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Pharmacokinetic Evaluation and Tolerability of Dry Powder Tobramycin by a Novel Device in Patients With Non Cystic Fibrosis Bronchiectasis

Information source: University Medical Center Groningen
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Bronchiectasis

Intervention: Tobramycin (Drug)

Phase: Phase 1/Phase 2

Status: Completed

Sponsored by: University Medical Center Groningen

Official(s) and/or principal investigator(s):
Huib Kerstjens, MD, PhD, Principal Investigator, Affiliation: University Medical Center Groningen

Summary

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. Until now, most patients with non-CF bronchiectasis 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. We will investigate dry powder tobramycin (DP tobramycin) in a novel device in patients with non-CF bronchiectasis. The main objectives of this study 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.

Clinical Details

Official title: 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

Primary outcome:

Actual dose (dose minus remainder in inhaler after inhalation) of tobramycin

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

Maximum plasma concentration (Cmax ) of tobramycin

Time to maximum plasma concentration (Tmax) of tobramycin

Absorption rate constant (Ka) of tobramycin

Terminal elimination half-life (T1/2 el ) of tobramycin

Clearance following pulmonary administration (CL/F) (F= bioavailability) of tobramycin

Decrease of FEV1 in percentage measured by spirometry

Number of Participants with Adverse Events

Detailed description: 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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion criteria:

- Age 18 years or older

- Obtained informed consent

- Patients having bronchiectasis (confirmed with HR-CT of the chest)

Exclusion criteria:

- Pregnant or breast feeding

- Subjects with known or suspected renal, auditory, vestibular or neuromuscular

dysfunction, or with severe, active haemoptysis,

- History of adverse events on previous tobramycin or other aminoglycoside use

- No concurrent use of cyclosporin, cisplatin, amfotericin B, cephalosporins,

polymyxins, vancomycin and NSAIDs.

Locations and Contacts

University Medical Center Groningen, Groningen, Netherlands
Additional Information

Starting date: October 2013
Last updated: December 15, 2014

Page last updated: August 23, 2015

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