Copd
Conditions
Keywords
COPD, bronchodilator, ventilatory mode, variability, forced oscillations, spirometry, plethysmography, dyspnea
Brief 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
Interventions
DRUGTRIXEO 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.
Sponsors
AstraZeneca
University Hospital, Lille
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| change in ventilation pattern complexity and variability | between V2 baseline (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose at one month) | * Noise limit: % * Lyapounov component: bits/iteration no combination possible |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | between V2 base measurement (pre-treatment) and V3 peak (2 hours (+/-30min) | 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) |
| 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) | — |
| Change impulse oscillometry or forced oscillation: resistances at 5Hz, reactance at 5Hz | between V2 base (pre-treatment) and V3 peak (2 hours (+/-30minutes) post dose | resistance and reactance: kPa/L/s |
| 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, | before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes at one month) | range 0 to 40, 40 meaning the worst condition |
| Likert scale for dyspnea and general health | before administration of BGF 160 (at V2 base (pre-treatment)) and after administration (at V3 peak (2 hours (+/-30minutes) at one month) | 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 |
| 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) | — |
Countries
France
Contacts
Primary ContactThierry PEREZ, MD
Outcome results
None listed