
• Source: University Hospital, Lille
• Contact: Thierry PEREZ, MD
• Phone: 0320445962
• Email: thierry.perez[@]chu-lille.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Copd

Intervention

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.

Locations

Country	Name	City	State
France	CHU de Lille	Lille

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Lille	AstraZeneca

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Changes in FEV1 (spirometry)		between V2 base (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose
Secondary	Change Plethysmographic Functional residual capacity (FRC)		between V2 base (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)