"This is a randomised, double-blind, placebo-controlled multi-centre study to investigate safety and tolerability and to provide pharmacokinetic and pharmacodynamics information of orally inhaled multiple doses (80 mg, 160 mg or 320 mg) of the nebulised neutrophil elastase inhibitor POL6014 in patients with Cystic Fibrosis. The controlled inhalation will occur via the eFlow® nebuliser system (manufacturer: PARI Pharma GmbH, Germany)".
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
32
DL1 80 mg cohorts 1A and 1B (80 mg QD and 40 mg BID) DL2 160 mg cohorts 2A and 2B (160 mg QD and 80 mg BID) DL3 40 mg QD cohort C DL = dose Level QD= quaque die (once daily) BID= bis in die (twice daily)
Placebo will be administered orally at a dose and frequency matched to POL6014
Charité - Uniklinik Berlin, Klinik für Pädiatrie,Pneumologie, Immunologie, Erwachsenene-Mucoviszidose
Berlin, Germany
Ruhrlandklinik Westdeutsches Lungenzentrum
Essen, Germany
IKF Pneumologie GmbH & Co. KG, Institut für klinische Forschung Pneumologie
Frankfurt, Germany
Inamed GmbH, clinical unit
Gauting, Germany
Safety measured by proportion of patients who experience potential clinically significant changes in physical examinations
Time frame: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by number of patients with changes in laboratory assessments (clinical chemistry, haematology, urinanalysis)
Time frame: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by number of patients with changes in vital signs (blood pressure, pulse, respiratory rate and body temperature)
Time frame: Baseline and pre-dose through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by number of patients with changes in ECG parameters (heart rythm, ventricular rate, PR interval, QRS duration, Qt and QTc)
Time frame: Baseline and pre-dose through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by occurrence and severity of adverse events
Time frame: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by proportion of subjects who experience local irritation of the nose or pharynx by visual inspection
Time frame: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by proportion of patients who experience bronchospasm
Time frame: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Safety measured by changes in lung function parameters (FEV1, FVC)
Time frame: Baseline and pre-dose through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
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Safety measured by changes in oxygen saturation in peripheral blood as measured by pulse oximetry
Time frame: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Tolerability assessed by the number of patients who discontinue the study treatment prematurely due to Adverse Events
Time frame: Baseline through end of treatment (up to 15 days for cohorts 1A/2A/2B, up to 28 days for cohort C)
Pharmacokinetics (PK) for POL6014 and metabolites in plasma, sputum and urine
Concentration of POL6014 and relevant metabolites measured in plasma, sputum and urine
Time frame: At defined timepoints (Day1, Day 2, Day 8, Day 14, Day 15, Day 16)