Untersuchung der Wirkweise von QBW251 bei Patienten mit chronisch obstruktiver Lungenerkrankung (COPD) im Rahmen einer randomisierten, placebo-kontrollierten, doppelblinden Studie mit zwei parallelen Behandlungsgruppen

Product Code: QBW251
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not yet defined
Current Sponsor code: QBW251
Other descriptive name: CFTR potentiator
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Inclusion criteria:
•Patients who have signed an Informed Consent Form prior to initiation of any study-related procedure.
•Male and female adults aged =40 years at screening.
•Patients with stable COPD, stages GOLD 2-4, according to the current GOLD strategy (GOLD 2019) at screening.
•Patients with a post-bronchodilator FEV1/FVC < 0.70 at screening
•Patients with airflow limitation indicated by a post-bronchodilator FEV1 = 30% and FEV1 < 80% of the predicted normal at Screening who must have had at least 2 documented moderate or at least 1 documented severe exacerbation(s) in the 12 months prior to study entry.
•Patients with sputum bacterial load (log10=105 CFU/mL) with at least one strain of potentially pathogenic
microorganism at screening (H influenzae, H parainfluenzae, P aeruginosa, S pneumoniae, S aureus, Moraxella catarrhalis, Enterobacteriaceae).
•Patients who have been treated with a combination of LABA/LAMA or LABA/ICS or LABA/LAMA/ICS at a stable dose for the last 3 months prior to screening.
COPD patients are allowed to stay on macrolides as background therapy if they have bronchiectasis as a secondary diagnosis and if they are treated with them at a stable dose 3 months before screening.
•Patients with plasma fibrinogen level =350 mg/dL at screening.
•A COPD Assessment Test (CAT) score of at least 10 at screening.
•Current or ex-smokers who have a smoking history of at least 10 pack years at screening. (e.g. 10 pack years = 1 pack/day x 10 years, or 0.5 pack/day x 20 years) at screening.
•Patients featuring chronic bronchitis, defined as productive cough that occurs on most days (defined as >50% of days) during at least 3 consecutive months in the year prior to screening, as assessed by documentation of patient recollection(anamnesis) or documented in patients' records.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
•Patients with a history of long-QT syndrome or whose QTcF interval at screening (Fridericia method) is prolonged (QTcF >450 ms in males, >460 ms in females).
•Patients who have a clinically significant ECG abnormality before randomization.
•Clinical laboratory values abnormalities (including Gamma GT, AST, ALT, total bilirubin or creatinine) considered as clinically significant in the opinion of the Investigator at screening.
•Patients who have clinically significant renal, cardiovascular (such as but not limited to unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, myocardial infarction), neurological, endocrine, immunological, psychiatric, gastrointestinal, or hematological abnormalities, which could interfere with the assessment of the efficacy and safety of the study treatment, or patients with uncontrolled Type II diabetes.
•Patients with a history or current treatment for hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or an AST/ALT of more than 1.5x ULN or abnormal PT/INR at screening.
•Patients with a history of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. Patients with a history of cancer and 5 years or more disease free survival time may be included in the study by agreement with Novartis Medical Monitor on a case-by-case basis.
•Patients who develop a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization during screening. Re-screening is permitted after a minimum of 2 weeks after the resolution of the COPD exacerbation (i.e. 2 weeks after the stop of SOC therapy for exacerbation).
•Patients who have had a respiratory tract infection within 4 weeks prior to screening. If a respiratory tract infection occurs during screening, patients can be re-screened after a minimum of 2 weeks after resolution of the respiratory tract infection.
•Patients with history of asthma or any other clinically relevant lung diseases.
•Patients with suspected active pulmonary tuberculosis or currently being treatment for active pulmonary tuberculosis.
Note: Patients with a history of pulmonary tuberculosis can be enrolled if they meet the following requirements: history of appropriate drug treatment followed by negative imaging results within 12 months prior to screening suggesting low probability of recurrent active tuberculosis.
•Patients with pulmonary lobectomy, lung volume reduction surgery, bronchoscopic lung volume reductions, or lung transplantation.
•Patients participating in or planning to participate in the active phase of a supervised pulmonary rehabilitation program during the trial. Participation in a maintenance program is permitted. Note: the supervised pulmonary rehabilitation program as a maintenance program has to be ongoing for at least 3 months at the time of enrollment.
•Patients with a body mass index (BMI) of more than 40 kg/m2.
•Pregnant or nursing (lactating) women where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
•Women of childbearing potential defined as all women physiologically capable of becoming pregnant,unless they are using acceptable effective methods of contracepti