Safety and tolerability of an inhaled chelator in combination with antibiotic treatment for lung infection in patients with cystic fibrosis

INTERVENTION: Cohort One Tobramycin (TOBI dry powder) ‐ dry powder capsules 112mg twice daily for 4 weeks Calcium disodium ethylenediamine tetraacetate (dry powder capsules ‐ which are inserted into a mododose inhaler which pierces the capsule so it can be inhaled) Week 1 ‐ 37.5mg twice daily Week 2 ‐ 75mg twice daily Week 3 ‐ 75mg twice daily Week 4 ‐ 150mg twice daily Cohort Two Tobramycin (TOBI dry powder) 112mg twice daily for 4 weeks Calcium disodium ethylenediamine tetraacetate (dry powder capsules) Week 1 ‐ 37.5mg twice daily Week 2 ‐ 75mg twice daily Week 3 ‐ 75mg twice daily Week 4 ‐ 75mg four times a day Cohort Three Tobramycin (TOBI dry powder) 112mg twice daily for 4 weeks Calcium disodium ethylenediamine tetraacetate (dry powder capsules) Week 1 ‐ 37.5mg twice daily Week 2 ‐ 75mg twice daily Week 3 ‐ 75mg twice daily Week 4 ‐ 150mg twice daily Cohort Four Tobramycin (TOBI dry powder) 112mg twice daily for 4 weeks Cohort One, Two and Three will use participant diary for drug adherence. All used and unused CaEDTA dry powder capsules will be returned to site by participant at every visit and will be counted for drug adherence. Site staff will be going through tobramycin adherence with the participant at every visit and noting down any missed doses. CONDITION: cystic fibrosis PRIMARY OUTCOME: Acute tolerability will be measured by FEV1 changes pre‐and post‐dose. This will be calculated using Easy One portable spirometer. Safety ‐ Adverse events, respiratory symptoms ; ; Any changes in health ‐ if participant had headache, increased cough, stomach cramps etc. will be collected from participant throughout the study. They will have a hand out to take home to fill in time and dates of heath events, plus coordinator will go through any changes in health at every visit. ; ; Coordinator will ask participant at every visit whether they have had a change in respiratory symptoms i.e. ‐ increased cough, increased sputum production, shortness of breath, wheezing etc. Safety ‐ blood tests include kidney and liver function (creatinine, ALT, GGT), iron‐ related markers (ferritin, iron, transferrin and transferrin saturation), as well as haemoglobin, blood urea nitrogen, calcium and magnesium SECONDARY OUTCOME: Blood concentration of ethylenediamine tetraacetate (EDTA) in blood samples (millimolar, mM) Sputum concentration of ethylenediamine tetraacetate (EDTA) in sputum samples (millimolar, mM) Urine concentration of ethylenediamine tetraacetate (EDTA) in urine samples (millimolar, mM) INCLUSION CRITERIA: ‐ Male or female patients 12 or more years of age with a documented diagnosis of CF (positive sweat chloride test, genotype with two identifiable CF mutations) accompanied by one or more clinical features consistent with the CF phenotype ‐ FEV1 >40% of predicted values ‐ At least one positive sputum culture for PsA in the previous 12 months ‐ Due to start a four week course of inhaled tobramycin dry powder for treatment of PsA infection ‐ Must be able to give informed consent or have legally acceptable representative who can give informed consent in accordance with ICH/GCP ‐ Pati ‐ Females of child‐bearing potential must agree to use an acceptable method of contraception for the duration of the trial and to have 4 pregnancy tests. Appropriate forms of contraception include; willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and 3‐week follow‐up period.