BI 113608 Administered as Tablets Twice Daily Over 4 Weeks in Patients With Chronic Obstructive Pulmonary Disease Associated With Chronic Bronchitis
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Bronchitis; Bronchitis, Chronic; Lung Diseases; Pulmonary Disease, Chronic Obstructive
Intervention: Placebo to BI 113608 high dose b.i.d.; Placebo to BI 113608 low dose b.i.d.; BI 113608 high dose b.i.d.; Placebo to BI 113608 medium dose b.i.d.; BI 113608 low dose b.i.d.; BI 113608 medium dose b.i.d.
Intervention description: Film-coated tablet; Film-coated tablet; Film-coated tablet; Film-coated tablet; Film-coated tablet; Film-coated tablet
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double
Enrollment: 84.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The main objective of the current trial is to investigate safety, tolerability and
      pharmacokinetics of BI 113608 in COPD patients with symptoms of chronic bronchitis.
    

Eligibility criteria:

        Inclusion criteria:

          1. All patients must sign an informed consent consistent with ICH-GCP guidelines and
             local legislations prior to any study-related procedures, which includes medication
             washout and restrictions.

          2. All patients must have a documented diagnosis of COPD according to GOLD 2013.

          3. Post-bronchodilator 50% = FEV1 < 80% of predicted at screening visit.

          4. Post-bronchodilator FEV1/FVC <70% at screening visit.

          5. Patients must have a history of chronic bronchitis as defined by symptoms of cough and
             sputum production on most days during at least three months for the past two
             consecutive years.

          6. CAT Questionnaire at screening: a score of at least one for both cough (1st question)
             and sputum (2nd question).

          7. Males and females between 40 and 80 years (inclusive) of age, on the day of patient´s
             signature of informed consent.

          8. Patients must be current or ex-smokers with a smoking history of more than 10 pack
             years. Patients who have never smoked cigarettes must be excluded.

          9. Patients must be able to perform technically acceptable pulmonary function tests (body
             plethysmography, forced spirometry and DLCO measurement).

         10. Females must be of non-childbearing potential. Women of non-childbearing potential are
             defined as those who have undergone bilateral ovariectomy, bilateral salpingectomy or
             hysterectomy. If so, documentation confirming the surgical procedure must be available
             on the patient's source documents. A woman is also presumed to be infertile due to
             natural causes if she has been amenorrheic for more than 24 months. In questionable
             cases, a blood analysis of FSH and estradiol, which indicates the postmenopausal
             status according to the central laboratory ranges for postmenopausal females, is
             considered confirmatory.

        Exclusion criteria:

          1. Significant pulmonary disease other than COPD or other medical conditions* (as
             determined by medical history, examination, and clinical investigations at screening)
             that may, in the opinion of the investigator, result in the any of the following:

               1. Put the patient at risk because of participation in the study,

               2. Influence the results of the study,

               3. Cause concern regarding the patient's ability to participate in the study. (*e.g.
                  cardiac, gastro-intestinal, hepatic, renal, metabolic, dermatologic,
                  neurological, haematological, oncological and psychiatric; history of relevant
                  orthostatic hypotension, fainting spells or blackouts; current chronic or
                  relevant acute infections.)

          2. Patients with any lung disease other than COPD (e.g. asthma, interstitial lung disease
             (ILD), cystic fibrosis, active tuberculosis, post-TB syndrome, clinically evident
             bronchiectasis, with a history of thoracotomy with pulmonary resection).

          3. Patients with clinically relevant abnormal haematology, blood chemistry, or urinalysis
             at screening visit (Visit 1), if the abnormality defines a relevant disease as defined
             in exclusion criterion number 1.

          4. All patients with a serum glutamate oxaloacetate transferase (SGOT) or serum glutamic
             pyruvic transaminase (SGPT) or total bilirubin higher than 1.5-fold ULN or serum
             creatinine higher than normal at Visit 1 (and at all repeated tests, if applicable)
             will be excluded regardless of the clinical condition. Laboratory evaluation can be
             repeated maximum two times.

          5. A malignancy for which the patient has undergone resection, radiation therapy or
             chemotherapy within the last five years (patients with treated basal cell carcinoma
             are allowed).

          6. Patients with current relevant psychiatric disorders based on the investigator´s
             judgement.

          7. Patients with any respiratory infection (e.g. common cold, sinusitis, etc.) or COPD
             exacerbation within the six weeks prior to the screening visit (Visit 1) or between
             screening visit and randomization.

          8. Patients with a history of two or more moderate or severe COPD exacerbations per year
             within the last two years.

          9. Patients with a history of and/or active significant alcohol or drug abuse. See
             exclusion criterion number 1.

         10. Patients who are being treated with non-permitted concomitant medication.

         11. Patients with a recent history (i.e. three years or less) of heart failure or patients
             with any cardiac arrhythmia requiring drug therapy.

         12. Patients who have previously been randomised in this trial.

         13. Current participation in another clinical trial (as defined in the ICH Harmonised
             Tripartite Guideline for Good Clinical Practice (GCP)).

         14. Donation of more than 100 mL of blood within the past four weeks prior to screening.

         15. A history of additional risk factors for torsade-de-pointes (e.g., heart failure,
             relevant hypokalemia, family history of Long QT Syndrome).

         16. Pregnant or nursing women.

         17. Gastrointestinal tract surgery that might affect absorption and elimination of drugs.

         18. Patients with known hypersensitivity / allergy to the investigational medicinal
             product (IMP) or its excipients.

         19. Male Patients who do not agree to minimize the risk of female partners becoming
             pregnant from the first dosing day until two months after study completion.