None listed
Conditions
Brief summary
Aims: The aim of this study is to demonstrate clinical proof of concept of tobramycin inhaled dry powder formulation using the Orbital device in a Phase I clinical trial. Tolerability, safety (including pharmacokinetic (PK) assessments) and efficacy will be evaluated and compared to inhaled tobramycin using the standard care capsule-based TOBI Podhaler Pulmosphere therapy. Specifically, the study aims to collect information about the efficacy, tolerability and safety, of the Orbital DPI in comparison to the TOBI Podhaler. The results of this study will be used to inform a larger trial in the future. Hypotheses: It is hypothesised that the use of the Orbital Device with multi-breath inhalation manoeuvres of the same dose will be better tolerated in terms of decreased coughing generally associated with DPIs, and overall convenience in device use when compared to the TOBI Podhaler. The single dose disposable Orbital DPI device is expected to be as effective (comparable FEV1 change and decrease in Pseudomonas density), safe (maximum blood concentration – Cmax not exceeding 2µg/mL) as well as more tolerable for patients (Cough Severity Scale and Tolerability Questionnaire) which will lead to improved adherence.
Interventions
Tobramycin Inhalation Powder using Orbital DPI inhaler in Cystic Fibrosis patients.
All patients will commence 4 weeks treatment with TOBI Podhaler PulmosphereTM (Treatment A - Comparator), followed by 4 weeks with no inhalation treatment. Study participants will then be randomised in week 8 into one of the three study arms:
- TOBI Podhaler PulmosphereTM (Treatment A): control group (Comparator)
- Tobramycin-Orbital Puck B (Treatment B)*
- Tobramycin-Orbital Puck C (Treatment C)*
*The differen
Tobramycin Inhalation Powder using Orbital DPI inhaler in Cystic Fibrosis patients. All patients will commence 4 weeks treatment with TOBI Podhaler PulmosphereTM (Treatment A - Comparator), followed by 4 weeks with no inhalation treatment. Study participants will then be randomised in week 8 into one of the three study arms: - TOBI Podhaler PulmosphereTM (Treatment A): control group (Comparator) - Tobramycin-Orbital Puck B (Treatment B)* - Tobramycin-Orbital Puck C (Treatment C)* *The difference between Treatments B & C is only in the puck (hole) size and number of breaths. Treatment B has a puck hole of 0.9 mm and Treatment C has a puck hole of 0.6 mm. The inhaled tobramycin dose is the same between the 3 groups. Treatment A: 4 capsules (28mg each) twice daily for 4 weeks using TOBI Podhaler device. Treatment B: 150 mg to be administered twice daily for 4 weeks using Orbital device (puck hole of 0.9 mm) Treatment C: 150 mg to be administered twice daily for 4 weeks (puck hole of 0.6 mm). Strategies used to monitor adherence to the intervention: For Treatment A: Participants will be instructed to keep their used capsules in the bag provided (grouped per week) and bring them back to their visits so that compliance can be determined based on the number of capsules used. For treatments B& C: Orbital devices will have serial numbers and patients will be instructed to keep their used devices (grouped per week) and bring them back to their visits so that compliance can be determined. Devices to be assessed for residual drug as an indication for adherence. A subset of participants will be asked to complete additional safety assessments. This will be the first 10 participants consenting to do the additional safety assessments.
Sponsors
Woolcock Institute of Medical Research
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion criteria, which must be met at the time of study screening, are: A stable history of chronic CF disease with a FEV1 of greater than or equal to 30% predicted. Clinical stability, as determined by the clinician’s evaluation, with no pulmonary exacerbation in the past month determined by the patient’s records (e.g. need for IV antibiotics). Proven previous tolerability to TobiPodhaler. Chronic Pseudomonas aeruginosa infection as determined by the patient’s records. Aged equal to or greater than 18 years
Exclusion criteria
Exclusion criteria are: • CF patients with severe unstable conditions. • CF patients with chronic Mycobacterium abscessus and Burkholderia cepacia complex (B. cepacia) colonisation. • CF patients who are on continuous tobramycin therapy (not on alternate month tobramycin therapy) • Pregnant or lactating females or females who intend to fall pregnant within the study period.
Outcome results
None listed