None listed
Conditions
Brief summary
This will be an open-label, unblinded, dose-escalating study. Participants will consist of 24 CF patients (three treatment groups and one control group) who are about to start a standard 4-week course of inhaled TOBI dry powder for outpatient (home) treatment of Pseudomonas aeruginosa infection. Hypothesis: Inhalation of a dry powder chelator in combination with antibiotic therapy is safe and well tolerated in patients with cystic fibrosis
Interventions
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 capsule
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.
Sponsors
Telethon Kids Institute
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
12 Years to No maximum
Healthy volunteers
No
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 - 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. - Patient capable of using a dry powder inhaler
Exclusion criteria
- Patients who in addition to culturing PsA in their sputum, have also cultured B Cepacia, Staph aureus, Achromobacter, Stenotrophomonas, Acinetobacter, and non-tuberculous mycobacterium species within the last year. - Known hypersensitivity to the investigational product or its components or known relevant medication allergy - Currently taking oral prednisone or IV methylprednisolone for ABPA - Participation in another study with an investigational drug within 1 month of the planned first dose of investigational product - Known relevant substance abuse - Female patients who are pregnant or lactating - Clinically significant disease or other medical condition other than CF or CF-related conditions that would, in the opinion of the Investigator, compromise the safety of the patient or quality of the data
Outcome results
None listed