BUDESONIDE, GLYCOPYRRONIUM BROMIDE, FORMOTEROL FUMARATE DIHYDRATE for Chronic obstructive pulmonary disease

Inclusion criteria

• {"criterion_text":"-Provision of signed informed consent prior to any study specific procedure"}
• {"criterion_text":"-Female or male subjects aged 40-75 years inclusive at the time of enrolment (Visit 1)"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Smoking history > 10 pack-years"}
• {"criterion_text":"-Baseline significant dyspnea with a mMRC ≥ 2"}

Exclusion criteria

• {"criterion_text":"-History or current diagnosis of asthma or ACOS (asthma-COPD overlap syndrome)"}
• {"criterion_text":"-Any contraindication or allergy to LABA or LAMA drugs or to Inhaled corticosteroids"}
• {"criterion_text":"-Treatment by an azole systemic antifungal (itraconazole, fluconazole…)"}
• {"criterion_text":"-Treatment by a protease inhibitor or cobicistat for HIV"}
• {"criterion_text":"-Pregnancy or breastfeeding"}
• {"criterion_text":"-Woman of childbearing age without effective contraception"}
• {"criterion_text":"-Any type of cancer within 5 years"}
• {"criterion_text":"-Patients under guardianship"}
• {"criterion_text":"-Refuse or incapacity to give an informed consent"}
• {"criterion_text":"-Absence of social insurance"}
• {"criterion_text":"-Respiratory infection or COPD exacerbation within 6 weeks (2 months if it resulted in hospitalization) prior to screening"}
• {"criterion_text":"-Clinically significant or relevant cardiovascular conditions, laboratory tests, electrocardiogram (ECG) parameters: o\tUnstable angina/acute coronary syndrome, or Coronary Artery Bypass Grafting (CABG), Percutaneous Coronary Intervention (PCI) or myocardial infarction within the past 6 months. o\tCongestive heart failure New York Heart Association (NYHA) class III/IV. o\tStructural heart disease (hypertrophic cardiomyopathy, significant valvular disease). o\tParoxysmal (within the past 6 months) or symptomatic chronic cardiac tachyarrhythmia. o\tLeft bundle branch or high-degree AV block (second degree AV block type 2 and third degree AV block) unless the patient has a pacemaker. o\tSinus node dysfunction with pauses. o\tVentricular pre-excitation and/or Wolff-Parkinson-White syndrome. o\tQTcF interval >470 msec (QT interval corrected using Fridericia's formula; QTcF=QT/[RR1/3]). o\tAny other ECG abnormality deemed clinically significant by the Investigator. o\tBradycardia with ventricular rate < 45 bpm. o\tUncontrolled hypertension (> 165/95 mmHg)."}
• {"criterion_text":"-Clinically relevant respiratory conditions (other than COPD)"}
• {"criterion_text":"-Severe renal impairment eGFR < 30"}
• {"criterion_text":"-Hepatic impairment"}
• {"criterion_text":"-Narrow-angle glaucoma that, in the opinion of the Investigator, has not been adequately treated."}
• {"criterion_text":"-Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that is clinically significant"}
• {"criterion_text":"-Patients not able to perform IOS, spirometry, plethysmography, or VT acquisition (10 min)"}

Primary endpoints

• {"endpoint_text":"-Multiple primary endpoints characterizing the change in ventilation pattern complexity and variability between V2 baseline (pre-treatment) and V3 peak (2 hours (+/-30min) post dose at one month) : noise limit, respiratory frequency, volume and largest Lyapounov component (an indicator of the sensitivity of the system to initial condition.","definition_or_measurement_approach":"Change between V2 baseline (pre-treatment) and V3 peak (2 hours (+/-30min) post dose at one month) measured for noise limit, respiratory frequency, tidal volume and largest Lyapounov exponent as indicators of ventilation pattern complexity and variability."}

Secondary endpoints

• {"endpoint_text":"-Change between V2 base (pre-treatment) and V3 peak (2 hours (+/-30min) post dose) of : -\tImpulse oscillometry or forced oscillation: resistances at 5Hz, reactance at 5Hz -\tSpirometry: Changes in FEV1 -\tPlethysmographic Functional residual capacity (FRC)","definition_or_measurement_approach":"Differences between V2 baseline and V3 peak (2h +/-30min) for IOS (resistance at 5Hz, reactance at 5Hz), spirometry (FEV1 change) and plethysmographic FRC."}
• {"endpoint_text":"-Changes between V2 base measurement (pre-treatment) and V3 peak (2 hours (+/-30min) measurement for noise limit, respiratory frequency, volume, largest Lyapounov component, resistances at 5Hz, reactance at 5Hz, FEV1and FRC versus 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)","definition_or_measurement_approach":"Associations of change in physiological measures (noise limit, respiratory frequency, volume, Lyapounov component, resistances/reactance at 5Hz, FEV1, FRC) between V2 and V3 with Transition Dyspnea Index (TDI) at V3; TDI analyzed as continuous and dichotomized (responder if ≥ +1)."}
• {"endpoint_text":"-Dyspnea and symptom scores: -\tBaseline dyspnea index ( BDI) -\tTransition dyspnea index (TDI) -\tModified dyspnea profile ( MDP) -\tCAT score -\tLikert scale for dyspnea and general health","definition_or_measurement_approach":"Patient-reported dyspnea and symptom scales (BDI, TDI, MDP, CAT, Likert scales) measured at specified visits to assess symptoms and changes."}
• {"endpoint_text":"-Noise limit, respiratory frequency, volume, largest Lyapounov component, resistances at 5Hz, reactance at 5Hz, FEV1, FRC, and VAS dyspnea/chest tightness","definition_or_measurement_approach":"Collection of physiological parameters (noise limit, respiratory frequency, tidal volume, Lyapounov component, IOS resistances/reactance at 5Hz, FEV1, FRC) and VAS for dyspnea/chest tightness at defined timepoints (V2, V3) to characterize effects."}

France

Earliest CTIS Part Ii Submission Date

18-11-2024

Latest Decision Or Authorization Date

16-12-2024

Processing Time Days

28

Number Of Sites

4

Number Of Participants

35

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Lille

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France