Resumen

El propósito de este estudio es comparar CHF 5993 con CHF 1535 en la mejora de la función pulmonar, la reducción de las exacerbaciones moderadas y graves de EPOC y otros resultados clínicos de eficacia y seguridad en la población objetivo de sujetos.

Descripción detallada

Este es un estudio de fase III, multinacional, multicéntrico, aleatorizado, doble ciego, controlado activo, de 2 brazos paralelos para comparar la eficacia, seguridad y tolerabilidad de CHF 5993 pMDI con CHF 1535 pMDI en lo que respecta a la función pulmonar, la incidencia de exacerbaciones moderadas y graves de EPOC y otros resultados clínicos de eficacia y seguridad. Tras el cribado, los sujetos elegibles iniciarán un período de adaptación de 2 semanas utilizando sus tratamientos habituales de mantenimiento para la EPOC, tras lo cual serán aleatorizados a uno de los 2 grupos de tratamiento del estudio. Después de la aleatorización, los sujetos serán evaluados a las 4 semanas y, a continuación, a intervalos de 6 semanas durante un período de 52 semanas. Se realizará una llamada telefónica de seguimiento de seguridad una semana después de la última visita clínica. Un subgrupo de sujetos que acepten participar en el subestudio farmacocinético se someterá a evaluaciones adicionales (en un total de 3 visitas) durante las visitas programadas del estudio. Durante el estudio, los síntomas diarios, el uso de medicación de rescate y el cumplimiento con el fármaco del estudio se registrarán mediante un diario electrónico del sujeto. A lo largo del estudio se evaluarán y registrarán los medicamentos concomitantes del sujeto, los eventos adversos y la utilización de recursos sanitarios. En visitas intermedias del estudio, los sujetos se someterán a exámenes de signos vitales que incluyen peso, mediciones espirométricas y ECG de 12 derivaciones. Los síntomas y el estado de salud relacionado con la EPOC se evaluarán mediante cuestionarios específicos de la enfermedad. Se realizarán análisis rutinarios de hematología, bioquímica sanguínea y prueba de embarazo en suero antes de la inclusión y al final del estudio.

Elegibilidad

Edad mínima: 40 YearsSexo: ALL

Criterios de inclusión

Signed and dated written informed consent must be obtained prior to initiating any study-related procedures
Outpatient
Male or female subjects aged ≥40 years
Female subjects:
WOCBP fulfilling one of the following criteria: i. WOCBP with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method from the signing of the informed consent form and until the follow-up contact or ii. WOCBP with non-fertile male partners (contraception is not required in this case).
Female subjects of non-childbearing potential defined as physiologically incapable of becoming pregnant (i.e. post-menopausal or permanently sterile as per definitions given in Appendix 5). Tubal ligation or partial surgical interventions are not acceptable. If indicated, as per investigator's request, post-menopausal status may be confirmed by follicle-stimulating hormone levels (according to local laboratory ranges)
COPD diagnosis for at least 12 months before the screening visit in accordance with the definition by the GOLD 2020 Report
Current or ex-smokers who quit smoking at least 6 months prior to screening with a smoking history of at least 10 pack-years \[pack-years = (number of cigarettes per day x number of years)/20\]
COPD Assessment Test (CAT) score ≥10
A pre- and post-bronchodilator FEV1/FVC ratio \<0.70 at screening
A post-bronchodilator FEV1 \<50% predicted normal at screening and a documented history of ≥1 moderate or severe COPD exacerbation in the previous 12 months OR a post-bronchodilator FEV1 ≥50% and \<80% of predicted normal at screening and a documented history of ≥2 moderate COPD exacerbations or ≥1 severe COPD exacerbation in the previous 12 months
Subjects receiving daily inhaled maintenance therapy for their COPD, at a stable dose for at least 3 months prior to the screening and randomization visits
Documentation (including imagery and report) of chest x-ray (CXR) or CT scan performed within 6 months prior to the screening visit, without evidence of significant abnormalities (other than those related to the presence of COPD).
A cooperative attitude and ability to demonstrate correct use of the pMDI inhalers and eDiary.

Criterios de exclusión

Female subjects who are pregnant (as evident by a positive urine hCG or serum β-hCG test) or lactating
Subjects using the following medications prior to the screening visit and during the run-in period:
Systemic/oral/parenteral corticosteroids in the prior 4 weeks
Use of antibiotics for a lower respiratory tract infection (e.g. pneumonia) or COPD exacerbation in the prior 4 weeks
Any long-term chronic maintenance use of antibiotic treatment in the prior 4 weeks
Oral xanthine derivatives (e.g. theophylline) in the prior 7 days
A moderate or severe COPD exacerbation or a respiratory tract infection (e.g., pneumonia) that has not resolved ≤14 days prior to the screening visit or during the run-in period
Current treatment with non-cardioselective β-blockers
Requirement of long term (\> 15 hours daily) oxygen therapy
Known respiratory disorders other than COPD which may impact the efficacy of the study drug according to investigator's judgement.
Lung transplant surgery or lung volume reduction surgery (subjects with lung volume reduction surgery are excluded if the procedure was performed within 1 year before the Screening visit)
Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the investigator, would prevent use of anticholinergic agents
History of hypersensitivity to M3 receptor antagonists, β2 agonists, corticosteroids or any of the excipients contained in any of the study drugs used in the trial which may raise contra-indications or impact the efficacy of the study drug according to the investigator's judgement
Subject has severe, acute or uncontrolled cardiovascular condition (such as but not limited to unstable ischemic heart disease, NYHA Class IV, left ventricular failure, acute myocardial infarction or unstable angina) in the last 6 months
An abnormal and clinically significant 12-lead ECG at either the screening or randomization visit. This is characterized as but not limited to any of the following findings:
Atrial fibrillation (AF) with rapid ventricular response \> 120 bpm
Ventricular tachycardias (sustained, non-sustained \[\>3 up to 30 sec\])
Evidence of Mobitz Type II second degree or third-degree atrioventricular block
Prolonged QTcF (\>450ms for males, or \>470ms for females). This criterion is not applicable for subjects with a pacemaker or permanent AF.
Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study drug according to investigator's judgement
Unstable or uncontrolled concurrent disease which may impact the efficacy or safety of the study drug or the subject's participation in the study according to investigator's judgment
Malignancy that has not been in complete remission for at least 1 year or any untreated localized carcinomas
History of alcohol abuse and/or substance/drug abuse within 12 months prior to the screening visit
Receipt of any other investigational drug within 1 month or 5 half-lives (whichever is greater) prior to the screening visit or have been previously randomized in this trial, or are currently participating in another clinical trial
Currently in the acute phase of a pulmonary rehabilitation program within 4 weeks before the screening visit or planning to enroll in the acute phase of such a program during the study. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded
Mentally or legally incapacitated, or subjects incarcerated as a result of an official or judicial order
Major surgery in the 3 months prior to the screening visit or have a planned surgery during the trial
Non-satisfactory compliance with the eDiary (\<65% or \>135%) during the run-in period
Subjects requiring the use of spacer device or nebulizer for administration of maintenance COPD therapies.
Veins unsuitable for repeat venipuncture
Blood donation or blood loss (≥450mL) in the 4 weeks before randomization

Intervenciones

drug

Beclomethasone Dipropionate

Available in pressurized inhalation solution BDP/FF/GB 100/6/12.5μg and BDP/FF 100/6μg

drug

Glycopyrronium Bromide

Available in pressurized inhalation solution BDP/FF/GB 100/6/12.5μg

drug