The efficacy and safety of two doses of CHF6001 DPI as add-on to maintenance COPD triple therapy

Prior treatment

• Subjects under Roflumilast treatment within 6 months before study entry.
• Subjects with a moderate or severe COPD exacerbation 4 weeks prior to study entry and during run-in period.
• Subjects requiring long term (at least 15 hours daily) oxygen therapy for chronic hypoxemia.
• Subjects with lung volume reduction surgery.

Other illness

• Subjects with active cancer or a history of cancer (other than the lung) with full recovery less than 1 year after completing cancer therapy or any untreated localized carcinoma.
• Subjects with a history of allergy or hypersensitivity to anticholinergics, β2-agonists,corticosteroids, PDE-4 inhibitors or any of the excipients contained in any of the formulations used in the trial or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the investigator's opinion would contra-indicate study participation.
• Subjects with a diagnosis of depression, generalized anxiety disorder, suicidal ideation or behavior that might, according to the investigator judgement, place the patient at undue risk.
• Subjects who have clinically significant cardiovascular condition.
• Subjects with a significant neurological disease including transient ischemic attack (TIA), stroke, seizure disorder or behavioural disturbances that in investigator's opinion, would place the patient at risk by participating to the study.
• Subjects with clinically significant respiratory disorders other than COPD.
• Subjects having lung cancer or a history of lung cancer with full recovery less than 1 year after completing cancer therapy.

Other

• Subjects with a diagnosis of current asthma.
• An abnormal and clinically significant 12-lead ECG finding in relation to the subject's medical history that results in active medical problem which may impact the safety of the patient according to investigator's judgement.
• Pregnant and lactating women.
• Subjects with known α-1 antitrypsin deficiency as the underlying cause of COPD.
• Subjects with primary diagnosis of emphysema not related to COPD.

• Males and females aged ≥ 40 years with written informed consent obtained prior to any study related procedure.
• Subjects are willing and able to be trained to use correctly the electronic devices with COPD questionnaires, to understand and to perform required outcome measurements of the protocol (e.g.spirometry maneuvers etc.) and ability to understand the risks involved.
• Females are eligible to enter the study if they are of a. non- childbearing potential, b. childbearing potential, they must have a negative pregnancy test at screening and must agree to use one or more of the acceptable contraceptive measures.
• Subjects with an established diagnosis of COPD with chronic bronchitis.
• Current smokers or ex-smokers who quit smoking at least 6 months prior to screening visit, with a smoking history of at least 10 pack years.
• A post-bronchodilator FEV1 < 50% of the patient predicted normal value and a postbronchodilator FEV1/FVC ratio < 0.7 after 400μg (4 puffs x 100μg) of salbutamol pMDI or equivalent dose of albuterol pMDI in the US.
• A documented history (e.g. medical record verification) of at least one moderate or severe COPD exacerbation in the previous year.
• Symptomatic subject at screening defined as having a CAT score ≥10.
• Subjects prescribed with maintenance triple therapy (free or fixed combination of ICS, LABA, LAMA) according to GOLD 2020 recommendations, for at least 12 months prior to screening and receiving regular maintenance triple therapy for at least 3 months prior to the screening visit. ICS must be in an approved dose for COPD.
• Subjects are willing and able to be trained to use correctly the DPI inhalers (NEXThaler®).