A phase IIa, randomized, double blind, placebo-controlled study to assess the effect of PBF-680 in patients with moderate to severe COPD on top of standard medication.

INTERVENTION: Product Code: PBF‐680 Pharmaceutical Form: Capsule, hard INN or Proposed INN: (1R,3S)‐3‐[(5‐cyano‐4‐phenyl‐1,3‐thiazol‐2‐yl)carbamoyl] cyclopentane carboxylic acid Current Sponsor code: PBF‐680 Other descriptive name: PBF‐680 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Patients with moderate to severe Chronic Obstructive Pulmonar Disease (COPD) ; MedDRA version: 21.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855 Therapeutic area: Diseases [C] ‐ Respiratory Tract Diseases [C08] PRIMARY OUTCOME: Main Objective: To investigate the effect of PBF‐680 on change from baseline in plasma eosinophil count on Day 28 when administered to patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD) on top of standard medication. Primary end point(s): Primary Endpoint:; ; ‐Change from baseline in the blood eosinophil count. Secondary Objective: Assesing:; ‐ Change from baseline in Through FEV1 24h on D14 and D28.; ‐ Change from baseline in pre‐bronchodilator FEV1 3h on D1, D14 and D28; ‐ Change from baseline in post‐bronchodilator FEV1 3h on D1, D4 and D28.; ‐ Investigate the effects of PBF‐680 on COPD symptoms, as measured by the Baseline Dyspnea Index (BDI)/ Transition Dyspnea Index (TDI), StGeorge's Respiratory Questionnaire (SGRQ‐C), the modified Medical Research Council (mMRC) scale and the COPD Assessment Test (CAT). ; ‐ To investigate the safety of PBF‐680 when administered for 4 weeks in patients with COPD on top of standard medication (long‐acting bronchodilators and Inhaled corticosteroids (ICS), as measured by AEs, electrocardiograms (ECGs) and vital signs.; ‐ To determine PBF‐680 plasma exposure till 3h post administration on days; on D1, D14 and D28.; ‐ To compare levels of selected blood inflammatory biomarkers (regarding; basal and placebo like TNF alpha, Interleukins and C‐reactive protein (CRP). Timepoint(s) of evaluation of this end point: Before, during and at the end of study treatment. SECONDARY OUTCOME: Secondary end point(s): Secondary Endpoints:; ; ‐ Change from baseline in Through FEV1 (23h30) after 4 weeks of treatment. ; ‐ Change from baseline in Through FEV1 (23h30) after 2 weeks of treatment. ; ‐ Change from baseline in prebronchodilator FEV1 at 3h post administration on Day 1, Day 14 and Day 28; ‐ Change from baseline in postbronchodilator FEV at 3h post administration on Day 1, Day 14 and Day 28; ‐ Change from baseline in the SGRQ‐C, BDI/TDI, COPD Assessment Test (CAT) and mMRC breathlessness scales.; • Safety and tolerability:; ‐ Continuous monitoring of adverse events; ‐ Laboratory safety tests (hematology, biochemistry and urinalysis); ‐ 12‐lead ECG (including QTcF and heart rate), supine vital signs over visit 2‐4.; ‐ PBF‐680 plasma concentration till 3h post administration on Day 1, Day 14 and Day 28.; ‐ Change from baseline on biomarkers of inflammation: TNF alpha, Interleukins and C‐reactive protein (CRP) Timepoint(s) of evaluation of this end point: Before, during and at the end of study treatment. INCLUSION CRITERIA: 1. Sign an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study. 2. Male or female aged between 40 and 80 years inclusive, at the time of informed consent. 3. If male: unless surgically sterile, must agree to meet the following from the first dose up to the Follow‐up, 2 weeks after the last dose of study medication: • Not donate sperm • Either: be sexually abstinent in accordance with a patient's usual and preferred lifestyle (but agree to abide by the contraception requirements below should their circumstances change) Or: use a condom with all sexual partners. If the partner is a female of childbearing potential the condom must be used with spermicide and a second reliable form of contraception must also be used (e.g. diaphragm/cap with spermicide, established hormonal contraception, intra‐uterine device) If female: be of non‐childbearing poten