The main objectives are to investigate the pharmacokinetic properties of DP tobramycin via the Cyclops® at different dosages in children with CF, together with the local tolerability.
ID
Source
Brief title
Condition
- Bacterial infectious disorders
- Congenital respiratory tract disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The following pharmacokinetic parameters will be calculated: AUC0 till 8-12
(area under the curve from 0 till 8-12 h)
Secondary outcome
The following pharmacokinetic parameters will be calculated: actual dose (dose
minus remainder in inhaler after inhalation), 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.
Background summary
Cystic fibrosis is the most common life-shortening autosomal recessive disease
among Caucasian populations. It is a chronic progressive disease causing
deterioration of pulmonary function, and of general condition as well. Although
it is a multisystem disease, the primary cause of death is respiratory failure,
resulting from chronic pulmonary infection. Pseudomonas aeruginosa is the
predominant pathogen. The presence of P. aeruginosa in patients with CF is an
unfavourable prognostic indicator and is associated with accelerated lung
tissue destruction and loss of lung function, subsequently leading tot
increased morbidity and mortality. Preventing, limiting and treating chronic
infection with P. aeruginosa is therefore crucial in the management of CF, to
improve survival and quality of life.
Currently most children with CF who are colonized with P. aeruginosa receive
inhaled tobramycin every other month, mostly by use of a nebulizer. This
delivery system however has several disadvantages. For example, the
nebulisation itself and the cleaning of the nebulizer is time consuming. This
places a high burden on a CF patient, especially for children, which will
negatively influence compliance and quality of inhalation, thereby jeopardizing
effective treatment. Therapy with a (disposable) dry powder inhaler (DPI) is
less time consuming. Besides this, nebulisation brings the risk of
auto-re-infection of the patient (contamination of nebulisation fluid and/or
device). Other more technical disadvantages of nebulisation are a low lung
deposition and pollution with tobramycin in the surrounding environment. With
an efficient DPI, a three to six fold higher lung deposition compared to a
nebulizer can be obtained. Nebulised tobramycin is used most in routine care,
but sometimes a DPI is used, for example the Podhaler®. Although the dispersion
behaviour of these dry powder systems is often good, the engineering processes
make the products expensive, and the high excipient fractions make the inhaled
powder doses high. Furthermore because these devices are not disposable, there
is a risk of bacterial resistance development in the device. Next to this is
the hygroscopic nature of tobramycin a risk for good dispersion when a used DPI
is stored inappropriately and powder residues in the inhaler become sticky or
even liquefied when they absorb moisture from the air. There is one disposable
DPI for tobramycin available, called the Cyclops®, though this DPI is not
registered for children with CF. We will investigate dry powder tobramycin (DP
tobramycin) in the Cyclops® in children with CF.
Study objective
The main objectives are to investigate the pharmacokinetic properties of DP
tobramycin via the Cyclops® at different dosages in children with CF, together
with the local tolerability.
Study design
Single center, single ascending, single dose study.
Intervention
All patients have to inhale dry powder tobramycin via the Cyclops in three
different dosages, and once tobramycin via wet nebulization.
Study burden and risks
Target population of this study consists of children aged 6-18 years, because
no information is available for inhalation of tobramycin using the Cyclops® in
this population. Moreover, especially for children with CF a more easy to use
and less time consuming treatment may improve quality of life.
Children participating in this study will receive instructions before using the
DPI and their inspiratory flow will be tested. Before each test dose an
infusion catheter will be inserted and after each test dose blood will be
collected. To investigate safety, lung function tests will be performed before
and 15, 30 and 90 minutes after inhalation and the occurrence of adverse events
will be scored.
Tobramycin is a registered drug for the treatment of chronic P. aeruginosa
infection in CF-patients of 6 years and older. Inhalation of tobramycin is
proven to be effective and safe in multiple studies. Dry powder tobramycin
inhalation via the Cyclops® has been evaluated in adults with non-CF
bronchiectasis. In this study a good drug dose * serum concentration
correlation was obtained in adults, and the dry powder tobramycin inhalation
via the Cyclops has been found save with only mild tobramycin-related cough was
reported once.
Hanzeplein 1 Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1 Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
- Clinical diagnosis of CF and a positive sweat test or two CF-related mutations
- Age 6 - 18 years
- Ability to breathe through a mouthpiece and to use the Cyclops
- Ability to perform pulmonary function tests
- Written informed consent (child and parents)
Exclusion criteria
- Acute exacerbation
- FEV1 < 60%
- Subjects with known or suspected renal, auditory, vestibular of neuromuscular
dysfunction, or with severe, active haemoptysis
- History of adverse events on previous tobramycin or other amino glycoside use
- History of adverse events on previous dry powder inhalation
- Concurrent use of cyclosporine, amphotericin B, cephalosporins, polymyxins,
vancomycin and NSAID*s
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-005014-21-NL |
| CCMO | NL60250.000.17 |