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Trial registered on ANZCTR


Registration number
ACTRN12618001715268
Ethics application status
Approved
Date submitted
12/10/2018
Date registered
17/10/2018
Date last updated
17/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and tolerability of an inhaled chelator in combination with antibiotic treatment for lung infection in patients with cystic fibrosis
Scientific title
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of an Inhaled Dry Powder Formulation of CaEDTA when given with Inhaled TOBI Dry Powder for treatment of Pseudomonas aeruginosa infection in Cystic Fibrosis Patients - a Phase I dose-ranging Study
Secondary ID [1] 296322 0
None
Universal Trial Number (UTN)
U1111-1222-1814
Trial acronym
TEDDPI-001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cystic fibrosis 310032 0
Condition category
Condition code
Respiratory 308783 308783 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 312649 0
Treatment: Drugs
Comparator / control treatment
Cohort 4 (control group) takes TOBI dry powder without added CaEDTA for duration of study.
Control group
Active

Outcomes
Primary outcome [1] 307773 0
Acute tolerability will be measured by FEV1 changes pre-and post-dose. This will be calculated using Easy One portable spirometer.
Timepoint [1] 307773 0
Pre dose FEV1 at Day 1, 8, 15, 22, 29
5 minute post dose FEV1 Day 1, 8, 15, 22, 29
2 and 4 hour post dose FEV1 at Day 1 and Day 29

All time points will be used to calculate tolerability

Primary outcome [2] 307774 0
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
Timepoint [2] 307774 0
Pre dose at Day 1, 15, 29
20 minutes, 2 and 4 hour post dose Day 1, 29

All time points will be used to calculate safety
Primary outcome [3] 307775 0
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.
Timepoint [3] 307775 0
Day 1 through to Day 57
Secondary outcome [1] 352835 0
Blood concentration of ethylenediamine tetraacetate (EDTA) in blood samples (millimolar, mM)
Timepoint [1] 352835 0
Blood samples will be collected pre-dose, and at ½ hour, 2 hours, and 4 hours post-dose at designated visits to assess serum CaEDTA levels at Day 1 and Day 29. A baseline CaEDTA levels will also be taken after the washout period at Day 57.The 30 minutes post-dose sample will represent the peak serum level - as is usually the case with most inhaled drugs. The clearance characteristics and serum half-life of CaEDTA are well known (serum half- life ~20 minutes and maximally up to 60 minutes).
Secondary outcome [2] 352882 0
Sputum concentration of ethylenediamine tetraacetate (EDTA) in sputum samples (millimolar, mM)
Timepoint [2] 352882 0
- pre-dose and ½-hour post-dose at enrolment Day 1 and at Day 29 to assess trough and peak levels at the different doses,
- 2 hours, 4 hours post-dose at visits Day 1 and Day 29 to assess clearance and area-under-the-curve (AUC) levels,
- single collection at the end of safety phase Day 57 for total clearance levels or evidence of accumulation.
Secondary outcome [3] 352883 0
Urine concentration of ethylenediamine tetraacetate (EDTA) in urine samples (millimolar, mM)
Timepoint [3] 352883 0
pre-dosing at Day 1 and Day 57 visits

Eligibility
Key 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
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 12175 0
Perth Children's Hospital - Nedlands
Recruitment hospital [2] 12176 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 24344 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 300917 0
Charities/Societies/Foundations
Name [1] 300917 0
Telethon Perth Children's Hospital Research Fund
Address [1] 300917 0
Research Development Unit
Department of Health
PO Box 8172
Perth Business Centre
PERTH WA 6849
Country [1] 300917 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Telethon Kids Institute
Address
15 Hospital Avenue
Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 300490 0
None
Name [1] 300490 0
Address [1] 300490 0
Country [1] 300490 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301690 0
Human Ethics University of Western Australia [EC00272]
Ethics committee address [1] 301690 0
M459, 35 Stirling Highway
Crawley WA 6009
Ethics committee country [1] 301690 0
Australia
Date submitted for ethics approval [1] 301690 0
18/07/2018
Approval date [1] 301690 0
07/09/2018
Ethics approval number [1] 301690 0
RA/4/20/4615
Ethics committee name [2] 301691 0
Children and Adolescent Health Service Human Research Ethics Committee
Ethics committee address [2] 301691 0
Perth Children's Hospital
Locked Bag 2010
NEDLANDS WA 6909
P: 6456 0516
Ethics committee country [2] 301691 0
Australia
Date submitted for ethics approval [2] 301691 0
19/09/2017
Approval date [2] 301691 0
24/01/2018
Ethics approval number [2] 301691 0
RGS0000000626

Summary
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
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 87786 0
Dr Barry Clements
Address 87786 0
Perth Children's Hospital
15 Hospital Avenue
Nedlands WA 6009
Country 87786 0
Australia
Phone 87786 0
+61863190836
Fax 87786 0
Email 87786 0
barry.clements@health.wa.gov.au
Contact person for public queries
Name 87787 0
Dr Barry Clements
Address 87787 0
Perth Children's Hospital
15 Hospital Avenue
Nedlands WA 6009
Country 87787 0
Australia
Phone 87787 0
+61863190836
Fax 87787 0
Email 87787 0
barry.clements@health.wa.gov.au
Contact person for scientific queries
Name 87788 0
Dr Barry Clements
Address 87788 0
Perth Children's Hospital
15 Hospital Avenue
Nedlands WA 6009
Country 87788 0
Australia
Phone 87788 0
+61863190836
Fax 87788 0
Email 87788 0
barry.clements@health.wa.gov.au

No data has been provided for results reporting
Summary results
Not applicable