Pharmacokinetic Evaluation and Tolerability of Dry Powder Tobramycin by a Novel Device in Patients With Non Cystic Fibrosis Bronchiectasis
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pharmacokinetic Evaluation and Tolerability of Dry Powder Tobramycin by a Novel Device in Patients With Non Cystic Fibrosis Bronchiectasis|
- Actual dose (dose minus remainder in inhaler after inhalation) of tobramycin [ Time Frame: one day ] [ Designated as safety issue: Yes ]
- Area Under the plasma concentration versus time curve from 0 -12 hours (AUC0-12) of tobramycin •Area Under the plasma concentration versus time curve from 0 -12 hours (AUC0-12) of tobramycin [ Time Frame: One day ] [ Designated as safety issue: Yes ]
- Maximum plasma concentration (Cmax ) of tobramycin [ Time Frame: One day ] [ Designated as safety issue: Yes ]
- Time to maximum plasma concentration (Tmax) of tobramycin [ Time Frame: One day ] [ Designated as safety issue: Yes ]
- Absorption rate constant (Ka) of tobramycin [ Time Frame: One day ] [ Designated as safety issue: Yes ]
- Terminal elimination half-life (T1/2 el ) of tobramycin [ Time Frame: One day ] [ Designated as safety issue: Yes ]
- Clearance following pulmonary administration (CL/F) (F= bioavailability) of tobramycin [ Time Frame: One day ] [ Designated as safety issue: Yes ]
- Decrease of FEV1 in percentage measured by spirometry [ Time Frame: One day ] [ Designated as safety issue: Yes ]
- Number of Participants with Adverse Events [ Time Frame: One day ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2013|
|Study Completion Date:||December 2014|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Patients with bronchiectasis
Tobramycin dry powder 30 mg inhalation per dose; Dose escalation: 30-60-120 and 240 mg, each one time. One dose per week.
Other Name: Dry powder tobramycin free base
Rationale: Bronchiectasis is a persistent and frequently progressive condition characterized by dilated and thick-walled bronchi retaining sputum. The main symptoms of bronchiectasis are cough and chronic sputum production. There is a state of constant colonization with bacteria, which frequently causes exacerbations. The presence of Pseudomonas aeruginosa is an unfavorable prognostic indicator and is associated with increased sputum production, more extensive bronchiectasis on HR-CT of the thorax, more hospitalizations and reduced quality of life. Until now, most patients with non-CF bronchiectasis who are colonized with P. aeruginosa receive inhaled tobramycin every other month, by use of a nebulizer. However, this delivery system has several disadvantages, like a low lung deposition and pollution with tobramycin in the surrounding environment. With an efficient dry powder inhaler (DPI), a three to six fold higher lung deposition compared to a nebulizer can be obtained. Therapy with a DPI is also less time consuming compared to nebulisation. Nebulised tobramycin is used most in routine care; there is also one, rather poorly characterized DPI for tobramycin available, though this DPI is not registrered for non-CF bronchiectasis. We will investigate dry powder tobramycin (DP tobramycin) in a novel device in patients with non-CF bronchiectasis colonized with P. aeruginosa.
Objective: The main objectives are to investigate the pharmacokinetic properties of DP tobramycin at different dosages together with the local tolerability of DP tobramycin via the Cyclops® at different dosages.
Study design: single center, single ascending, single dose, response study. Study population: 8 patients with non-CF bronchiectasis
Main study parameters:
The following pharmacokinetic parameters will be calculated: actual dose (dose minus remainder in inhaler after inhalation), AUC0-12 (area under the curve from 0 -12 h), Cmax (maximum plasma concentration), Tmax (time to maximum plasma concentration), Ka (absorption rate constant), T1/2 el (terminal elimination half-life), CL/F (clearance following pulmonary administration (F= bioavailability)).
Local tolerability of DP tobramycin is determined by scoring adverse events, specifically coughing, and lung function measurement.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: All participants included in this study are patients recruited from the outpatient department of pulmonology. To investigate safety, lung function tests will be performed and the occurrence of adverse events will be scored.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02035488
|University Medical Center Groningen|
|Principal Investigator:||Huib Kerstjens, MD, PhD||University Medical Center Groningen|