The purpose of this study is to evaluate whether aztreonam solution for inhalation (AZLI) is safe and effective for the treatment and complete eradication of a lung infection with PA (Pseudomonas aeruginosa) in patients with Cystic Fibrosis (CF) and…
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Brief title
Condition
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to evaluate the proportion of subjects
with PA-negative cultures at all time points during a 6-month monitoring period
(through Day 196) after cessation of active treatment; microbiological cultures
will be obtained at Baseline, Day 28 (end of treatment), Day 56 (1 month after
completing AZLI), Day 112 (3 months after completing AZLI), and Day 196 (6
months after completing AZLI). PA-specific antibody titers will be obtained at
Baseline, Day 28, and Day 196.
Secondary outcome
Secondary objectives are to evaluate the following:
In subjects >= 6 years of age:
• Change from baseline in FEV1 % predicted at Days 28, 56, 112, and 196;
• Change from baseline in CFQ-R Respiratory Symptoms Score (RSS) at Days 28,
56, 112, and 196.
In all patients:
• Proportion of patients with PA-negative cultures at Days 28, 56, 112 and 196;
• Use of additional (non-study) antipseudomonal antibiotics (as a marker for PA
exacerbation);
• Change from baseline in weight, height, and body mass index (BMI) at Days 28,
56, 112, and 196;
In patients < 6 years of age:
• Pharmacokinetics: 1 peak plasma sample will be obtained 1 hour after the
first dose of AZLI (Day 1); 1 trough plasma sample will be obtained immediately
prior to the last dose of AZLI (Day 28). Plasma aztreonam concentrations at
each time point will be summarized (mean, median, standard deviation [SD],
minimum, maximum, and number of samples).
Background summary
Cystic fibrosis (CF) affects an estimated 100,000 people worldwide. In Europe,
approximately 29,000 people are estimated to have CF. Approximately 66% of
European patients are conservatively estimated to be children (< 18 years of
age). CF patients are particularly susceptible to pulmonary infections with
organisms such as Pseudomonas aeruginosa (PA), Staphylococcus aureus,
Achromobacter species (spp.), Burkholderia spp., Stenotrophomonas maltophilia,
and Haemophilus influenzae. Infected patients experience progressive
obstruction of the airways and loss of lung function that is due in large part
to the inflammatory response to chronic bacterial infection. The most
significant bacterial pathogen associated with CF pulmonary disease is PA.
PA infection is a significant predictor of mortality and has also been
associated with higher rates of pulmonary function decline. In general,
pediatric CF patients have a lower incidence of PA airway infection compared to
adults.
Initial infection with PA, prior to the development of chronic infection, has
been characterized as a window of opportunity for PA eradication. Early and
aggressive antibiotic treatment of initial PA infection in young patients with
CF has been observed to improve pulmonary function and delay the onset of
chronic PA infection, thus increasing survival. As a result, eradication of PA
at initial detection is now a treatment strategy used by most CF centers.
Study objective
The purpose of this study is to evaluate whether aztreonam solution for
inhalation (AZLI) is safe and effective for the treatment and complete
eradication of a lung infection with PA (Pseudomonas aeruginosa) in patients
with Cystic Fibrosis (CF) and who are younger than 18 years. People with CF
often have lung infections that occur repeatedly and get worse over time. The
current treatment with an antibiotic is used to stop or slow down the growth of
these bacteria. However the bacterium is not eradicated. The antibiotic may be
given orally or i.v., or in the form of an inhalation.
AZLI is an investigative drug for people under the age of 18.
AZLI is registered under the name Cayston ® in Europe and is approved for
patients aged 18 years and older who have CF and a lung infection with PA.
Study design
This is an open-label, multi-center study in children (3 months to less than 18
years) with CF and a first fixed lung infection with PA who will be treated 28
days with AZLI inhalation, 3 times daily 75 mg. Participants are followed-up
for 6 months after the treatment phase of 28 days to determine whether the PA
infection is completely eradicated.
Control visits take place at 4 different timepoints, day 28, day 56, day 112
and day 196. For all subjects blood samples will be taken at visits 2, 3 and 6
and sputum samples will be taken at visits 2, 3, 4, 5 and 6 (or throat swab if
sputum cannot be produced). If < 6 years, plasma PK samples will be taken at
visits 2 and 3. If 6 years or more, spirometry will be done at all visits. For
females of child-bearing potential, urine pregnancy tests will be taken at
visits 1, 2, 3 and 4.
The screening phase is variable up to 14 days.
It is possible to complete screening and baseline visits on one day. The
maximum duration of the study for participants is approximately 7 months (28
weeks).
AZLI will be taken using the Investigational eFlow® Nebulizer System (eFlow),
which is CE marked in the EU and marketed for use with Cayston under the trade
name Altera. The eFlow is a reusable device that mixes air with the study drug
solution so that it becomes a mist that is inhaled (breathed in). The device
works using a porous membrane (thin metal layer with many holes) that vibrates
and allows you to inhale AZLI into your lungs. This helps lessen the amount of
drug left in your mouth and throat. AZLI should only be taken using the
eFlow. The eFlow must not be used to take any other medication.
Intervention
All patients receive 28 days Aztreonam for inhalation, three times daily 75 Mgr.
Depending on the follow-up visit this may be extended up to 32 days.
Study burden and risks
Patients are asked to inhale study medication (AZLI) for 28 days, 3 times a
day. Prior to this inhalation a short-acting brochodilatator should be used,
which is not always the standard treatment for the patient.
The patient must visit the hospital at least 5 times for follow-up of the
study. Each visit will take approximately 3-4 hours.
Besides taking blood samples, completing questionnaires, also **a spirometry
could be performed (> 6 years).
Patients who are sexually active must comply with stringent precautions and
girls are regularly carried out a pregnancy test.
199 East Blaine Street -
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199 East Blaine Street -
Seattle 98102
US
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Age
Inclusion criteria
• Aged 3 months to less than 18 years.;• Diagnosis of CF as determined by the 1997 CF Consensus Conference criteria: sweat chloride level >= 60 mEq/L by quantitative pilocarpine iontophoresis; or a genotype with 2 identifiable mutations consistent with CF; or an abnormal nasal transepithelial potential difference (NPD), and 1 or more;clinical features consistent with CF.;• Documented new onset of positive lower respiratory tract culture for PA within 30 days of study entry (screening visit) defined as either first lifetime documented PA-positive culture, or PA recovered after at least a 2-year history of PA-negative respiratory cultures (at least 2 cultures per year);• FEV1 >= 80% predicted (for subjects >= 6 years of age).;• Clinically stable with no evidence of significant respiratory symptoms or, if obtained for clinical evaluation, no chest radiograph findings at screening that would require administration of IV antipseudomonal antibiotics, oxygen supplementation, or hospitalization.
Exclusion criteria
• Use of IV or inhaled antipseudomonal antibiotics within 2 years of study entry (screening visit).;• Use of oral antipseudomonal antibiotics within 30 days of study entry (screening visit).;• History of hypersensitivity/adverse reaction to aztreonam, or beta-agonists.;• Use of any investigational drug, or device within 28 days of study entry (screening visit).;• Presence of a condition or abnormality that would compromise the subject*s safety or the quality of study data, in the opinion of the investigator.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-001255-36-NL |
| CCMO | NL37691.041.11 |